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Role of Endothelial Nitric Oxide in the Response to Angiotensin II of Small Mesenteric Arteries of the Rat

R Andriantsitohaina, L Okruhlicova, S F Côrtes, G J Lagaud, V Randriamboavonjy, B Muller, J C Stoclet

J Vasc Res. Sep-Oct 1996;33(5):386-94.

PMID: 8862144

Abstract:

The role of endothelium-derived nitric oxide (NO) in the vascular contractile response to angiotensin II (Ang II) has been investigated in isolated small mesenteric resistance arteries of the rat. Both contraction and intracellular Ca2+ ion concentration ([Ca2+]i) were monitored in vessels, with and without functional endothelium, which were exposed to physiological salt solution containing 25 mM KCl. Ang II induced concentration-dependent contractile responses and increases in [Ca2+]i which, at the concentration giving the maximal response (10 nM), were not sustained in arteries with functional endothelium; however, the presence of a functional endothelium did not modify the peak responses. Ang II did not increase the cyclic guanosine 3',5'-monophosphate content of the tissue nor did it induce relaxation in arteries precontracted with 3 microM noradrenaline. The decline of the Ang II responses was suppressed by removal of the endothelium or by exposure of arteries with endothelium to either the NO synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (300 microM), or the cyclic GMP-dependent protein kinase inhibitor, Rp-8-bromoguanosine 3',5'-cyclic monophosphorothioate (30 microM). On the other hand, the NO donor SIN-1 (3-morpholino-sydnonimine, 10 microM) accelerated the decline in [Ca2+]i and contraction. These results show that endothelium-derived NO does not affect the magnitude of the phasic element of the response to Ang II, but is involved in the rapid attenuation of the tonic component. Activation of cyclic GMP-dependent protein kinase accounts for this effect of endothelium-derived NO.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP208445061 Rp-8-Br-cGMPS sodium salt Rp-8-Br-cGMPS sodium salt 208445-06-1 Price
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