Nitric oxide induces dilation of rat aorta via inhibition of Rho-kinase signaling

Kanchan Chitaley, R. Clinton Webb

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

NO induces vasodilation through cGMP-dependent protein kinase-dependent and-independent mechanisms. A recent study demonstrated that recombinant cGMP-dependent protein kinase can phosphorylate the small G protein, RhoA, thus inhibiting its activity. Additionally, sodium nitroprusside was found to reverse the phenylephrine-induced translocation of RhoA, which is further indicative of the inhibition of RhoA activity. RhoA is known to be involved in the Ca2+ sensitization of vascular smooth muscle through the actions of one of its downstream effectors, Rho-kinase. This study examined whether NO endogenously induces the relaxation of intact rat aorta via the inhibition of the Rho-kinase-mediated Ca2+-sensitizing pathway. Endogenous Rho-kinase inhibitor activity was inhibited by the selective compound Y-27632. Treatment of endothelium-intact rat aorta with Y-27632 (1 μmol/L) resulted in an attenuation of maximal force generated in response to phenylephrine. In endothelium-denuded rings, however, 1 μmol/L Y-27632 was ineffective at inhibiting the phenylephrine-induced contraction. Additionally, 1 μmol/L Y-27632 was significantly less effective at inhibiting the phenylephrine-induced contraction of endothelium-intact rings in the presence of inhibitors of NO synthase or guanylate cyclase (Nω-nitro-L-arginine and 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, respectively). Interestingly, sodium nitroprusside restored the ability of 1 μmol/L Y-27632 to attenuate phenylephrine-induced contraction. Rho-kinase inhibition was also found to increase the sensitivity of the endothelium-denuded aorta to sodium nitroprusside. These data demonstrate that NO inhibits Rho-kinase activity in the intact rat aorta, supporting the hypothesis that endogenous NO-mediated vasodilation occurs through the inhibition of Rho-kinase constrictor activity in the intact rat aorta.

Original languageEnglish (US)
Pages (from-to)438-442
Number of pages5
JournalHypertension
Volume39
Issue number2 II
DOIs
StatePublished - 2002

Keywords

  • Kinase
  • Muscle, smooth, vascular
  • Nitric oxide
  • Vasodilation

ASJC Scopus subject areas

  • Internal Medicine

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