Effects of fenoldopam, a dopamine D-1 agonist, and clevidipine, a calcium channel antagonist, in acute renal failure in anesthetized rats.
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.
Stephens
Christopher T
CT
Institute for Cardiovascular Studies, College of Pharmacy, University of Houston, TX 77204, USA.
Jandhyala
Bhagavan S
BS
D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D018818:Fenoldopam / Q000494:pharmacology / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007511:Ischemia; D008297:Male; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012078:Renal Artery Obstruction / Q000150:complications; D012079:Renal Circulation / Q000187:drug effects*
D018491:Dopamine Agonists; D011725:Pyridines; C118563:clevidipine; D018818:Fenoldopam