The present studies were conducted to: a) comparatively evaluate the effects of
clevidipine, a new
dihydropyridine calcium antagonist, and
fenoldopam, a
dopamine (D-1) receptor agonist on basal renal function, and b) to determine the efficacy of these agents in protecting renal function in an experimental model of
ischemia/reperfusion (I/R) induced
acute renal failure in rats. Infusions of either
clevidipine or
fenoldopam (5.0 nmol/kg(-1) min(-1) i.v. for 60 min) produced significant increases in urine flow (UV), urinary
sodium excretion (UNaV), and fractional excretion of
sodium (FENa) in
inactin anesthetized rats. Unlike
clevidipine,
fenoldopam also produced significant increases in renal blood flow (RBF) and urinary
potassium excretion (UKV). In a separate series, unilateral
renal failure was induced in anesthetized rats by occluding the left renal artery for 40 min followed by reperfusion. In this model, there was a 70-75% reduction in the GFR that was paradoxically associated with several fold increases in UV, UNaV, and FENa in the vehicle treated group. In two separate groups, infusions of neither
clevidipine nor
fenoldopam (5.0 nmol/kg(-1) min(-1)) for 60 min beginning 10 min before reperfusion, improved filtration fraction. However,
clevidipine treatment markedly improved tubular function in that loss of
sodium and water were significantly attenuated and UV and UNaV were restored towards basal levels. In contrast, in the
fenoldopam group, tubular function was further deteriorated as evidenced by exacerbated losses of
sodium and water. These observations suggest that whereas both
clevidipine and
fenoldopam were potent
natriuretic agents, only the
calcium antagonist was effective in preserving renal function in the present experimental model of ischemic
renal failure.