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 (PGC), through studies of the tubuloglomerular feedback (TGF) mechanism in anaesthetized rats. The proximal tubular stop-flow pressure (PSF) was measured to estimate changes in PGC 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 PSF) by 84% and L-arginine decreased delta PSF by 37%. Aminoguanidine, a selective iNOS-inhibitor, failed to increase delta PSF, whereas the nonspecific NOS inhibitor methylguanidine increased delta PSF by 64%. 7-Nitro indazole (7-NI), a selective bNOS inhibitor, increased delta PSF by 57% when infused intratubularly, and intraperitoneal administration of 7-NI increased delta PSF 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 PGC, which has been suggested earlier. iNOS, widely expressed in the kidney, does not seem to play any important role in regulation of PGC.
Thorup
C
C
Department of Physiology, Lund University, Sweden.
Erik
A
A
Persson
G
G
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002200:Capillary Resistance / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000201:enzymology*; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000502:physiology; D008297:Male; D008760:Methylguanidine / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D019335:Nitroarginine; D009569:Nitric Oxide; D008760:Methylguanidine; D001120:Arginine; D019001:Nitric Oxide Synthase; C004479:pimagedine; C080122:7-nitroindazole