Cardiovascular and renal actions of endothelin: effects of calcium-channel blockers.
We have evaluated the effects of two calcium-channel blockers, verapamil (VP) and manganese (Mn), on endothelin (EN)-induced changes in systemic and renal function in pentobarbital sodium-anesthetized female rats and male and female dogs. In the rat studies, saline was infused at 24 microliters/min iv with or without (n = 10) two doses of VP (0.02 mg.kg-1.min-1, n = 5; 0.03 mg.kg-1.min-1, n = 3) or Mn (0.5 mg.kg-1.min-1, n = 5) throughout the entire experiment. After surgery, rats were allowed 60 min to stabilize, and three 20-min control clearances were collected. EN (100 ng.kg-1.min-1) was then added to the infusate for 30 min. EN alone caused an increase in mean arterial pressure (MAP) and a decrease in the glomerular filtration rate (GFR). VP at either dose and Mn totally blocked the EN-induced increase in MAP. However, the two calcium-channel blockers had no effect on the renal action of EN; the GFR (in ml/min) decreased (at 30 min of EN infusion) from 2.7 +/- 0.1 (SE) to 0.7 +/- 0.1 (P less than 0.01) in controls, from 2.5 +/- 0.3 to 0.4 +/- 0.3 with the lower dose of VP (P less than 0.01), from 2.3 +/- 0.1 to 0.6 +/- 0.2 with the higher dose of VP (P less than 0.01), and from 1.5 +/- 0.5 to 0.9 +/- 0.6 with Mn (P less than 0.05). Infusion of EN alone (10 ng.kg-1.min-1, n = 5) and EN with VP (50 micrograms/min, n = 3) into the renal artery of dogs reduced renal blood flow from 3.5 +/- 0.4 to 0.9 +/- 0.2 and from 3.6 +/- 0.6 to 1.2 +/- 0.6 ml.g-1.min-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Physiology and Biophysics, University of Cincinnati College of Medicine, Ohio 45267-0576.
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D016232:Endothelins; D004730:Endothelium, Vascular; D005260:Female; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008345:Manganese / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D016232:Endothelins; D010455:Peptides; D008345:Manganese; D014700:Verapamil