Macula densa derived nitric oxide in regulation of glomerular capillary pressure

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 ω -Nitro-L-arginine) increased maximal TGF responses (ΔP SF ) by 84% and L-arginine decreased ΔP sf by 37%. Aminoguanidine, a selective iNOS-inhibitor, failed to increase ΔP SF , whereas the nonspecific NOS inhibitor methylguanidine increased ΔP SF by 64%. 7-Nitro indazole (7-NI), a selective bNOS inhibitor, increased ΔP SF by 57% when infused intratubularly, and intraperitoneal administration of 7-NI increased ΔP 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 .