Generic placeholder image

Cardiovascular & Hematological Disorders-Drug Targets

Editor-in-Chief

ISSN (Print): 1871-529X
ISSN (Online): 2212-4063

Research Article

Protective Effects of TRPV1 Activation Against Cardiac Ischemia/ Reperfusion Injury is Blunted by Diet-Induced Obesity

Author(s): Beihua Zhong, Shuangtao Ma and Donna H. Wang*

Volume 20, Issue 2, 2020

Page: [122 - 130] Pages: 9

DOI: 10.2174/1871529X19666190912152041

Abstract

Background: Activation of Transient Receptor Potential Vanilloid Subtype 1 (TRPV1) channels protects the heart from Ischemia/Reperfusion (I/R) injury through releasing Calcitonin Gene-Related Peptide (CGRP) and Substance P (SP). The current study aimed to study the cardioprotective effects of TRPV1 in obesity.

Methods: TRPV1 gene knockout (TRPV1-/-) and Wild-Type (WT) mice were Fed a High-Fat Diet (HFD) or a control diet or for 20 weeks, and then the hearts were collected for I/R injury ex vivo. The hearts were mounted on a Langendorff apparatus and subjected to ischemia (30 min) and reperfusion (40 min) after incubated with capsaicin (10 nmol/L), CGRP (0.1 μmol/L) and SP (0.1 μmol/L). Then, Coronary Flow (CF), left ventricular peak positive dP/dt (+dP/dt), Left Ventricular Developed Pressure (LVDP) and Left Ventricular End-Diastolic Pressure (LVEDP) were measured.

Results: HFD intake remarkably reduced CF, +dP/dt and LVDP and elevated LVEDP in both strains (P<0.05). Treatment with capsaicin decreased infarct size, increased CF, +dP/dt and LVDP, and decreased LVEDP in WT mice on control diet (P<0.05), but did not do so in other three groups. Treatment with CGRP and SP decreased infarct size in both strains fed with control diet (P<0.05). In contrast, not all the parameters of cardiac postischemic recovery in HFD-fed WT and TRPV1-/- mice were improved by CGRP and SP.

Conclusion: These results suggest that HFD intake impairs cardiac postischemic recovery. HFDinduced impairment of recovery is alleviated by CGRP in both strains and by SP only in TRPV1-/- mice, indicating that the effects of CGRP and SP are differentially regulated during HFD intake.

Keywords: TRPV1, obesity, ischemia/reperfusion injury, CGRP, substance P, congestive heart failure.

Graphical Abstract
[1]
Poirier, P.; Giles, T.D.; Bray, G.A.; Hong, Y.; Stern, J.S.; Pi-Sunyer, F.X.; Eckel, R.H. American Heart Association Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism.Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation, 2006, 113(6), 898-918.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.171016] [PMID: 16380542]
[2]
Logue, J.; Murray, H.M.; Welsh, P.; Shepherd, J.; Packard, C.; Macfarlane, P.; Cobbe, S.; Ford, I.; Sattar, N. Obesity is associated with fatal coronary heart disease independently of traditional risk factors and deprivation. Heart, 2011, 97(7), 564-568.
[http://dx.doi.org/10.1136/hrt.2010.211201] [PMID: 21324888]
[3]
Haddock, R.E.; Hill, C.E. Sympathetic overdrive in obesity involves purinergic hyperactivity in the resistance vasculature. J. Physiol., 2011, 589(Pt 13), 3289-3307.
[http://dx.doi.org/10.1113/jphysiol.2011.207944] [PMID: 21576274]
[4]
Grassi, G.; Seravalle, G.; Dell’oro, R. Sympathetic activation in obesity: a noninnocent bystander. Hypertension, 2010, 56(3), 338-340.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.156596] [PMID: 20625071]
[5]
Gunthorpe, M.J.; Benham, C.D.; Randall, A.; Davis, J.B. The diversity in the vanilloid (TRPV) receptor family of ion channels. Trends Pharmacol. Sci., 2002, 23(4), 183-191.
[http://dx.doi.org/10.1016/S0165-6147(02)01999-5] [PMID: 11931994]
[6]
Pan, H.L.; Chen, S.R. Sensing tissue ischemia: another new function for capsaicin receptors? Circulation, 2004, 110(13), 1826-1831.
[http://dx.doi.org/10.1161/01.CIR.0000142618.20278.7A] [PMID: 15364816]
[7]
Wang, D.H. Transient receptor potential vanilloid channels in hypertension, inflammation, and end organ damage: an imminent target of therapy for cardiovascular disease? Curr. Opin. Cardiol., 2008, 23(4), 356-363.
[http://dx.doi.org/10.1097/HCO.0b013e32830460ad] [PMID: 18520720]
[8]
Caterina, M.J.; Leffler, A.; Malmberg, A.B.; Martin, W.J.; Trafton, J.; Petersen-Zeitz, K.R.; Koltzenburg, M.; Basbaum, A.I.; Julius, D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science, 2000, 288(5464), 306-313.
[http://dx.doi.org/10.1126/science.288.5464.306] [PMID: 10764638]
[9]
Davis, J.B.; Gray, J.; Gunthorpe, M.J.; Hatcher, J.P.; Davey, P.T.; Overend, P.; Harries, M.H.; Latcham, J.; Clapham, C.; Atkinson, K.; Hughes, S.A.; Rance, K.; Grau, E.; Harper, A.J.; Pugh, P.L.; Rogers, D.C.; Bingham, S.; Randall, A.; Sheardown, S.A. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature, 2000, 405(6783), 183-187.
[http://dx.doi.org/10.1038/35012076] [PMID: 10821274]
[10]
Watson, R.E.; Supowit, S.C.; Zhao, H.; Katki, K.A.; Dipette, D.J. Role of sensory nervous system vasoactive peptides in hypertension. Braz. J. Med. Biol. Res., 2002, 35(9), 1033-1045.
[http://dx.doi.org/10.1590/S0100-879X2002000900004] [PMID: 12219175]
[11]
Zhong, B.; Wang, D.H. TRPV1 gene knockout impairs preconditioning protection against myocardial injury in isolated perfused hearts in mice. Am. J. Physiol. Heart Circ. Physiol., 2007, 293(3), H1791-H1798.
[http://dx.doi.org/10.1152/ajpheart.00169.2007] [PMID: 17586621]
[12]
Wang, L.; Wang, D.H. TRPV1 gene knockout impairs postischemic recovery in isolated perfused heart in mice. Circulation, 2005, 112(23), 3617-3623.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.105.556274] [PMID: 16314376]
[13]
Zvara, A.; Bencsik, P.; Fodor, G.; Csont, T.; Hackler, L., Jr; Dux, M.; Fürst, S.; Jancsó, G.; Puskás, L.G.; Ferdinandy, P. Capsaicin-sensitive sensory neurons regulate myocardial function and gene expression pattern of rat hearts: a DNA microarray study. FASEB J., 2006, 20(1), 160-162.
[http://dx.doi.org/10.1096/fj.05-4060fje] [PMID: 16278290]
[14]
Balakumar, P.; Singh, H.; Singh, M.; Anand-Srivastava, M.B. The impairment of preconditioning-mediated cardioprotection in pathological conditions. Pharmacol. Res., 2009, 60(1), 18-23.
[http://dx.doi.org/10.1016/j.phrs.2009.03.002] [PMID: 19427581]
[15]
Strömer, H.; Cittadini, A.; Szymanska, G.; Apstein, C.S.; Morgan, J.P. Validation of different methods to compare isovolumic cardiac function in isolated hearts of varying sizes. Am. J. Physiol., 1997, 272(1 Pt 2), H501-H510.
[PMID: 9082860]
[16]
Zhong, B.; Wang, D.H. Protease-activated receptor 2-mediated protection of myocardial ischemia-reperfusion injury: role of transient receptor potential vanilloid receptors. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2009, 297(6), R1681-R1690.
[http://dx.doi.org/10.1152/ajpregu.90746.2008] [PMID: 19812353]
[17]
Tominaga, M.; Eguchi, H.; Manaka, H.; Igarashi, K.; Kato, T.; Sekikawa, A. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care, 1999, 22(6), 920-924.
[http://dx.doi.org/10.2337/diacare.22.6.920] [PMID: 10372242]
[18]
Vogel, R.A.; Corretti, M.C.; Plotnick, G.D. Effect of a single high-fat meal on endothelial function in healthy subjects. Am. J. Cardiol., 1997, 79(3), 350-354.
[http://dx.doi.org/10.1016/S0002-9149(96)00760-6] [PMID: 9036757]
[19]
Bratz, I.N.; Dick, G.M.; Tune, J.D.; Edwards, J.M.; Neeb, Z.P.; Dincer, U.D.; Sturek, M. Impaired capsaicin-induced relaxation of coronary arteries in a porcine model of the metabolic syndrome. Am. J. Physiol. Heart Circ. Physiol., 2008, 294(6), H2489-H2496.
[http://dx.doi.org/10.1152/ajpheart.01191.2007] [PMID: 18390821]
[20]
Asimakis, G.K.; DiPette, D.J.; Conti, V.R.; Holland, O.B.; Zwischenberger, J.B. Hemodynamic action of calcitonin gene-related peptide in the isolated rat heart. Life Sci., 1987, 41(5), 597-603.
[http://dx.doi.org/10.1016/0024-3205(87)90413-9] [PMID: 3496512]
[21]
Kawasaki, H.; Takasaki, K.; Saito, A.; Goto, K. Calcitonin gene-related peptide acts as a novel vasodilator neurotransmitter in mesenteric resistance vessels of the rat. Nature, 1988, 335(6186), 164-167.
[http://dx.doi.org/10.1038/335164a0] [PMID: 2901042]
[22]
Oh-hashi, Y.; Shindo, T.; Kurihara, Y.; Imai, T.; Wang, Y.; Morita, H.; Imai, Y.; Kayaba, Y.; Nishimatsu, H.; Suematsu, Y.; Hirata, Y.; Yazaki, Y.; Nagai, R.; Kuwaki, T.; Kurihara, H. Elevated sympathetic nervous activity in mice deficient in alphaCGRP. Circ. Res., 2001, 89(11), 983-990.
[http://dx.doi.org/10.1161/hh2301.100812] [PMID: 11717154]
[23]
Ralevic, V.; Karoon, P.; Burnstock, G. Long-term sensory denervation by neonatal capsaicin treatment augments sympathetic neurotransmission in rat mesenteric arteries by increasing levels of norepinephrine and selectively enhancing postjunctional actions. J. Pharmacol. Exp. Ther., 1995, 274(1), 64-71.
[PMID: 7616449]
[24]
Brain, S.D.; Williams, T.J.; Tippins, J.R.; Morris, H.R.; MacIntyre, I. Calcitonin gene-related peptide is a potent vasodilator. Nature, 1985, 313(5997), 54-56.
[http://dx.doi.org/10.1038/313054a0] [PMID: 3917554]
[25]
Franco-Cereceda, A.; Källner, G.; Lundberg, J.M. Capsazepine-sensitive release of calcitonin gene-related peptide from C-fibre afferents in the guinea-pig heart by low pH and lactic acid. Eur. J. Pharmacol., 1993, 238(2-3), 311-316.
[http://dx.doi.org/10.1016/0014-2999(93)90862-C] [PMID: 8405099]
[26]
Marshall, I. Mechanism of vascular relaxation by the calcitonin gene-related peptide. Ann. N. Y. Acad. Sci., 1992, 657, 204-215.
[http://dx.doi.org/10.1111/j.1749-6632.1992.tb22769.x] [PMID: 1322088]
[27]
Brain, S.D.; Grant, A.D. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol. Rev., 2004, 84(3), 903-934.
[http://dx.doi.org/10.1152/physrev.00037.2003] [PMID: 15269340]
[28]
Lundberg, J.M.; Franco-Cereceda, A.; Hua, X.; Hökfelt, T.; Fischer, J.A. Co-existence of substance P and calcitonin gene-related peptide-like immunoreactivities in sensory nerves in relation to cardiovascular and bronchoconstrictor effects of capsaicin. Eur. J. Pharmacol., 1985, 108(3), 315-319.
[http://dx.doi.org/10.1016/0014-2999(85)90456-X] [PMID: 2580718]
[29]
Papka, R.E.; Urban, L. Distribution, origin and sensitivity to capsaicin of primary afferent substance P-immunoreactive nerves in the heart. Acta Physiol. Hung., 1987, 69(3-4), 459-468.
[PMID: 2444072]
[30]
Linnik, M.D.; Moskowitz, M.A. Identification of immunoreactive substance P in human and other mammalian endothelial cells. Peptides, 1989, 10(5), 957-962.
[http://dx.doi.org/10.1016/0196-9781(89)90175-7] [PMID: 2481848]
[31]
Ho, W.Z.; Lai, J.P.; Zhu, X.H.; Uvaydova, M.; Douglas, S.D. Human monocytes and macrophages express substance P and neurokinin-1 receptor. J. Immunol., 1997, 159(11), 5654-5660.
[PMID: 9548509]
[32]
Chiao, H.; Caldwell, R.W. The role of substance P in myocardial dysfunction during ischemia and reperfusion. Naunyn Schmiedebergs Arch. Pharmacol., 1996, 353(4), 400-407.
[PMID: 8935706]
[33]
Egashira, K.; Inou, T.; Yamada, A.; Hirooka, Y.; Takeshita, A. Preserved endothelium-dependent vasodilation at the vasospastic site in patients with variant angina. J. Clin. Invest., 1992, 89(3), 1047-1052.
[http://dx.doi.org/10.1172/JCI115646] [PMID: 1371774]
[34]
Pinto, F.M.; Almeida, T.A.; Hernandez, M.; Devillier, P.; Advenier, C.; Candenas, M.L. mRNA expression of tachykinins and tachykinin receptors in different human tissues. Eur. J. Pharmacol., 2004, 494(2-3), 233-239.
[http://dx.doi.org/10.1016/j.ejphar.2004.05.016] [PMID: 15212980]
[35]
Ziche, M.; Morbidelli, L.; Parenti, A.; Amerini, S.; Granger, H.J.; Maggi, C.A. Substance P increases cyclic GMP levels on coronary postcapillary venular endothelial cells. Life Sci., 1993, 53(14), PL229-PL234.
[http://dx.doi.org/10.1016/0024-3205(93)90556-I] [PMID: 7690446]
[36]
Ahluwalia, A.; Vallance, P. Evidence for functional responses to sensory nerve stimulation of rat small mesenteric veins. J. Pharmacol. Exp. Ther., 1997, 281(1), 9-14.
[PMID: 9103474]
[37]
Kummer, W.; Shigemoto, R.; Haberberger, R. Smooth muscle cells are the site of neurokinin-1 receptor localization in the arterial supply of the rat sciatic nerve. Neurosci. Lett., 1999, 259(2), 119-122.
[http://dx.doi.org/10.1016/S0304-3940(98)00926-4] [PMID: 10025572]
[38]
Powell, B.D.; Redfield, M.M.; Bybee, K.A.; Freeman, W.K.; Rihal, C.S. Association of obesity with left ventricular remodeling and diastolic dysfunction in patients without coronary artery disease. Am. J. Cardiol., 2006, 98(1), 116-120.
[http://dx.doi.org/10.1016/j.amjcard.2006.01.063] [PMID: 16784933]

© 2024 Bentham Science Publishers | Privacy Policy