doi: 10.1161/hy02t2.102960
(Hypertension. 2002;39:438.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
Nitric Oxide Induces Dilation of Rat Aorta via Inhibition of Rho-Kinase Signaling
From the Department of Physiology (R.C.W.), Medical College of Georgia, Augusta, and the Department of Physiology (K.C.), University of Michigan, Ann Arbor.
Correspondence to Kanchan Chitaley, Department of Physiology, Medical College of Georgia, Augusta, GA 30912-3000. E-mail kanchanc{at}umich.edu
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 (N
-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.
Key Words: muscle, smooth, vascular • vasodilation • kinase • nitric oxide
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