Effects of isradipine and other calcium antagonists on arteriovenous-shunt flow in anesthetized rabbits and cats.
The effects of vasodilators on arteriovenous (AV)-shunt flow was investigated in anesthetized cats and rabbits, using the tracer microsphere method. In cats, the calcium antagonist isradipine reduced AV-shunt flow; verapamil showed a similar tendency and nicardipine was without effect. Dihydralazine strongly increased, but nitroglycerin and dipyridamole decreased AV-shunt flow. In rabbits, the effects of isradipine and verapamil were similar to those seen in cats. Sodium nitroprusside had no effect, whereas prazosin, minoxidil, and the potassium-channel activator cromakalim increased AV-shunt flow. The contrasting effects of drugs sharing the same mechanism of action suggest that target-tissue selectivity is more important than the mechanism of action. An increase of AV-shunt flow is unlikely to be beneficial but could be associated with a number of undesirable side effects. It might negatively affect migraine sufferers and, if AV-shunt dilatation shows no tolerance development, it represents an unnecessary hemodynamic burden for the heart.
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Cardiovascular Unit of Preclinical Research, Sandoz Ltd., Basel, Switzerland.
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001163:Arteriovenous Anastomosis / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D002415:Cats; D004305:Dose-Response Relationship, Drug; D017275:Isradipine; D008833:Microcirculation / Q000187:drug effects*; D008863:Microspheres; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D011868:Radioisotopes; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D011725:Pyridines; D011868:Radioisotopes; D014665:Vasodilator Agents; D017275:Isradipine