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 th e kidney in the regulation of renin release is still unclear. Therefor e, 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 eff ect of NO on renin secretion rate in dogs. The NO synthesis inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) was administered via th e renal artery at 5 mu g . kg(-1). min(-1) to dogs with normal kidney function and to dogs with the macula densa mechanism blocked, establis hed by using the nonfiltering kidney model. In dogs with normal kidney function, renal arterial pressure (RAP) and glomerular filtration rat e (GFR) remained constant throughout the experiment (131 +/- 5 mmHg an d 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 . ml(-1). min). In addition, L-NAM E decreased the fractional excretion of lithium by 27% (30.0 +/- 3.7 t o 21.6 +/- 4.3%) and decreased the fractional excretion of sodium by 3 5% (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 ma rked contrast, renin secretion rate remained constant in dogs with the macula densa mechanism blocked. Intrarenal NO synthase blockade decre ased 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 r enal hemodynamic response in dogs with normal kidney function. In summ ary, we have demonstrated that intrarenal NO synthesis blockade enhanc es 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.