Macula densa derived nitric oxide in regulation of glomerular capillary pressure

Nitric oxide (NO) is produced by enzymes called nitric oxide synthases (NOS). At least three different isoforms of NOS have been identified in the kidney. This study examines the effects of selective inhibition of the inducible isoform (iNOS) and the neuronal isoform (bNOS) on the glomerular capillary pressure (P-GC), through studies of the tubuloglomerular feedback (TGF) mechanism in anaesthetized rats. The proximal tubular stop-flow pressure (P-SF) was measured to estimate changes in P-GC obtained after activation of the TGF system by varying the loop of Henle perfusion rate with artificial ultrafiltrate including vehicle, NOS inhibition or L-arginine. Infusion of nonspecific NOS inhibition (N-omega-Nitro-L-arginine) increased maximal TGF responses (Delta P-SF) by 84% and L-arginine decreased Delta P-SF by 37%. Aminoguanidine, a selective iNOS-inhibitor, failed to increase Delta P-SF, whereas the nonspecific NOS inhibitor methylguanidine increased Delta P-SF, by 64%. 7-Nitro indazole (7-NI), a selective bNOS inhibitor, increased Delta P-SF by 57% when infused intratubularly, and intraperitoneal administration of 7-NI increased Delta P-SF by 78%, without any change in blood pressure. Since bNOS is exclusively located in the macula densa (MD) cells, these results confirm and strengthen the obligatory role of MD-produced NO in regulation of TGF and P-GC, which has been suggested earlier. iNOS, widely expressed in the kidney, does not seem to play any important role in regulation of P-GC.