Endothelin and 5-hydroxytryptamine on rat pulmonary artery in pulmonary hypertension.
Contractile responses to endothelin, 5-hydroxytryptamine (5-HT), noradrenaline and potassium were obtained on isolated preparations of pulmonary artery from rats made pulmonary hypertensive by an injection of monocrotaline (105 mg/kg s.c.) 4 weeks previously. When compared with data obtained in control rats, the potencies (negative log EC50 values) for 5-HT, noradrenaline and potassium were increased (30, 3- and 3-fold, respectively), and the maximum contractions (mN/mm2) to endothelin, noradrenaline and potassium were reduced (65, 40 and 45% reduction). These changes were not seen 2 weeks after injection of monocrotaline, before pulmonary hypertension developed, or in preparations of aorta. It is concluded that monocrotaline-induced pulmonary hypertension affects pulmonary vascular responsiveness to spasmogens differentially. The comparative importance of endothelin and 5-HT as pulmonary vasoconstrictors may change in monocrotaline-induced pulmonary hypertension, there being an increase in responsiveness to 5-HT and a decrease in responsiveness to endothelin.
Wanstall
J C
JC
Department of Physiology and Pharmacology, Brisbane, Australia.
O'Donnell
S R
SR
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016232:Endothelins; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D016686:Monocrotaline; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D011763:Pyrrolizidine Alkaloids / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*
D016232:Endothelins; D010455:Peptides; D011763:Pyrrolizidine Alkaloids; D012701:Serotonin; D011189:Potassium Chloride; D016686:Monocrotaline; D000109:Acetylcholine; D009638:Norepinephrine