Renal afferent and efferent arteriolar dilation by nilvadipine: studies in the isolated perfused hydronephrotic kidney.
Although calcium antagonists are believed to exert preferential vasodilator action on the renal preglomerular afferent arteriole, we recently demonstrated that efonidipine, a novel calcium antagonist, vasodilates both afferent and efferent arterioles. Nilvadipine also is reported to increase renal blood flow and reduce filtration fraction, suggesting indirectly afferent and efferent arteriolar vasodilation. No direct investigation, however, has been conducted examining the renal microvascular action of nilvadipine. We therefore characterized the renal microvascular reactivity to nilvadipine, by using the isolated perfused rat hydronephrotic kidney. The administration of angiotensin II (0.3 nM) caused marked vasoconstriction of afferent (from 13.5 +/- 0.6 to 9.2 +/- 0.6 microm, p < 0.01, n = 6) and efferent arterioles (from 11.5 +/- 1.0 to 7.4 +/- 0.7 microm, p < 0.01; n = 5). The subsequent addition of nilvadipine (10 nM, 100 nM, and 1 microM) caused 37 +/- 5%, 91 +/- 4%, and 95 +/- 8% reversal of afferent arteriolar constriction, respectively. Similarly, efferent arterioles manifested 59 +/- 12% reversal by 1 microM nilvadipine. Thus unlike nifedipine, which we previously reported to cause modest efferent arteriolar dilation (21 +/- 1% reversal at 1 microM), nilvadipine possesses the greater ability to dilate efferent arterioles (p < 0.01 vs. nifedipine), although both antagonists cause similar magnitudes of afferent arteriolar vasodilation. Variable effects on the efferent arteriole suggest the heterogeneity in the calcium antagonist with regard to the renal microvascular action of this agent.
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Y
Y
Ozawa
K
K
Hayashi
T
T
Nagahama
K
K
Fujiwara
S
S
Wakino
T
T
Saruta
D000758:Anesthesia; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006869:Hydronephrosis / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; C035100:nilvadipine; D000804:Angiotensin II; D009543:Nifedipine