Caveolae Dysfunction Contributes to Impaired Relaxation Induced by Nitric Oxide Donor in Aorta from Renal Hypertensive Rats

Abstract

Relaxation induced by nitric oxide (NO) donors is impaired in renal hypertensive two kidney-one clip (2K-1C) rat aortas. It has been proposed that caveolae are important in signal transduction and Ca 2ϩ homeostasis. Therefore, in the present study we investigate the integrity of caveolae in vascular smooth muscle cells (VSMCs), as well as their influence on the effects produced by NO released from both the new NO donor [Ru(NH.NHq) (terpy)NO ϩ ] 3ϩ (TERPY) and sodium nitroprusside (SNP) on 2K-1C rat aorta. The potency of both TERPY and SNP was lower in the 2K-1C aorta that in the normotensive aorta [two kidney (2K)], whereas the maximal relaxant effect (ME) was similar in both 2K-1C and 2K aortas. In the 2K aorta, methyl-␤-cyclodextrin (CD) reduced both the potency of TERPY and SNP, and their ME compared with the control, but it had no effect on the potency and ME of these NO donors in 2K-1C aortas. The decrease in cytosolic Ca 2ϩ concentration ([Ca 2ϩ ] c ) induced by TERPY was larger in 2K than in 2K-1C cells, and this effect was inhibited by CD in 2K cells only. Aortic VSMCs from 2K rats presented a larger number of caveolae than those from 2K-1C rats. Treatment with CD reduced the number of caveolae in both 2K and 2K-1C aortic VSMCs. Our results support the idea that caveolae play a critical role in the relaxant effect and in the decrease in [Ca 2ϩ

Antioxidant Treatment With Tempol and Apocynin Prevents Endothelial Dysfunction and Development of Renovascular Hypertension

“…This result is consistent with previous findings showing decreased responses to NO donors in 2K-1C rat vessels. 4,41,42 In the studies cited, experiments were performed 6 weeks after surgery, the same interval as in our study. The findings suggest that the degree of smooth muscle dysfunction seems to be lower and appear later than endothelial dysfunction.…”

Mechanisms underlying the hypotensive and vasodilator effects of Ru(terpy)(bdq)NO]3+, a nitric oxide donor, differ between normotensive and spontaneously hypertensive rats

“…However, vasodilation induced by these agents differs in the experimental models of hypertension. In renal hypertensive rats, TERPY-induced vasodilation is impaired when compared with 2-kidney sham-operated rats (Rodrigues et al, 2007Bonaventura et al, 2011). However, in spontaneously hypertensive rats it is not altered as compared with normotensive Wistar rats (Munhoz et al, 2012).…”

Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds

“…These ruthenium complexes were able to elicit aortic vasodilatation in physiological conditions (4,15,16). The mechanism of vasodilatation promoted by ruthenium compounds has been attributed to NO release (18) and its action on smooth muscle cells, including sGC (16,19) and K + channel (4,16,19) activation, which in turn prompt decreased cytosolic calcium concentration (7,18,20,21) and finally aorta relaxation.…”