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

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.

Venous endothelial function in cardiovascular disease

“…Recently, Chies et al [ 85 ] using femoral veins isolated from rats with renovascular hypertension 2K1C, reported different local mechanisms acting in a coordinated manner to mitigate Ang II responses [ 85 ]. Once again, Ang II induced very small contractile responses in femoral veins of 2K1C compared with normotensive rats.…”

“…Once again, Ang II induced very small contractile responses in femoral veins of 2K1C compared with normotensive rats. However, this lower Ang II-induced contraction was maintained in rings pre-incubated with a non-selective COX inhibitor, while the non-selective NO synthase inhibitor increased this response about three times in hypertensive vein [ 85 ]. These data suggest that NO appears to be pivotal in the modulation of Ang II responses in femoral veins of 2K1C hypertensive rats, without COX metabolites contribution [ 85 ].…”

“…However, this lower Ang II-induced contraction was maintained in rings pre-incubated with a non-selective COX inhibitor, while the non-selective NO synthase inhibitor increased this response about three times in hypertensive vein [ 85 ]. These data suggest that NO appears to be pivotal in the modulation of Ang II responses in femoral veins of 2K1C hypertensive rats, without COX metabolites contribution [ 85 ]. Together, these findings demonstrate that similarly to what occurs in the veins of normotensive animals, a complex network of local mechanisms, mainly involving NO and COX metabolites, keeps Ang II responses under constant modulation in the venous system depending on the vein segment studied as well as the animal model of hypertension used.…”