BAY K 8644 inhibits renin secretion in isolated perfused rat kidneys.
There are only a few previous reports of the renal effects of the Ca channel agonist BAY K 8644, and the renin secretory effects in particular are unclear. In the present experiments, isolated rat kidneys were perfused at 120 and 100 mm Hg before and after adding BAY K 8644 to the perfusate (0.05 microM final concentration), and perfusate flow rate, glomerular filtration rate (GFR), urine flow, Na excretion, and renin secretory rate were measured. BAY K 8644 increased renal vascular resistance, as evidence by decreases in perfusate flow and GFR at constant perfusion pressure, and decreased urine flow and Na excretion. Renin secretory rates were 51 +/- 4 versus 23 +/- 3 ng A I hr-1 min-1 at 120 mm Hg (p < 0.01), and 184 +/- 54 versus 38 +/- 14 ng A I hr-1 min-1 at 100 mm Hg (p < 0.01), in the absence versus the presence of BAY K 8644, respectively. Therefore, BAY K 8644 inhibits renin secretion at constant perfusion pressure and blunts the stimulatory effect on renin secretion of decreases in renal perfusion pressure. Collectively, these observations add to the growing evidence that the renin secreting juxtaglomerular cells have voltage-operated Ca channels, that depolarization-induced Ca influx inhibits renin secretion, and that Ca is an inhibitory second messenger in the renin secretory process.
Jones-Dombi
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Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Churchill
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D015203:Reproducibility of Results
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D012083:Renin