Vascular Biology |
Presented in part at the 68th Scientific Sessions of the American Heart Association, Anaheim, Calif, November 1316, 1995.
From INSERM Units 141 (C.M.B., J.B., B.I.L.) and 127 (C.H.), Institut Fédératif de Recherche Circulation, Paris, France; Centers for Experimental Therapeutics (C.M.B., P.M.V.) and Comparative Medicine (R.S.G.), Baylor College of Medicine, Houston, Tex; and Institut de Recherches International Servier (P.M.V.), Courbevoie, France.
Correspondence to Chantal M. Boulanger, PhD, INSERM Unit 141, Hôpital Lariboisière, 41, Bd de la Chapelle, F-75475, Paris Cedex 10, France. E-mail cboulang{at}infobiogen.fr
AbstractThe nitric oxide synthase (NOS) inhibitor nitro-L-arginine augmented the contractions to angiotensin (Ang) II in carotid artery rings without endothelium from spontaneously hypertensive rats (SHR) but not normotensive Wistar-Kyoto rats, suggesting the possibility of nonendothelial NOS activity in SHR arteries. In SHR artery without endothelium, the potentiation of Ang II contraction by nitro-L-arginine was prevented by L-arginine, but not by D-arginine, and was observed also in the presence of oxyhemoglobin, monomethyl-L-arginine, and 7-nitroindazole, but not in the presence of aminoguanidine. In further support of NOS activation by Ang II in nonendothelial cells, Ang II but not acetylcholine stimulated cGMP levels by 2-fold in SHR arteries without endothelium; nitro-L-arginine decreased both basal and Ang IIstimulated cGMP levels. When NOS activity in SHR arteries was measured, no calcium-independent L-citrulline formation was detectable, while up to 47% of the total calcium-dependent NOS activity was present in nonendothelial cells. Expression of neuronal NOS was revealed in the media of SHR arteries by immunohistochemistry, Western blot, and reverse transcriptasepolymerase chain reaction. Expression of this NOS isoform was greater in SHR than in Wistar-Kyoto rat preparations. Finally, endothelial NOS was observed in the endothelium, but no detectable levels of inducible NOS were found in these tissues. These results demonstrate the expression of neuronal NOS in rat vascular smooth muscle cells and its activation on stimulation by Ang II in spontaneously hypertensive, but not normotensive, animals.
Key Words: cGMP neuronal nitric oxide synthase contraction nitric oxide synthase activity AT1 receptor
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