Hostname: page-component-7c8c6479df-995ml Total loading time: 0 Render date: 2024-03-29T05:17:16.349Z Has data issue: false hasContentIssue false

Diabetic neuropathy and heart failure: role of neuropeptides

Published online by Cambridge University Press:  10 August 2011

Asma Ejaz
Affiliation:
Department of Surgery, Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Frank W. LoGerfo
Affiliation:
Department of Surgery, Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Leena Pradhan*
Affiliation:
Department of Surgery, Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
*
*Corresponding author: Leena Pradhan, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Dana-805, Boston, MA, USA. E-mail: lpradhan@bidmc.harvard.edu

Abstract

Cardiovascular autonomic neuropathy (CAN), in which patients present with damage of autonomic nerve fibres, is one of the most common complications of diabetes. CAN leads to abnormalities in heart rate and vascular dynamics, which are features of diabetic heart failure. Dysregulated neurohormonal activation, an outcome of diabetic neuropathy, has a significant pathophysiological role in diabetes-associated cardiovascular disease. Key players in neurohormonal activation include cardioprotective neuropeptides and their receptors, such as substance P (SP), neuropeptide Y (NPY), calcitonin-gene-related peptide (CGRP), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). These neuropeptides are released from the peripheral or autonomic nervous system and have vasoactive properties. They are further implicated in cardiomyocyte hypertrophy, calcium homeostasis, ischaemia-induced angiogenesis, protein kinase C signalling and the renin–angiotensin–aldosterone system. Therefore, dysregulation of the expression of neuropeptides or activation of the neuropeptide signalling pathways can negatively affect cardiac homeostasis. Targeting neuropeptides and their signalling pathways might thus serve as new therapeutic interventions in the treatment of heart failure associated with diabetes. This review discusses how neuropeptide dysregulation in diabetes might affect cardiac functions that contribute to the development of heart failure.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Resnick, H.E. et al. (2001) Prevalence and clinical implications of American Diabetes Association-defined diabetes and other categories of glucose dysregulation in older adults: the health, aging and body composition study. Journal of Clinical Epidemiology 54, 869-876CrossRefGoogle ScholarPubMed
2Cohen-Solal, A., Beauvais, F. and Logeart, D. (2008) Heart failure and diabetes mellitus: epidemiology and management of an alarming association. Journal of Cardiac Failure 14, 615-625Google Scholar
3Giles, T.D. and Sander, G.E. (2004) Diabetes mellitus and heart failure: basic mechanisms, clinical features, and therapeutic considerations. Cardiology Clinics 22, 553-568CrossRefGoogle ScholarPubMed
4Stratton, I.M. et al. (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321, 405-412CrossRefGoogle ScholarPubMed
5Tesfaye, S. et al. (2010) Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33, 2285-2293CrossRefGoogle ScholarPubMed
6Rudy, A. (1945) Diabetic neuropathy. New England Journal of Medicine 233, 684-689Google Scholar
7Levy, D.M. et al. (1992) Immunohistochemical measurements of nerves and neuropeptides in diabetic skin: relationship to tests of neurological function. Diabetologia 35, 889-897Google Scholar
8Bolinder, J. et al. (2002) Autonomic neuropathy is associated with impaired pancreatic polypeptide and neuropeptide Y responses to insulin-induced hypoglycaemia in Type I diabetic patients. Diabetologia 45, 1043-1044Google Scholar
9Kunt, T. et al. (2000) Serum levels of substance P are decreased in patients with type 1 diabetes. Experimental and Clinical Endocrinology and Diabetes 108, 164-167CrossRefGoogle ScholarPubMed
10Ponery, E.A.a.A. (2003) Pancreatic peptides, neuropeptides and neurotransmitters in diabetes mellitus: a review. International Journal of Diabetes and Metabolism 11, 1-6Google Scholar
11McKenna, K. et al. (2000) Acute hyperglycaemia causes elevation in plasma atrial natriuretic peptide concentrations in Type 1 diabetes mellitus. Diabetic Medicine 17, 512-517CrossRefGoogle ScholarPubMed
12Ziegler, D. (1994) Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment. Diabetes/Metabolism Reviews 10, 339-383CrossRefGoogle ScholarPubMed
13Veves, A. et al. (1998) Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration. Diabetes 47, 457-463CrossRefGoogle ScholarPubMed
14Aronson, D. (2008) Hyperglycemia and the pathobiology of diabetic complications. Advances in Cardiology 45, 1-16CrossRefGoogle ScholarPubMed
15Monahan, T.S. et al. (2005) Preoperative cardiac evaluation does not improve or predict perioperative or late survival in asymptomatic diabetic patients undergoing elective infrainguinal arterial reconstruction. Journal of Vascular Surgery 41, 38-45; discussion 45Google Scholar
16Bauters, C. et al. (2003) Influence of diabetes mellitus on heart failure risk and outcome. Cardiovascular Diabetology 2, 1CrossRefGoogle ScholarPubMed
17Gheorghiade, M. and Bonow, R.O. (1998) Chronic heart failure in the United States: a manifestation of coronary artery disease. Circulation 97, 282-289CrossRefGoogle ScholarPubMed
18Orasanu, G. et al. (2008) The peroxisome proliferator-activated receptor-gamma agonist pioglitazone represses inflammation in a peroxisome proliferator-activated receptor-alpha-dependent manner in vitro and in vivo in mice. Journal of the American College of Cardiology 52, 869-881Google Scholar
19Morel, O. et al. (2010) Diabetes and the platelet: toward new therapeutic paradigms for diabetic atherothrombosis. Atherosclerosis 212, 367-376CrossRefGoogle ScholarPubMed
20Rask-Madsen, C. and King, G.L. (2007) Mechanisms of disease: endothelial dysfunction in insulin resistance and diabetes. Nature Clinical Practice. Endocrinology and Metabolism 3, 46-56CrossRefGoogle ScholarPubMed
21Hayat, S.A. et al. (2004) Diabetic cardiomyopathy: mechanisms, diagnosis and treatment. Clinical Science (London) 107, 539-557Google Scholar
22Falcao-Pires, I. and Leite-Moreira, A.F. (2011) Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment. Heart Failure Reviews [epub]Google Scholar
23Pittenger, G. and Vinik, A. (2003) Nerve growth factor and diabetic neuropathy. Experimental Diabesity Research 4, 271-285Google Scholar
24Obrosova, I.G. (2009) Diabetic painful and insensate neuropathy: pathogenesis and potential treatments. Neurotherapeutics 6, 638-647CrossRefGoogle ScholarPubMed
25Valensi, P. et al. (1997) Diabetic peripheral neuropathy: effects of age, duration of diabetes, glycemic control, and vascular factors. Journal of Diabetes and its Complications 11, 27-34CrossRefGoogle ScholarPubMed
26Dinh, T. et al. (2009) Foot muscle energy reserves in diabetic patients without and with clinical peripheral neuropathy. Diabetes Care 32, 1521-1524Google Scholar
28Krendel, D.A. (1998) Vascular inflammation in proximal diabetic neuropathy. Journal of Neurology 245, 748Google Scholar
29Said, G. (2007) Diabetic neuropathy – a review. Nature Clinical Practice. Neurology 3, 331-340CrossRefGoogle ScholarPubMed
30Pittenger, G.L. et al. (1999) Specific fiber deficits in sensorimotor diabetic polyneuropathy correspond to cytotoxicity against neuroblastoma cells of sera from patients with diabetes. Diabetes Care 22, 1839-1844CrossRefGoogle ScholarPubMed
31Veves, A. and King, G.L. (2001) Can VEGF reverse diabetic neuropathy in human subjects? Journal of Clinical Investigation 107, 1215-1218CrossRefGoogle ScholarPubMed
32Cameron, N.E. and Cotter, M.A. (1997) Metabolic and vascular factors in the pathogenesis of diabetic neuropathy. Diabetes 46 (Suppl 2), S31-S37Google Scholar
33Hoeldtke, R.D. et al. (2002) Nitrosative stress, uric Acid, and peripheral nerve function in early type 1 diabetes. Diabetes 51, 2817-2825Google Scholar
34Winkler, G. and Kempler, P. (2010) Pathomechanism of diabetic neuropathy: background of the pathogenesis-oriented therapy. Orvosi Hetilap 151, 971-981CrossRefGoogle ScholarPubMed
35Vinik, A.I. and Erbas, T. (2001) Recognizing and treating diabetic autonomic neuropathy. Cleveland Clinic Journal of Medicine 68, 928-930, 932, 934-944Google Scholar
36Vinik, A.I. et al. (2003) Diabetic autonomic neuropathy. Diabetes Care 26, 1553-1579CrossRefGoogle ScholarPubMed
37Schumer, MP, Joyner, S.A., Pfeifer, MA (1998) Cardiovascular autonomic neuropathy testing in patients with diabetes. Diabetes Spectrum 11, 227-231Google Scholar
38Ziegler, D. (1999) Cardiovascular autonomic neuropathy: clinical manifestations and measurement. Diabetes Reviews 7, 300-315Google Scholar
39Vinik, A.I. and Erbas, T. (2006) Cardiovascular autonomic neuropathy: diagnosis and management. Current Diabetes Reports 6, 424-430CrossRefGoogle ScholarPubMed
40Maser, R.E. and Lenhard, M.J. (2005) Cardiovascular autonomic neuropathy due to diabetes mellitus: clinical manifestations, consequences, and treatment. Journal of Clinical Endocrinology and Metabolism 90, 5896-5903CrossRefGoogle Scholar
41Weimer, L.H. (2010) Autonomic testing: common techniques and clinical applications. Neurologist 16, 215-222CrossRefGoogle ScholarPubMed
42Pop-Busui, R. et al. (2010) Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care 33, 1578-1584CrossRefGoogle ScholarPubMed
43Debono, M. and Cachia, E. (2007) The impact of cardiovascular autonomic neuropathy in diabetes: is it associated with left ventricular dysfunction? Autonomic Neuroscience 132, 1-7CrossRefGoogle ScholarPubMed
44Uusitupa, M.I., Mustonen, J.N. and Airaksinen, K.E. (1990) Diabetic heart muscle disease. Annals of Medicine 22, 377-386CrossRefGoogle ScholarPubMed
45Taskiran, M. et al. (2004) Left ventricular dysfunction in normotensive Type 1 diabetic patients: the impact of autonomic neuropathy. Diabetic Medicine 21, 524-530Google Scholar
46Rapacciuolo, A. et al. (2001) Important role of endogenous norepinephrine and epinephrine in the development of in vivo pressure-overload cardiac hypertrophy. Journal of the American College of Cardiology 38, 876-882CrossRefGoogle ScholarPubMed
47King, B.D. et al. (1987) Absence of hypertension despite chronic marked elevations in plasma norepinephrine in conscious dogs. Hypertension 9, 582-590CrossRefGoogle ScholarPubMed
48Pop-Busui, R. (2010) Cardiac autonomic neuropathy in diabetes: a clinical perspective. Diabetes Care 33, 434-441CrossRefGoogle ScholarPubMed
49Sundkvist, G. et al. (1992) Plasma neuropeptide Y (NPY) and galanin before and during exercise in type 1 diabetic patients with autonomic dysfunction. Diabetes Research and Clinical Practice 15, 219-226CrossRefGoogle ScholarPubMed
50El-Sayed, Z.A. et al. (2009) Cardiovascular autonomic function assessed by autonomic function tests and serum autonomic neuropeptides in Egyptian children and adolescents with rheumatic diseases. Rheumatology (Oxford) 48, 843-848Google Scholar
51Ralevic, V., Aberdeen, J.A. and Burnstock, G. (1991) Acrylamide-induced autonomic neuropathy of rat mesenteric vessels: histological and pharmacological studies. Journal of the Autonomic Nervous System 34, 77-87CrossRefGoogle ScholarPubMed
52Meit Björndahl, R.C., Luxun, X. and Yihai, C. (2006) NPY-induced Angiogenesis in Retinopathy and Wound Healing, Birkhäuser Basel, StockholmGoogle Scholar
53Chen, M. et al. (2005) Neuropeptide Y induces cardiomyocyte hypertrophy via calcineurin signaling in rats. Regulatory Peptides 125, 9-15Google Scholar
54Ekstrand, A.J. et al. (2003) Deletion of neuropeptide Y (NPY) 2 receptor in mice results in blockage of NPY-induced angiogenesis and delayed wound healing. Proceedings of the National Academy of Sciences of the United States of America 100, 6033-6038CrossRefGoogle ScholarPubMed
55Zukowska-Grojec, Z. et al. (1998) Neuropeptide Y: a novel angiogenic factor from the sympathetic nerves and endothelium. Circulation Research 83, 187-195Google Scholar
56Pradhan, L. et al. (2009) Inflammation and neuropeptides: the connection in diabetic wound healing. Expert Reviews in Molecular Medicine 11, e2CrossRefGoogle ScholarPubMed
57Jain, M. et al. (2011) Effect of hyperglycemia and neuropeptides on interleukin-8 expression and angiogenesis in dermal microvascular endothelial cells. Journal of Vascular Surgery 53, 1654-1660CrossRefGoogle ScholarPubMed
58Kim, S.Z., Cho, K.W. and Kim, S.H. (1999) Modulation of endocardial natriuretic peptide receptors in right ventricular hypertrophy. American Journal of Physiology 277, H2280-H2289Google ScholarPubMed
59Woo, N.D. and Ganguly, P.K. (1995) Neuropeptide Y prevents agonist-stimulated increases in contractility. Hypertension 26, 480-484CrossRefGoogle ScholarPubMed
60Sieburth, D., Madison, J.M. and Kaplan, J.M. (2007) PKC-1 regulates secretion of neuropeptides. Nature Neuroscience 10, 49-57CrossRefGoogle ScholarPubMed
61Hackenthal, E. et al. (1987) Neuropeptide Y inhibits renin release by a pertussis toxin-sensitive mechanism. American Journal of Physiology 252, F543-F550Google Scholar
62Blomqvist, A.G. and Herzog, H. (1997) Y-receptor subtypes – how many more? Trends in Neurosciences 20, 294-298CrossRefGoogle ScholarPubMed
63Adrian, T.E. et al. (1983) Neuropeptide Y distribution in human brain. Nature 306, 584-586Google Scholar
64Kaye, W.H. et al. (1990) Altered cerebrospinal fluid neuropeptide Y and peptide YY immunoreactivity in anorexia and bulimia nervosa. Archives of General Psychiatry 47, 548-556Google Scholar
65Zukowska, Z. et al. (2003) Neuropeptide Y: a new mediator linking sympathetic nerves, blood vessels and immune system? Canadian Journal of Physiology and Pharmacology 81, 89-94Google Scholar
66Brothers, S.P. and Wahlestedt, C. (2010) Therapeutic potential of neuropeptide Y (NPY) receptor ligands. EMBO Molecular Medicine 2, 429-439CrossRefGoogle ScholarPubMed
67Pedrazzini, T., Pralong, F. and Grouzmann, E. (2003) Neuropeptide Y: the universal soldier. Cellular and Molecular Life Sciences 60, 350-377CrossRefGoogle ScholarPubMed
68Kohno, D. et al. (2003) Ghrelin directly interacts with neuropeptide-Y-containing neurons in the rat arcuate nucleus: Ca2+ signaling via protein kinase A and N-type channel-dependent mechanisms and cross-talk with leptin and orexin. Diabetes 52, 948-956Google Scholar
69Pons, J. et al. (2008) Interactions of multiple signaling pathways in neuropeptide Y-mediated bimodal vascular smooth muscle cell growth. Canadian Journal of Physiology and Pharmacology 86, 438-448CrossRefGoogle ScholarPubMed
70Kuncova, J. et al. (2005) Heterogenous changes in neuropeptide Y, norepinephrine and epinephrine concentrations in the hearts of diabetic rats. Autonomic Neuroscience 121, 7-15CrossRefGoogle ScholarPubMed
71Watanabe, M. et al. (2008) Direct and indirect modulation of neuropeptide Y gene expression in response to hypoglycemia in rat arcuate nucleus. FEBS Letters 582, 3632-3638Google Scholar
72Andersson, D. et al. (1992) Diminished contractile responses to neuropeptide Y of arteries from diabetic rabbits. Journal of the Autonomic Nervous System 37, 215-222CrossRefGoogle ScholarPubMed
73Lind, H. et al. (1995) Selective attenuation of neuropeptide-Y-mediated contractile responses in blood vessels from patients with diabetes mellitus. Clinical Autonomic Research 5, 191-197CrossRefGoogle ScholarPubMed
74Zhang, X.M., Han, S. and Zhou, L. (2004) The investigation of Syn and NPY expression in brain tissues of diabetic model rat induced by streptozotocin. Shi Yan Sheng Wu Xue Bao 37, 449-455Google Scholar
75Matyal, R. et al. Chronic type II diabetes mellitus leads to changes in neuropeptide Y receptor expression and distribution in human myocardial tissue. European Journal of Pharmacology 665, 19-28CrossRefGoogle Scholar
76Olcese, J. (1991) Neuropeptide Y: an endogenous inhibitor of norepinephrine-stimulated melatonin secretion in the rat pineal gland. Journal of Neurochemistry 57, 943-947CrossRefGoogle ScholarPubMed
77Allen, A.R. et al. (2006) Modulation of contractile function through neuropeptide Y receptors during development of cardiomyocyte hypertrophy. Journal of Pharmacology and Experimental Therapeutics 319, 1286-1296CrossRefGoogle ScholarPubMed
78Wier, W.G. et al. (2009) Sympathetic neurogenic Ca2+ signalling in rat arteries: ATP, noradrenaline and neuropeptide Y. Experimental Physiology 94, 31-37CrossRefGoogle ScholarPubMed
79Prieto, D. et al. (2000) Neuropeptide Y regulates intracellular calcium through different signalling pathways linked to a Y(1)-receptor in rat mesenteric small arteries. British Journal of Pharmacology 129, 1689-1699Google Scholar
80Chottova Dvorakova, M. et al. (2008) Expression of neuropeptide Y and its receptors Y1 and Y2 in the rat heart and its supplying autonomic and spinal sensory ganglia in experimentally induced diabetes. Neuroscience 151, 1016-1028Google Scholar
81Woo, N.D. et al. (1994) Adrenoreceptor-mediated effect of neuropeptide Y decreases cardiac inotropic responses. Biochimica et Biophysica Acta 1222, 457-463Google Scholar
82Goldberg, Y. et al. (1998) Intracellular signaling leads to the hypertrophic effect of neuropeptide Y. American Journal of Physiology 275, C1207-C1215CrossRefGoogle Scholar
83Pellieux, C. et al. (2000) Neuropeptide Y (NPY) potentiates phenylephrine-induced mitogen-activated protein kinase activation in primary cardiomyocytes via NPY Y5 receptors. Proceedings of the National Academy of Sciences of the United States of America 97, 1595-1600Google Scholar
84Robich, M.P. et al. (2010) Effects of neuropeptide Y on collateral development in a swine model of chronic myocardial ischemia. Journal of Molecular and Cellular Cardiology 49, 1022-1030Google Scholar
85Waeber, B. et al. (1990) Role of atrial natriuretic peptides and neuropeptide Y in blood pressure regulation. Hormone Research 34, 161-165Google Scholar
86Winaver, J. and Abassi, Z. (2006) Role of neuropeptide Y in the regulation of kidney function. EXS 95, 123-132Google Scholar
87Piao, F.L. et al. (2008) Different regulation of atrial ANP release through neuropeptide Y2 and Y4 receptors. Journal of Korean Medical Science 23, 1027-1032Google Scholar
88Zelis, R. et al. (1994) Neuropeptide Y infusion decreases plasma renin activity in postmyocardial infarction rats. Journal of Cardiovascular Pharmacology 24, 896-899CrossRefGoogle ScholarPubMed
89Ohtori, S. et al. (2002) Up-regulation of substance P and NMDA receptor mRNA in dorsal horn and preganglionic sympathetic neurons during adjuvant-induced noxious stimulation in rats. Annals of Anatomy 184, 71-76Google Scholar
90Hokfelt, T. et al. (1975) Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. Brain Research 100, 235-252CrossRefGoogle ScholarPubMed
91Roth, K.A. and Gordon, J.I. (1990) Spatial differentiation of the intestinal epithelium: analysis of enteroendocrine cells containing immunoreactive serotonin, secretin, and substance P in normal and transgenic mice. Proceedings of the National Academy of Sciences of the United States of America 87, 6408-6412Google Scholar
92Nieber, K. and Oehme, P. (1982) [Substance P – a neuropeptide transmitter]. Zeitschift für die gesamte innere Medizin und ihre Grenzgebiete 37, 577-582Google ScholarPubMed
93Khawaja, A.M. and Rogers, D.F. (1996) Tachykinins: receptor to effector. International Journal of Biochemistry and Cell Biology 28, 721-738CrossRefGoogle ScholarPubMed
94Trippodo, N.C. et al. (1993) Combined inhibition of neutral endopeptidase and angiotensin converting enzyme in cardiomyopathic hamsters with compensated heart failure. Journal of Pharmacology and Experimental Therapeutics 267, 108-116Google ScholarPubMed
95Tsui, H. et al. (2007) ‘Sensing’ autoimmunity in type 1 diabetes. Trends in Molecular Medicine 13, 405-413Google Scholar
96Lindberger, M. et al. (1989) Nerve fibre studies in skin biopsies in peripheral neuropathies. I. Immunohistochemical analysis of neuropeptides in diabetes mellitus. Journal of Neurological Sciences 93, 289-296Google Scholar
97Iwasaki, H. et al. (2006) A deficiency of gastric interstitial cells of Cajal accompanied by decreased expression of neuronal nitric oxide synthase and substance P in patients with type 2 diabetes mellitus. Journal of Gastroenterology 41, 1076-1087Google Scholar
98Boer, P.A. et al. (2011) Early potential impairment of renal sensory nerves in streptozotocin-induced diabetic rats: role of neurokinin receptors. Nephrology, Dialysis, Transplantation 26, 823-832CrossRefGoogle ScholarPubMed
99Paulus, W.J. (2001) The role of nitric oxide in the failing heart. Heart Failure Reviews 6, 105-118CrossRefGoogle ScholarPubMed
100Tingberg, E. et al. (2006) Neurohumoral changes in patients with left ventricular dysfunction following acute myocardial infarction and the effect of nitrate therapy: a randomized, double-blind, placebo-controlled long-term study. Journal of Cardiovascular Pharmacology 48, 166-172CrossRefGoogle ScholarPubMed
101Pradhan, L. et al. (2011) Gene expression of pro-inflammatory cytokines and neuropeptides in diabetic wound healing. Journal of Surgical Research 167, 336-342Google Scholar
102Calderone, A. et al. (1998) Nitric oxide, atrial natriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts. Journal of Clinical Investigation 101, 812-818CrossRefGoogle ScholarPubMed
103Yu, Y. et al. (2011) Parasympathetic and substance P-immunoreactive nerve denervation in atrial fibrillation models. Cardiovascular Pathology [epub]Google Scholar
104Wang, L. and Wang, D.H. (2005) TRPV1 gene knockout impairs postischemic recovery in isolated perfused heart in mice. Circulation 112, 3617-3623CrossRefGoogle ScholarPubMed
105Wharton, J. et al. (1986) Capsaicin induces a depletion of calcitonin gene-related peptide (CGRP)-immunoreactive nerves in the cardiovascular system of the guinea pig and rat. Journal of the Autonomic Nervous System 16, 289-309CrossRefGoogle Scholar
106Ren, J.Y. et al. Cardioprotection by ischemic postconditioning is lost in isolated perfused heart from diabetic rats: involvement of transient receptor potential vanilloid 1, calcitonin gene-related peptide and substance P. Regulatory Peptides 169, 49-57CrossRefGoogle Scholar
107Yan, C., Gao, M. and Deng, Z. (1998) Study on changes of plasma substance P in essential hypertension with left ventricular hypertrophy patients and the effect of promoting blood circulation and eliminating phlegm. Zhongguo Zhong Xi Yi Jie He Za Zhi 18, 336-338Google Scholar
108Valdemarsson, S. et al. (1991) Increased plasma level of substance P in patients with severe congestive heart failure treated with ACE inhibitors. Journal of Internal Medicine 230, 325-331Google Scholar
109Dzurik, M.V. et al. (2007) Endogenous substance P modulates human cardiovascular regulation at rest and during orthostatic load. Journal of Applied Physiology 102, 2092-2097Google Scholar
110Wang, L.L. et al. (2011) Implication of Substance P in myocardial contractile function during ischemia in rats. Regulatory Peptides 167, 185-191Google Scholar
111D'Souza, M. et al. (2007) Substance P is associated with heart enlargement and apoptosis in murine dilated cardiomyopathy induced by Taenia crassiceps infection. Journal of Parasitology 93, 1121-1127Google Scholar
112Edvinsson, L. et al. (1990) Congestive heart failure: involvement of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibres. European Journal of Clinical Investigation 20, 85-89CrossRefGoogle ScholarPubMed
113Bergdahl, A. et al. (1999) Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat. Acta Physiologica Scandinavica 165, 15-23CrossRefGoogle ScholarPubMed
114Quirion, R. et al. (1992) Characterization of CGRP1 and CGRP2 receptor subtypes. Annals of the New York Academy of Sciences 657, 88-105CrossRefGoogle ScholarPubMed
115Juaneda, C., Dumont, Y. and Quirion, R. (2000) The molecular pharmacology of CGRP and related peptide receptor subtypes. Trends in Pharmacological Sciences 21, 432-438Google Scholar
116McLatchie, L.M. et al. (1998) RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393, 333-339CrossRefGoogle ScholarPubMed
117Adeghate, E. (1999) Distribution of calcitonin-gene-related peptide, neuropeptide-Y, vasoactive intestinal polypeptide, cholecystokinin-8, substance P and islet peptides in the pancreas of normal and diabetic rats. Neuropeptides 33, 227-235Google Scholar
118Saffir, A.J. (1976) Letter: clinical evaluation of a newly designed contoured toothbrush. Journal of Periodontology 47, 487CrossRefGoogle ScholarPubMed
119Parlapiano, C. et al. (1995) Calcitonin gene-related peptide in diabetes mellitus type 2: a possible etiopathogenetic role. European review for medical and pharmacological studies 17, 35-39Google ScholarPubMed
120Sun, W. et al. (2003) Intramuscular transfer of naked calcitonin gene-related peptide gene prevents autoimmune diabetes induced by multiple low-dose streptozotocin in C57BL mice. European Journal of Immunology 33, 233-242CrossRefGoogle ScholarPubMed
121Morrison, J.F., Dhanasekaran, S. and Howarth, F.C. (2008) Neuropeptide Y and CGRP concentrations in the rat tail artery: effects of age and two types of diabetes. Peptides 30, 710-714CrossRefGoogle ScholarPubMed
122Creager, M.A. et al. (2003) Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: Part I. Circulation 108, 1527-1532CrossRefGoogle ScholarPubMed
123Clementi, G. et al. (1995) Anti-inflammatory activity of amylin and CGRP in different experimental models of inflammation. Life Sciences 57, PL193-PL197CrossRefGoogle ScholarPubMed
124Wu, D. et al. (2000) Characterisation of calcitonin gene-related peptide receptors in rat atrium and vas deferens: evidence for a [Cys(Et)(2, 7)]hCGRP-preferring receptor. European Journal of Pharmacology 400, 313-319CrossRefGoogle Scholar
125Li, J. et al. (2009) Nitroglycerin protects small intestine from ischemia-reperfusion injury via NO-cGMP pathway and upregulation of alpha-CGRP. Journal of Gastrointestinal Surgery 13, 478-485Google Scholar
126Liu, N. et al. (2011) Differential effects of the calcitonin gene-related peptide on cardiac performance in acute myocardial ischemia and reperfusion in isolated rat hearts. Minerva Anestesiologica 77, 789-796Google Scholar
127Covino, E. and Spadaccio, C. (2011) Calcitonin gene related peptide: a new ally in cardiac ischemic disease. Minerva Anestesiologica 77, 763-765Google Scholar
128Mishima, T. et al. (2011) Calcitonin gene-related peptide facilitates revascularization during hindlimb ischemia in mice. American Journal of Physiology. Heart and Circulatory Physiology 300, H431-H439Google ScholarPubMed
129Levin, E.R., Gardner, D.G. and Samson, W.K. (1998) Natriuretic peptides. New England Journal of Medicine 339, 321-328Google ScholarPubMed
130Hirose, S., Hagiwara, H. and Takei, Y. (2001) Comparative molecular biology of natriuretic peptide receptors. Canadian Journal of Physiology and Pharmacology 79, 665-672CrossRefGoogle ScholarPubMed
131Barr, C.S., Rhodes, P. and Struthers, A.D. (1996) C-type natriuretic peptide. Peptides 17, 1243-1251CrossRefGoogle ScholarPubMed
132Garg, R. and Pandey, K.N. (2005) Regulation of guanylyl cyclase/natriuretic peptide receptor-A gene expression. Peptides 26, 1009-1023Google Scholar
133Nakayama, T. (2005) The genetic contribution of the natriuretic peptide system to cardiovascular diseases. Endocrine Journal 52, 11-21CrossRefGoogle ScholarPubMed
134Potter, L.R. et al. (2009) Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications. Handbook of Experimental Pharmacology, 191, 341-366Google Scholar
135Struthers, A.D. (1994) Ten years of natriuretic peptide research: a new dawn for their diagnostic and therapeutic use? BMJ 308, 1615-1619Google Scholar
136Nonoguchi, H., Sands, J.M. and Knepper, M.A. (1988) Atrial natriuretic factor inhibits vasopressin-stimulated osmotic water permeability in rat inner medullary collecting duct. Journal of Clinical Investigation 82, 1383-1390CrossRefGoogle ScholarPubMed
137Woodman, O.L. et al. (2008) Atrial natriuretic peptide prevents diabetes-induced endothelial dysfunction. Life Sciences 82, 847-854Google Scholar
138Chattington, P.D. et al. (1998) Atrial natriuretic peptide in type 2 diabetes mellitus: response to a physiological mixed meal and relationship to renal function. Diabetic Medicine 15, 375-3793.0.CO;2-N>CrossRefGoogle ScholarPubMed
139Sechi, L.A. et al. (1995) Receptors for atrial natriuretic peptide are decreased in the kidney of rats with streptozotocin-induced diabetes mellitus. Journal of Clinical Investigation 95, 2451-2457Google Scholar
140Walther, T., Schuitheiss, H.P. and Tschope, C. (2001) Impaired angiotensin II regulation of renal C-type natriuretic peptide mRNA expression in experimental diabetes mellitus. Cardiovascular Research 51, 562-566Google Scholar
141Ganguly, P.K. (1991) Role of atrial natriuretic peptide in congestive heart failure due to chronic diabetes. Canadian Journal of Cardiology 7, 275-280Google Scholar
142Bhalla, M.A. et al. (2004) Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus. Journal of the American College of Cardiology 44, 1047-1052Google Scholar
143van der Horst, I.C. et al. (2010) Neurohormonal profile of patients with heart failure and diabetes. Netherlands Heart Journal 18, 190-196Google Scholar
144Saulnier, P.J. et al. (2011) Impact of Natriuretic Peptide Clearance Receptor (NPR3) Gene Variants on Blood Pressure in Type 2 Diabetes. Diabetes Care 34, 1199-1204CrossRefGoogle ScholarPubMed
145Lainchbury, J.G. et al. (2000) Effects of natriuretic peptides on load and myocardial function in normal and heart failure dogs. American Journal of Physiology. Heart and Circulatory Physiology 278, H33-H40CrossRefGoogle ScholarPubMed
146Morishita, R. et al. (1994) Autocrine and paracrine effects of atrial natriuretic peptide gene transfer on vascular smooth muscle and endothelial cellular growth. Journal of Clinical Investigation 94, 824-829CrossRefGoogle ScholarPubMed
147Thomas, C.J., Head, G.A. and Woods, R.L. (1998) ANP and bradycardic reflexes in hypertensive rats: influence of cardiac hypertrophy. Hypertension 32, 548-555Google Scholar
148Oliver, P.M. et al. (1997) Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A. Proceedings of the National Academy of Sciences of the United States of America 94, 14730-14735Google Scholar
149Kasama, S. et al. (2008) Effect of atrial natriuretic peptide on left ventricular remodelling in patients with acute myocardial infarction. European Heart Journal 29, 1485-1494Google Scholar
150Backlund, T. et al. (2001) Dual inhibition of angiotensin converting enzyme and neutral endopeptidase by omapatrilat in rat in vivo. Pharmacological Research 44, 411-418CrossRefGoogle ScholarPubMed
151Stevens, T.L. et al. (1995) A functional role for endogenous atrial natriuretic peptide in a canine model of early left ventricular dysfunction. Journal of Clinical Investigation 95, 1101-1108CrossRefGoogle Scholar
152Lohmeier, T.E. et al. (1996) Atrial natriuretic peptide and sodium homeostasis in compensated heart failure. American Journal of Physiology 271, R1353-R1363Google ScholarPubMed
153Barrios, V. et al. (2011) Clinical applicability of B-type natriuretic peptide in patients with suspected heart failure in primary care in Spain: the PANAMA study. Expert Review of Cardiovascular Therapy 9, 579-585Google Scholar
154Nadir, M.A. et al. (2011) Meta-analysis of B-type natriuretic peptide's ability to identify stress induced myocardial ischemia. American Journal of Cardiology 107, 662-667Google Scholar
155Atisha, D. et al. (2004) A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction. American Heart Journal 148, 518-523Google Scholar
156Chen, H.H. et al. (2000) Subcutaneous administration of brain natriuretic peptide in experimental heart failure. Journal of the American College of Cardiology 36, 1706-1712CrossRefGoogle ScholarPubMed
157Baliga, V. and Sapsford, R. (2009) Review article: diabetes mellitus and heart failure–an overview of epidemiology and management. Diabetes and Vascular Disease Research 6, 164-171CrossRefGoogle Scholar

Further reading, resources and contacts

Tesfaye, S. et al. (2010) Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33, 2285-2293CrossRefGoogle ScholarPubMed
Vinik, A.I. and Erbas, T. (2006) Cardiovascular autonomic neuropathy: diagnosis and management. Current Diabeties Reports 6, 424-430CrossRefGoogle ScholarPubMed
Baliga, V. and Sapsford, R. (2009) Review article: Diabetes mellitus and heart failure–an overview of epidemiology and management. Diabetes and Vascular Disease Research 6, 164-171Google Scholar
Pradhan, L. et al. (2009) Inflammation and neuropeptides: the connection in diabetic wound healing. Expert Reviews in Molecular Medicine 11, e2Google Scholar