Nitric oxide synthesis influences the renal vascular response to heme oxygenase inhibition.
We studied the effects of the heme oxygenase (HO) inhibitor stannous mesoporphyrin (SnMP; 40 micromol/kg i.v.) on renal hemodynamics in anesthetized rats with and without 48-h pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis. SnMP decreased renal blood flow (RBF) and increased renal vascular resistance (RVR) in both groups. The SnMP-induced reduction of RBF in L-NAME-pretreated rats was more prominent than in rats without pretreatment (43 +/- 7 vs. 13 +/- 3%) as was the SnMP-induced elevation of RVR (87 +/- 31 vs. 14 +/- 5%). The renal vasoconstrictor effect of SnMP is linked, in part, to amplification of prevailing neurohormonal constrictor mechanisms, since in L-NAME-pretreated rats it was prevented by concurrent administration of prazosin or losartan. However, SnMP (15 micromol/l) also elicits vasoconstriction in isolated, pressurized renal interlobular arteries and the response is more intense in vessels obtained from L-NAME-pretreated rats than from rats without pretreatment. These data indicate that the status of NO synthesis conditions the vascular response to HO inhibition in the rat kidney.
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA. francisca_rodrigues@nymc.edu
Francisca
F
Rodriguez
Fan
F
Zhang
Sandra
S
Dinocca
Alberto
A
Nasjletti
D000818:Animals; D001664:Biliverdine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002248:Carbon Monoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008652:Mesoporphyrins / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000033:anatomy & histology / Q000187:drug effects*; D012079:Renal Circulation / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D008652:Mesoporphyrins; D009569:Nitric Oxide; C031468:mesoporphyrin IX; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D006419:Heme Oxygenase (Decyclizing); D001664:Biliverdine; D019331:NG-Nitroarginine Methyl Ester