Impaired endothelium-dependent relaxation by adrenomedullin in monocrotaline-treated rat arteries

The effects of adrenomedullin were evaluated in isolated vascular rings fro m rats treated with monocrotaline (60 mg/kg, s.c.) causing pulmonary hypert ension and right ventricular hypertrophy within 3 to 4 weeks. Sham animals (NaCl-treated rats) were used for comparison. The relaxing effects of adren omedullin (10(-8) M) and acetylcholine (10(-6) M) were determined in thorac ic aorta and pulmonary artery rings precontracted with phenylephrine (10(-7 ) M). In sham animals, adrenomedullin caused significant vasorelaxation of aorta and pulmonary artery although of different amplitude (24 +/- 3% and 4 0 +/- 2%, respectively). A greater relaxation was observed in response to a cetylcholine. Monocrotaline-treated rats exhibited a reduction in adrenomed ullin relaxation in pulmonary artery (54 and 68% loss of effect, at 3 and 4 weeks, respectively, P < 0.01 vs. sham) and comparable reductions in acety lcholine responses. The decrease in adrenomedullin relaxing effect was less pronounced in aorta than in pulmonary artery, suggesting a distinct tissue sensitivity to monocrotaline. In contrast, the relaxing effect of acetylch oline on aorta was decreased at 4 weeks (36% reduction, P < 0.01 vs. sham). In this model, the adrenomedullin-induced relaxation of the pulmonary arte ry was impaired due to a severe endothelial dysfunction which may contribut e partly to the evolving pathophysiological process. (C) 1999 Elsevier Scie nce B.V. All rights reserved.