Inhibition of intrarenal nitric oxide stimulates renin secretion
through a macula densa-mediated mechanism.
Schnackenberg, Christine G., Barbara L. Tabor, Mark H. Strong, Joey P.
Granger.
Department of Physiology and Biophysics, University of Mississippi
Medical Center
APStracts 3:0362R, 1996.
Because endothelial-derived factors are known to have multiple actions
throughout the body, the role of nitric oxide (NO) produced within
the kidney in the regulation of renin release is still unclear.
Therefore, the objectives of this study were to determine the effect
of local NO synthesis inhibition within the kidney on renin secretion
rate and to determine whether the macula densa mechanism mediates the
effect of NO on renin secretion rate in dogs. The NO synthesis
inhibitor NW-nitro-L-arginine-methyl ester (L-NAME) was administered
via the renal artery at 5 [mu]g/kg/min to dogs with normal kidney
function and to dogs with the macula densa mechanism blocked,
established by using the non-filtering kidney model. In dogs with
normal kidney function, renal artery pressure (RAP) and glomerular
filtration rate (GFR) remained constant throughout the experiment
(131 +/- 5 mmHg and 22.6 +/- 3.0 ml/min). However, intrarenal NO
synthesis inhibition decreased renal blood flow (RBF) by 16% (240 +/-
22 to 201 +/- 23 ml/min) and increased renal vascular resistance
(RVR) by 24% (0.59 +/- 0.08 to 0.73 +/- 0.09 mmHg/ml/min). In
addition, L-NAME decreased the fractional excretion of lithium by 27%
(30.0 +/- 3.7% to 21.6 +/- 4.3%) and decreased the fractional
excretion of sodium by 35% (0.86 +/- 0.29% to 0.56 +/- 0.21%).
Associated with these changes in renal function, renin secretion rate
increased by 194% and 235%. In marked contrast, renin secretion rate
remained constant in dogs with the macula densa mechanism blocked.
Intrarenal NO synthase blockade decreased RSR by 4% and 10% in dogs
with the macula densa mechanism blocked. The RAP, RBF, and RVR
responses to intrarenal NO synthesis inhibition in dogs with the
macula densa mechanism blocked were similar to the renal hemodynamic
response in dogs with normal kidney function. In summary, we have
demonstrated that intrarenal NO synthesis blockade enhances renin
secretion in dogs. The macula densa mechanism appears to play an
important role in mediating the effect of intrarenal NO synthesis
inhibition on renin release.
Received 4 October 1995; accepted in final form 11 September
1996.
APS Manuscript Number R627-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996