Antivasoconstrictor effects of isradipine. A quantitative approach in anesthetized rats and conscious rabbits.
Calcium antagonists blunt the constrictor effects of vasoconstrictor agents. Differences in the sensitivity of several vasoconstrictors to the constrictor effect of calcium antagonists were quantified in experiments on rats and rabbits. In rats, the dose-response curves for pressor effects to angiotensin II were shifted in parallel to the right after treatment with isradipine, but not with prazosin and dihydralazine, suggesting that the antivasoconstrictor effect of isradipine was of a specific type. Blood pressure increases elicited by angiotension II or norepinephrine (alone, or with propranolol or propranolol plus prazosin) were also measured in rabbits and, again, isradipine caused parallel shifts of the dose-response curves. Both agonists thus appear to stimulate calcium entry, at least in resistance vessels, and via the same pathway, the L-type calcium channel. However, the angiotension II pressor effects were more sensitive to isradipine than those of norepinephrine in the presence of propranolol, and even more so in the presence of propranolol plus prazosin. These results suggest subtle and as yet unexplained differences, possible related to the activity of the adenylate cyclase system, in the chain of events leading to activation of the L-channels in vivo.
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Cardiovascular Unit of Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Rüegg
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D000768:Anesthesia, General; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D017275:Isradipine; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D011725:Pyridines; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009638:Norepinephrine; D017275:Isradipine