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.
Rodriguez
Francisca
F
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA. francisca_rodrigues@nymc.edu
Zhang
Fan
F
Dinocca
Sandra
S
Nasjletti
Alberto
A
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