1: Am J Hypertens. 2002 Dec;15(12):1074-80. 

Vascular effects of a heme oxygenase inhibitor are enhanced in the absence of
nitric oxide.

Johnson FK, Teran FJ, Prieto-Carrasquero M, Johnson RA.

Department of Physiology, Tulane University Health Sciences Center, New Orleans,
Louisiana 70112, USA. fruzsi23@aol.com

BACKGROUND: Vascular endothelium and smooth muscle express heme oxygenase (HO)
that metabolizes heme to biliverdin, iron and carbon monoxide (CO). Carbon
monoxide promotes endothelium-independent vasodilation, but also inhibits nitric
oxide formation. This study examines the hypothesis that an inhibitor of HO
promotes endothelium-independent vasoconstriction, which is attenuated in the
presence of unabated nitric oxide formation. METHODS: In vivo studies were
conducted in anesthetized male Sprague-Dawley (SD) rats instrumented with flow
probes and arterial catheters. In vitro experiments were performed on
pressurized first-order gracilis muscle arterioles isolated from male SD rats
superfused with oxygenated modified Krebs buffer. RESULTS: Vascular smooth
muscle and endothelium showed positive HO-1 and HO-2 immunostaining. In
anesthetized rats the HO inhibitor chromium mesoporphyrin (CrMP; 45 micromol/kg
intraperitoneally) had minimal effect on hindlimb resistance. However, in
animals pretreated with N(omega)-nitro-L-arginine methyl ester (L-NAME; 300
mg/kg intraperitoneally), CrMP substantially increased hindlimb resistance. In
contrast, in rats infused with phenylephrine to increase blood pressure and
vascular tone, CrMP had no effect on hindlimb resistance. In isolated arterioles
denuded of endothelium, CrMP (15 micromol/L) caused a powerful vasoconstriction,
which was abolished in the presence of a functional endothelium. In arterioles
with intact endothelium pretreated with L-NAME (1 mmol/L), or with L-NAME and
sodium nitroprusside (10 to 30 nmol/L), CrMP promoted a similarly powerful
vasoconstriction as in vessels denuded of endothelium. CONCLUSIONS: These
results suggest that smooth muscle-derived CO may contribute to
endothelium-independent regulation of vascular tone by providing a vasodilatory
influence. Furthermore, the dilatory effects of endogenous CO are offset by a
unique interaction between the CO and nitric oxide systems.

PMID: 12460703 [PubMed - indexed for MEDLINE]