Effect of 6-aminonicotinamide on renin release in isolated rat kidney: possible role for the pentose pathway.
To study the association between renal renin release and the pentose pathway, we perfused nonfiltering kidneys from Sprague-Dawley rats with Krebs-Ringer bicarbonate buffer containing 5 mM glucose and 14 g/100 ml bovine serum albumin in the presence or in the absence of 0.25 mM 6-aminonicotinamide (6AN), an inhibitor of glucose-6-phosphate dehydrogenase, the rate-limiting step of the pentose pathway. Eleven kidneys perfused in the absence of 6AN had a renin secretion rate of 7.4 +/- 2.2 ng ANG I X min-1 X ml-1. In six kidneys perfused in the presence of 6AN, renin release was depressed to 0.56 +/- 0.24 ng ANG I X min-1 X ml-1. The renal renin content for four control kidneys was 56 +/- 3.3 ng ANG I X mg-1 X h-1 while in four kidneys perfused with 6AN renal renin content was lower, 35 +/- 2.9 ng ANG I X mg-1 X h-1. In the presence of 5 mM lactate, the renin release of eight nonfiltering kidneys was 0.31 +/- 0.06 ng ANG I X min-1 X ml-1. The addition of 6AN did not further depress renin secretion in the presence of lactate. 6-Aminonicotinamide also completely blocked furosemide-stimulated renin release without having any effect on glomerular filtration rate or furosemide-induced natriuresis. However, 6AN did not inhibit stimulation of renin secretion by isoproterenol. We conclude that 6-aminonicotinamide interferes with renin release by nonfiltering kidneys and also inhibits furosemide-stimulated renin release but does not affect beta-adrenergic-stimulated renin secretion. Glucose but not lactate is important for maintaining augmented rates of renin secretion in nonfiltering kidneys. 6-Aminonicotinamide significantly reduced renal renin content in the presence of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
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D015120:6-Aminonicotinamide / Q000494:pharmacology*; D000818:Animals; D005665:Furosemide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives*; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*
D009536:Niacinamide; D015120:6-Aminonicotinamide; D005665:Furosemide; D005954:Glucosephosphate Dehydrogenase; D012083:Renin; D007545:Isoproterenol