Renin release by diuretics
Nascimento, L.; Ayala, J.M.; Baquero, R.A.; Martinez-Maldonado, M.
Journal of Pharmacology and Experimental Therapeutics 208(3): 522-526
1979
ISSN/ISBN: 0022-3565 PMID: 430369 Document Number: 151016
The effects of ethacrynic acid (EA) on renin secretion were studied in anesthetized dogs during control conditions, bilateral ureteral obstruction (BUO) and upon release. EA elicited an increase in renin release in a dose ranging between 0.5-5 mg/kg during experimental conditions where a decrease in extracellular volume was prevented by judicious replacement of fluid loss. More important, EA elicited an increase in renin secretion under conditions of extreme extracellular volume expansion (10% b wt). Volume expansion with 0.9% saline increases Na excretion (UNaV) from control values of 90.9 .+-. 22.82 to 562.5 .+-. 122.50 .mu.eq/min (P < .001), fractional excretion of Na (CNa/GFR .times. 100) from 1.6 .+-. 0.40 to 10.1 .+-. 0.92% (P < .001) while significant drops in hematocrit (41.0 .+-. 3.44 .fwdarw. 29.0 .+-. 3.93, P < .001) and plasma renin activity (PRA, 10.7 .+-. 3.27 .fwdarw. 5.0 .+-. 1.76 ng/ml per h, P. < .001) were observed. Superimposition of EA on volume expansion resulted in a further increase in UNaV and CNa/GFR .times. 100, no change in hematocrit and a marked rise in PRA (5.0 .+-. 1.76 .fwdarw. 31.7 .+-. 4.59 ng/ml per h, P < .001). Administration of EA (5 mg/kg b wt.) elicited a significant natriuresis and PRA levels were 8.2 .+-. 2.74 ng/ml per h at control; 30.5 .+-. 6.08 (P < .02), 34.7 .+-. 5.55 (P < .001) and 28.6 .+-. 5.88 ng/ml per h (P < .05) at 30, 60 and 90 min, respectively. At its lowest dose, EA and metolazone elicited similar natriuresis; an increase in renin secretion was observed with the former and not with the latter. Renin release always rose with BUO and did not change further with EA. Upon release of BUO, renin fell in the control but did not change further with EA. Upon release of BUO renin fell in the control but not in the EA group. EA enhances renin release regardless of the state of extracellular volume; this does not depend on UNa; EA does not act in the absence of normal filtration. NaCl delivery to the distal nephron appears to be the primary regulator of renin release in the BUO model. EA, by blocking transport at the macula densa, simulates diminished delivery. Metolazone probably acts beyond the macula densa, thus, the failure to affect renin.