Unaltered endothelium-dependent modulation of contraction in the pulmonary artery of hypertensive rats

Involvement of endothelium-derived nitric oxide (EDNO) in alpha-adrenoceptor agonist-induced contractile responses was studied in isolated pulmonary arteries from Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). In the presence of propranolol, noradrenaline-induced contraction was potentiated by endothelium removal or by N-G-nitro-L-arginine (L-NOARG). The magnitude of the potentiation was independent of the noradrenaline concentration. L-NOARG also shifted the concentration-response curves for phenylephrine and methoxamine to the left and upward. Contractile responses to 2-amino-5,6,7,8,-tetrahydro-6-ethyl-4H-oxazolo-(5,4-d)-azepine-dihydrochloride (BHT-933) and 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK-14304) were augmented by L-NOARG in a concentration-dependent manner. There were no differences in the effects of L-NOARG on the contractile responses to alpha-adrenoceptor agonists between the preparations from WKY and SHRSP. Endothelium-dependent relaxation in response to acetylcholine was not impaired in the preparations from SHRSP when compared with those from WKY. These observations suggest that the contractile responses to the a, adrenoceptor agonists were depressed mainly by basally released EDNO, while the responses to the alpha(2)-adrenoceptor agonists were depressed mainly by EDNO released in response to alpha(2)-adrenoceptor stimulation. The comparable influence of the endothelium on the alpha-adrenoceptor agonist-induced contractions in the pulmonary arteries from WKY and SHRSP, which were markedly different from other arteries, could be explained by the unaltered endothelium-dependent relaxation in the preparations from SHRSP. (C) 2000 Elsevier Science B.V. All rights reserved.