Effects of the stretching on the vasoconstriction modulated by the endothelium in renal hypertensive rat aorta and coronary arteries

• Grant number: 15/17080-2
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2016 - January 31, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Lusiane Maria Bendhack
• Grantee: Lusiane Maria Bendhack
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The endothelial dysfunction described in hypertensive subjects has been characterized by reduced endothelium-dependent vasodilatation. However, its role on the contractile response is not clear. The impaired production of relaxing factors, such as Nitric Oxide (NO) and Prostacyclin (PGI2), and contractile factor Thromboxane A2 (TXA2) derived from the endothelium can contribute to endothelial dysfunction that has been associated to high production of reactive oxygen species (ROS). Preliminary results indicate that the contractile response induced by phenylephrine (PE) is lower in intact endothelium aorta (E+) from hypertensive rat (2K-1C) than in normotensive rat aorta (2K) under resting tension of 1,5 g. In 2K-1C aorta, this response is due to high H2O2 production that induces eNOS Ser1177 phosphorylation and increased NO production. Although COX activity is also increased in 2K-1C E+, NO effect is higher in 2K-1C E+ than in 2R E+ under 1,5 g resting tension. However, the contractile response induced by PE is increased in 2K-1C E+ under resting tension of 3.0 g but not in 2K E+. It suggests that the blood pressure intensity can modify the cellular signaling due to high radial vascular stretching. It might modulate the endothelial eNOS and COX activity. Therefore, the aim of the present work is to evaluate the role of the arterial blood pressure and radial vascular stretching on endothelial eNOS and COX activity to the contractile responses in aorta (phenylephrine) and coronary artery (TP prostanoid agonist) from 2K and 2K-1C rats. Furthermore, we will evaluate the vasodilatation induced by acetylcholine and by the NO donor combined with COX inhibitor indomethacin (NCX2121) in aorta and coronary arteries from 2K and 2K-1C rats.Key Words: Endothelial dysfunction, vascular stretching, renovascular hypertension, vasoconstriction, vasodilation, nitric oxide, eNOS, COX (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVA, B. R.; PERNOMIAN, L.; DE PAULA, T. D.; GRANDO, M. D.; BENDHACK, L. M.. Endothelial nitric oxide synthase and cyclooxygenase are activated by hydrogen peroxide in renal hypertensive rat aorta. European Journal of Pharmacology, v. 814, p. 87-94, NOV 5 2017. (15/17080-2)

POTJE, SIMONE R.; TROIANO, JESSICA A.; GRANDO, MARCELLA D.; GRATON, MURILO E.; DA SILVA, ROBERTO S.; BENDHACK, LUSIANE M.; ANTONIALI, CRISTINA. Endothelial modulation of a nitric oxide donor complex-induced relaxation in normotensive and spontaneously hypertensive rats. Life Sciences, v. 201, p. 130-140, MAY 15 2018. (15/17080-2, 12/20398-6, 11/20998-0)

PAULA, T. D.; SILVA, B. R.; GRANDO, M. D.; SOUZA, H. C. D.; BENDHACK, L. M.. Activation of TP receptors induces high release of PGI(2) in coronary arteries of renal hypertensive rats. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, v. 122, p. 125-133, SEP 2018. (15/00658-1, 15/17080-2)

DE PAULA, TIAGO DAL-CIN; SILVA, BRUNO R.; GRANDO, MARCELLA D.; PERNOMIAN, LAENA; DO PRADO, ALEJANDRO FERRAZ; BENDHACK, LUSIANE MARIA. Relaxation induced by the nitric oxide donor and cyclooxygenase inhibitor NCX2121 in renal hypertensive rat aortas. European Journal of Pharmaceutical Sciences, v. 107, p. 45-53, SEP 30 2017. (15/17080-2)