Selective neuronal nitric oxide synthase inhibition blocks furosemide-stimulated renin secretion in vivo. Beierwaltes, William H. Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202
APStracts 2:0068F, 1995.
The macula densa is a regulatory site for renin. It contains exclusively the neuronal isoform of nitric oxide synthase (NOS), suggesting nitric oxide (NO) could stimulate renin secretion through the macula densa pathway. To test whether neuronal NOS mediates renin secretion, renin was stimulated by either the renal baroreceptor or the diuretic furosemide (acting through the macula densa pathway). Renin secretion rate (RSR) was measured in 12 inactin-anesthetized rats at normal (104 +/-3 mmHg) and reduced renal perfusion pressure (65 +/-1 mmHg), before and after selective blockade of the neuronal NOS with 7-nitro indazole (7-NI, 50 mg/kg, I.P.). 7-NI had no effect on basal blood pressure (BP)(102 +/-2 mmHg) or renal blood flow (RBF). Decreasing renal perfusion pressure doubled RSR from 11.8 +/ -3.3 to 22.9 +/-5.7 ngAI/hr/min (p<0.01). Similarly, in 7-NI-treated rats, reduced perfusion doubled RSR from 8.5 +/-1.8 to 20.5 +/-6.2 ngAI/hr/min (p<0.01). Renal hemodynamics and RSR were measured in response to 5 mg/kg I.V. furosemide in 12 control rats and 11 rats treated with 7-NI. Blocking neuronal NOS did not alter blood pressure (102 +/-2 mmHg), RBF (5.8 +/-0.4 ml/min/gkw) or renal vascular resistance (18.7 +/-1.4 mmHg/ml/min/gkw). In control rats, furosemide doubled RSR (from 6.5 +/-3.0 to 13.1 +/-3.6 ng AI/hr/min; p<0.005). In contrast, 7-NI treatment completely blocked furosemide-stimulated RSR (from 8.9 +/-2.9 to 7.0 +/-2.3 ng AI/hr/min). Thus selective inhibition of neuronal NOS completely abolished furosemide-stimulated renin secretion. These results suggest that NO synthesized in the macula densa is an important intermediary in renin stimulation through the macula densa pathway. 

Received 3 March 1995; accepted in final form 25 April 1995.
APS Manuscript Number F73-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  2 May 1995.