Inhibition of intrarenal NO stimulates renin secretion through a macula densa-mediated mechanism.
Because endothelium-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 (RSR) and to determine whether the macula densa mechanism mediates the effect of NO on renin secretion rate in dogs. The NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) was administered via the renal artery at 5 microg x kg(-1) x min(-1) to dogs with normal kidney function and to dogs with the macula densa mechanism blocked, established by using the nonfiltering kidney model. In dogs with normal kidney function, renal arterial pressure (RAP) and glomerular filtration rate (GFR) remained constant throughout the experiment (131 +/- 5 mmHg and 22.6 +/- 3.0 ml/min, respectively). 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 x ml(-1) x 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.
Schnackenberg
C G
CG
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216, USA.
Tabor
B L
BL
Strong
M H
MH
Granger
J P
JP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005919:Glomerular Filtration Rate; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000502:physiology*; D008094:Lithium / Q000652:urine; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology*; D012083:Renin / Q000378:metabolism*; D012964:Sodium / Q000652:urine; D014655:Vascular Resistance
D009569:Nitric Oxide; D008094:Lithium; D012964:Sodium; D019001:Nitric Oxide Synthase; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester