Impaired endothelium-dependent relaxation by adrenomedullin in monocrotaline-treated rat arteries.
The effects of adrenomedullin were evaluated in isolated vascular rings from rats treated with monocrotaline (60 mg/kg, s.c.) causing pulmonary hypertension and right ventricular hypertrophy within 3 to 4 weeks. Sham animals (NaCl-treated rats) were used for comparison. The relaxing effects of adrenomedullin (10(-8) M) and acetylcholine (10(-6) M) were determined in thoracic 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 40 +/- 2%, respectively). A greater relaxation was observed in response to acetylcholine. Monocrotaline-treated rats exhibited a reduction in adrenomedullin 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 acetylcholine 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 acetylcholine on aorta was decreased at 4 weeks (36% reduction, P < 0.01 vs. sham). In this model, the adrenomedullin-induced relaxation of the pulmonary artery was impaired due to a severe endothelial dysfunction which may contribute partly to the evolving pathophysiological process.
Gout
B
B
SmithKline Beecham Laboratories Pharmaceutiques, Saint-Grégoire, France.
Quiniou
M J
MJ
Khandoudi
N
N
Le Dantec
C
C
Saïag
B
B
D000109:Acetylcholine / Q000494:pharmacology; D053607:Adrenomedullin; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D016686:Monocrotaline / Q000009:adverse effects / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin; D016686:Monocrotaline; D000109:Acetylcholine