NO donors-relaxation is impaired in aorta from hypertensive rats due to a reduced involvement of K+ channels and sarcoplasmic reticulum Ca2+-ATPase

Aims: To examine the vasodilatation induce by the NO donors, [Ru(terpy)(bdg)NO](3+) (TERPY) and sodium nitroprusside (SNP), and to compare their effects in aortic rings from hypertensive 2K-1C and normotensive 2K rats. Main methods: Vascular reactivity was performed in aortic rings pre-contracted with phenylephrine (Phe 100 nM). We have analyzed the maximal relaxation (Emax) and potency (pD(2)) of NO donors. Key findings: Potency of SNP was greater than TERPY in both arterial groups. The vasodilatation induced by TERPY was greater in 2K than in 2K-1C, and it was inhibited by sGC inhibitor ODQin 2K and in 2K-1C aortic rings. ODQ did not alter the efficacy to SNP, but it reduced its potency in 2K and 2K-1C. The blockade of K+ channels reduced the potency of TERPY only in aortic rings of 2K. On the other hand, the potency of SNP was reduced in both 2K and 2K-1C. The combination of ODQ and TEA reduced the relaxation induced by TERPY and SNP in 2K and reduced the efficacy to SNP in 2K-1C aortic rings but it had no additional effect on the TERPY relaxation in 2K-1C aortas. The production of cGMP induced by TERPY was greater than that produced by SNP, which was similarly increased in 2K and 2K-1C. Sarcoplasmic reticulum Ca-ATPase inhibition only impaired the relaxation induced by SNP in 2K aortic rings. Significance: Taken together, our results provide evidences that in this model of hypertension, impaired K+ channels activation by TERPY and SERCA activation by SNP may contribute to decreased vasodilatation. (C) 2011 Elsevier Inc. All rights reserved.