Exercise-Induced Modulation of Angiotensin II Responses in Femoral Veins From 2-Kidney-1-Clip Hypertensive Rats.

Agnaldo Bruno Chies,Talita De Mello Santos,Maria Angélica Spadella,Dulce Elena Casarini,Raquel Fantin Domeniconi,Priscila Ramos De Oliveira,Roseli Peres Moreira,Luis Gabriel Navar,Carla B Rosales

doi:10.3389/fphys.2021.620438

Abstract

The present study investigated the angiotensin II (Ang II) responses in rat femoral veins taken from 2-kidney-1clip (2K1C) hypertensive rats at 4 weeks after clipping, as well as the effects of exercise on these responses. In this manner, femoral veins taken from 2K1C rats kept at rest or exposed to acute exercise or to exercise training were challenged with Ang II or endothelin-1 (ET-1) in organ bath. Simultaneously, the presence of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were determined in these preparations by western blotting. In these experiments, femoral veins exhibited subdued Ang II responses. However, after nitric oxide (NO) synthesis blockade, the responses were higher in the femoral veins taken from animals kept at rest [0.137(0.049–0.245); n = 10] than those obtained in trained animals kept at rest [0.008(0.001–0.041); n = 10] or studied after a single bout of exercise [0.001(0.001–0.054); n = 11]. In preparations in which, in addition to NO synthesis, both the local production of prostanoids and the action of ET-1 on type A (ETA) or B (ETB) receptors were inhibited, the differences induced by exercise were no longer observed. In addition, neither ET-1 responses nor the presence of COX-1 and COX-2 in these preparations were modified by the employed exercise protocols. In conclusion, NO maintains Ang II responses reduced in femoral veins of 2K1C animals at rest. However, vasodilator prostanoids as well as other relaxing mechanisms, activated by ETB stimulation, are mobilized by exercise to cooperate with NO in order to maintain controlled Ang II responses in femoral veins.

Highlights

During exercise, there is a significant increase in metabolic demand, especially in cardiac, and working skeletal muscle (Delp and O’Leary, 2004; Duncker and Bache, 2008)
Mechanisms related to vasodilator prostanoids and/or some other vasodilator mechanism triggered by the action of ET-1 on ETB receptors (ETB) act as backup to nitric oxide (NO) in animals exposed to exercise, and maintain control of the angiotensin II (Ang II) responses in femoral veins (Chies et al, 2013)
Differences in plasma Ang II levels were not observed between 2K1C rats kept at rest and those submitted to any kind of exercise (Figure 1B)

Summary

Introduction

There is a significant increase in metabolic demand, especially in cardiac, and working skeletal muscle (Delp and O’Leary, 2004; Duncker and Bache, 2008). Venoconstriction in Exercised Hypertensive Rats redistribution may be facilitated by locally produced substances that modulate the vasomotor effects of angiotensin II (Ang II) in several vascular beds (Kashimura et al, 1995; Chies et al, 2010, 2013, 2017; Park et al, 2012). The effects of exercise upon the modulating mechanisms that regulate the vascular responses to endogenous vasoconstrictors are more clearly delineated in the arterial than in the venous beds This is an important knowledge gap considering that, at rest, about 60–80% of the blood in mammals is localized in the venous compartment and a significant part of this volume may be shifted to the heart and muscle tissue during exercise (Rothe, 1983; Pang, 2001). An uncontrolled venoconstriction could result in an increment of resistance to centripetal blood flow, impairing the venous return (Rowell, 1993)

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