Renal microvascular actions of calcium antagonists.
Calcium antagonists elicit vasodilation by altering the function of a specific class of potential-dependent calcium channels. These agents alter renal hemodynamics in a complex manner. Studies in the isolated perfused rat kidney demonstrate that the renal vasodilatory response to calcium antagonists varies depending on the nature of the underlying renal vasoconstriction. Thus, not all renal vasoconstrictor mechanisms are sensitive to calcium antagonists. Furthermore, in the presence of agonists such as norepinephrine or angiotensin II, calcium antagonists exert a greater effect on glomerular filtration rate than on renal perfusate flow. Direct observations of the renal microvasculature suggest that this preferential augmentation of glomerular filtration rate reflects the ability of calcium antagonists to dilate preglomerular vessels while preserving efferent arteriolar tone. Thus, under identical in vitro conditions, calcium antagonists reverse afferent (preglomerular) but not efferent (postglomerular) arteriolar vasoconstriction in isolated perfused hydronephrotic kidneys. Similarly, potassium (KCl)-induced depolarization, which directly activates potential-dependent calcium channels, preferentially constricts the afferent arteriole and produces a striking decrease in glomerular filtration rate and filtration fraction. Such observations indicate that differing activating mechanisms mediate vasoconstriction within the renal microcirculation and suggest that potential-dependent calcium channels prominently contribute to afferent, but not efferent, arteriolar vasoconstriction.
Loutzenhiser
R
R
Research Services (R151) and Nephrology Section (111C1), Veterans Administration Medical Center, Miami, FL 33125, USA.
Epstein
M
M
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000494:pharmacology; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C028429:U 44069; D013928:Thromboxane A2; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine