The renin-angiotensin system modulates the peripheral vascular effects of the calcium antagonist isradipine in anesthetized rabbits.
Dihydropyridine calcium antagonists such as isradipine (PN200-110) selectively increase blood flow to the heart, brain, and skeletal muscle. The role of the renin-angiotensin system in bringing about this pattern of selectivity was investigated in two groups of eight barbiturate-anesthetized rabbits. One group was and the other one was not pretreated with 1 mg/kg i.v. of the angiotensin converting enzyme inhibitor, spirapril. In the group with the intact renin-angiotensin system, isradipine (3 and 10 micrograms/kg i.v.) elicited the typical systemic and regional (measured with 15 micron tracer microspheres) hemodynamic effects of a noncardiodepressant dihydropyridine derivative. Inhibition of the angiotensin converting enzyme blunted the effects of isradipine on central venous pressure, cardiac output, and flow to the heart, brain, and skeletal muscle. The isradipine-induced decrease of hepatic arterial and pancreatic blood flow was prevented and a similar tendency was observed in the spleen, stomach, small intestine, cecum, and arteriovenous shunt flow, indicating that the renin-angiotensin system was totally (liver, pancreas) or partially responsible for the effects of isradipine on these vessels. The renin-angiotensin system thus counteracts the dilator effect of calcium antagonists in angiotensin II sensitive vascular beds and participates in bringing about the typical pattern of regional vasodilation of these agents.
Hof
R P
RP
Cardiovascular Unit of Preclinical Research, Sandoz, Ltd., Basel, Switzerland.
Hof
A
A
D000758:Anesthesia; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D017275:Isradipine; D009200:Myocardial Contraction / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects*; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D011725:Pyridines; D012083:Renin; D017275:Isradipine