Effects of calcium channel blockade on renal vascular resistance responses to changes in perfusion pressure and angiotensin-converting enzyme inhibition in dogs.
We conducted these experiments to evaluate the selectivity of calcium channel blockade on the renal autoregulatory mechanism and on angiotensin II-mediated renal vasoconstriction. Experiments were performed in anesthetized dogs in which renal arterial pressure, renal blood flow, and glomerular filtration rate were measured at normal and reduced renal arterial pressure. At control arterial pressures, renal arterial infusions of verapamil increased renal blood flow and glomerular filtration rate significantly. The decreases in renal vascular resistance elicited with verapamil (n = 13) and nifedipine (n = 4) occurred only at renal arterial pressure levels within the normal autoregulatory range. Renal blood flow autoregulatory efficiency was markedly attenuated, and the pressure-flow relationship obtained during calcium channel blockade approached that of a passive system. Systemic infusions of an angiotensin-converting enzyme inhibitor (captopril) during continued verapamil infusion caused further vasodilation at all renal arterial pressure values, as evidenced by an increase in slope of 27% of the pressure-blood flow relationship. This response was reversed by angiotensin II infusions. This shift indicates a reduction in minimal vascular resistance elicited by captopril, not obtainable with verapamil alone, and sensitive to angiotensin II. The effects of verapamil and nifedipine on renal blood flow autoregulation suggest a specific effect at preglomerular sites of potential operated membrane calcium channels in the autoregulatory phenomenon. The additional vasodilation elicited with captopril and reversed by angiotensin II indicates the presence of an angiotensin-sensitive postglomerular resistance component which is not influenced by calcium entry blockers.
D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D005260:Female; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D000804:Angiotensin II; D002216:Captopril; D014700:Verapamil; D009543:Nifedipine