Effect of carvedilol on renal hemodynamics and renal excretory function in spontaneously hypertensive rats.
The effects of the novel antihypertensive agent, carvedilol, on renal hemodynamics and excretory function have been investigated and compared with the effects of labetalol in conscious, spontaneously hypertensive rats. Sustained intravenous infusion of carvedilol or labetalol at a rate of 10 micrograms/kg/min resulted in a significant decrease in blood pressure which was equivalent in magnitude for both drugs. Carvedilol had no effect on renal hemodynamic parameters; glomerular filtration rate, renal blood flow, and filtration fraction were unchanged. In contrast, labetalol decreased the glomerular filtration rate by 13% (p less than 0.01) and the filtration fraction was reduced from 28 to 24%. Inasmuch as renal blood flow was unchanged and perfusion pressure was reduced, both compounds decreased renal vascular resistance. Urine flow decreased and osmolality increased with both carvedilol and labetalol. However, excretion of electrolytes was affected differently with the two compounds. While sodium and potassium excretion were significantly decreased with labetalol, sodium and potassium excretion remained stable during carvedilol infusion, which represents an important beneficial effect for a potent systemic vasodilator. We conclude, therefore, that carvedilol does not compromise the renal autoregulatory integrity in hypertensive rats, and that the antihypertensive activity of the compound is associated with an apparent 'renal sparing' effect, in that the decrease in blood pressure does not compromise the urinary excretion of sodium.
Gellai
M
M
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa.
DeWolf
R
R
Ruffolo
R R
RR
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007741:Labetalol / Q000494:pharmacology; D008297:Male; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000187:drug effects; D010130:p-Aminohippuric Acid / Q000652:urine
D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D007741:Labetalol; D010130:p-Aminohippuric Acid