Vasodilatory action of the calcium antagonist amlodipine on large and resistance pulmonary arteries from normoxic and chronically hypoxic rats.
1. Isolated rat aorta and pulmonary arteries were maximally precontracted with 100 mmol/l KCl, and the vasorelaxation due to the dihydropyridine calcium antagonist amlodipine was measured. The response of large pulmonary arteries (mean lumen diameter 983 microns) was directly compared with that of isolated pulmonary resistance vessels (mean lumen diameter 259 microns) from both normoxic animals and animals exposed to chronic hypoxia. 2. Amlodipine caused a significant relaxation of aorta (P < 0.001). A significant relaxation of large and resistance pulmonary arteries from both normoxic and chronically hypoxic animals was also demonstrated at all doses tested (P < 0.05) or less). 3. Amlodipine produced significantly more relaxation in pulmonary resistance vessels than in large pulmonary arteries from both normoxic and chronically hypoxic rats (P < 0.02). 4. The action of amlodipine was slow in onset and persistent in all vessels studied. In the pulmonary vessels from normoxic animals both the rate of onset and the magnitude of effect was proportional to the drug concentration (P < 0.001). 5. These results demonstrate that amlodipine is a potent inhibitor of KCl-induced contractions in rat pulmonary arteries with a preferential action in pulmonary resistance vessels.
Woodmansey
P A
PA
University Department of Medicine, Royal Hallamshire Hospital, Sheffield, U.K.
Zhang
F
F
Channer
K S
KS
Morice
A H
AH
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011189:Potassium Chloride; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation
D017311:Amlodipine; D011189:Potassium Chloride