Increased relaxation by felodipine on pulmonary artery from rats with monocrotaline-induced pulmonary hypertension does not reflect functional impairment of the endothelium.
The effects of the calcium entry blocking drug, felodipine, were examined against the spasmogens, noradrenaline, 5-hydroxytryptamine (5-HT) and endothelin on pulmonary artery preparations taken from rats treated with saline or monocrotaline (endothelium present) and from untreated rats (endothelium removed). In saline-treated rats, the potencies (negative log EC50) of noradrenaline, 5-HT and endothelin were 7.97, 5.25 and 8.39 respectively, and felodipine (10 nM) reduced the maximum responses to noradrenaline (28% reduction) and 5-HT (47% reduction), without reducing their potency. In monocrotaline-treated rats, the potencies of noradrenaline, 5-HT and endothelin were 8.43, 6.42 and 8.44, and felodipine significantly reduced the potencies of noradrenaline (0.60 log units) and 5-HT (0.48 log units) in addition to reducing their maximum responses (60% and 69% reductions, respectively). Felodipine had no effect on endothelin in either group of rats. Removal of the endothelium caused a small increase in the potency of 5-HT, but had no influence on the other spasmogens or on the effects of felodipine. It is concluded that monocrotaline treatment of rats leads to increases in a) the potencies of noradrenaline and 5-HT on pulmonary artery, and b) the effectiveness of felodipine against these two spasmogens. Neither of these increases can be attributed to monocrotaline-induced endothelial cell damage.
Wanstall
J C
JC
Department of Physiology and Pharmacology, University of Queensland, Australia.
O'Donnell
S R
SR
Kay
C S
CS
D000818:Animals; D004347:Drug Interactions; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D015736:Felodipine / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology
D016232:Endothelins; D012701:Serotonin; D016686:Monocrotaline; D015736:Felodipine; D009638:Norepinephrine