Recently, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. This study examined the effects of the novel dihydropyridine amlodipine on the hemodynamic response of the isolated perfused kidney to angiotensin II. Amlodipine completely reversed the angiotensin II-induced decrement in glomerular filtration rate of this model (0.72 +/- 0.15, 0.26 +/- 0.10 and 0.73 +/- 0.12 ml/min/g for control, angiotensin II and angiotensin II plus 0.1 microM amlodipine respectively). In contrast, amlodipine only partially restored renal perfusate flow (35.8 +/- 2.7, 14.7 +/- 1.9 and 23.7 +/- 2.5 ml/min/g for control, angiotensin II and angiotensin II plus amlodipine), thereby increasing filtration fraction. These findings are consistent with previous observations from this laboratory indicating that dihydropyridines predominantly vasodilate preglomerular renal resistance vessels and through this mechanism exert a preferential augmentation of glomerular filtration rate.
