Modification of the renal hemodynamic response to vasoconstrictors by calcium antagonists.
Theoretical considerations suggest that the renal response to calcium antagonists may vary depending on the factors influencing basal vascular tone. Studies were conducted using the isolated perfused rat kidney to determine the response to calcium antagonists under conditions in which the determinants of renal vascular tone were accurately defined. With this model, calcium antagonists elicit vasodilation only in the presence of a vasoconstrictor. In this setting, however, the degree of vasodilation elicited depends on the nature of the vasoconstrictor employed. Thus, the reduction in renal perfusate flow (RPF) elicited by KCl-induced depolarization was completely reversed by the calcium antagonist, nitrendipine. In contrast, identical levels of vasoconstriction elicited by norepinephrine or angiotensin II were only partially reversed, suggesting that these agonists activate the renal vasculature by mechanisms that are more complex than membrane depolarization. Examination of the response of glomerular filtration rate (GFR) revealed that in the presence of norepinephrine and angiotensin II, nitrendipine exerted a preferential augmentation of GFR. Thus, concentrations that produced only modest effects on RPF increased GFR to levels equal to or exceeding control values. This selective augmentation of GFR did not occur during the renal vasoconstriction elicited by KCl. It is proposed that renal microvessels exhibit regional heterogeneity in regard to activation mechanisms and sensitivity to calcium antagonists. Calcium antagonists may selectively attenuate agonist-induced vasoconstriction of preglomerular vessels.
Nephrology Section, Veterans Administration Medical Center, Miami, Fla.
R
R
Loutzenhiser
M
M
Epstein
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004347:Drug Interactions; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D010477:Perfusion; D011673:Pulsatile Flow / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014662:Vasoconstrictor Agents