Exogenous cGMP prevents decrease in diuresis and natriuresis induced by inhibition of NO synthesis.
We previously demonstrated that the intravenous infusion of the specific inhibitor of nitric oxide (NO) synthesis, NG-nitro-L-arginine methyl ester (L-NAME), over a period of 60 min elevates mean arterial pressure (MAP) and reduces renal hemodynamics and excretory function. The objective of the present study was to determine the ability of a guanosine 3',5'-cyclic monophosphate (cGMP) analogue, 8-bromo-cGMP (8-BrcGMP), in preventing the increase in MAP and the reductions in renal plasma flow (RPF), glomerular filtration rate (GFR), urine flow (UV), and sodium excretion rate (UNaV) induced by intravenous infusion of L-NAME in rats. As expected, the infusion of L-NAME (50 micrograms.kg-1.min-1) increased (P < 0.05) MAP and reduced (P < 0.05) RPF, GFR, UV, and UNaV. The administration of 8-BrcGMP (100 micrograms.kg-1.min-1) and L-NAME resulted in no change in MAP, RPF, and GFR. However, decreased (P < 0.05) UV and UNaV were still observed. When 8-BrcGMP (200 micrograms.kg-1.min-1) and L-NAME were infused together, no significant changes in MAP or in renal function were observed. To prove the specificity of the 8-BrcGMP preventive effects, dibutyryl cAMP (200 micrograms.kg-1.min-1) and L-NAME (50 micrograms.kg-1.min-1) were infused together. Under these conditions, MAP, RPF, GFR, UV, and UNaV were modified in a manner similar to that observed during the infusion of L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, Faculty of Medicine, Universidad Complutense, Madrid, Spain.
V
V
Lahera
J
J
Navarro
M L
ML
Biondi
L M
LM
Ruilope
J C
JC
Romero
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009318:Natriuresis / Q000187:drug effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects
C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester