Heme oxygenase-1–derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo

R Motterlini, A Gonzales, R Foresti, JE Clark… - Circulation …, 1998 - Am Heart Assoc
R Motterlini, A Gonzales, R Foresti, JE Clark, CJ Green, RM Winslow
Circulation research, 1998Am Heart Assoc
The enzyme heme oxygenase, which exists in inducible (HO-1) and constitutive (HO-2)
isoforms, catalyzes the degradation of heme to biliverdin and CO in mammalian tissues. CO
has been implicated in the control of vascular tone in a manner similar to that for NO. In the
present study, we investigated the contribution of the heme oxygenase/CO pathway to the
modulation of acute hypertensive responses in vivo induced by (1) ααHb, a chemically
modified hemoglobin known to scavenge NO, and (2) N G-nitro-l-arginine methyl ester (L …
Abstract
—The enzyme heme oxygenase, which exists in inducible (HO-1) and constitutive (HO-2) isoforms, catalyzes the degradation of heme to biliverdin and CO in mammalian tissues. CO has been implicated in the control of vascular tone in a manner similar to that for NO. In the present study, we investigated the contribution of the heme oxygenase/CO pathway to the modulation of acute hypertensive responses in vivo induced by (1) ααHb, a chemically modified hemoglobin known to scavenge NO, and (2) NG-nitro-l-arginine methyl ester (L-NAME), a competitive NOS inhibitor. Experiments were carried out in conscious rats in which femoral arteries and veins were surgically catheterized 1 or 5 days before treatment with the vasoconstrictor agents. Intravenous infusion of ααHb (8% solution) or L-NAME (30 mmol/kg) produced an acute and significant increase in mean arterial pressure (P<0.05) in rats at 5 days after catheter implantation. In contrast, no change in blood pressure was observed when ααHb or L-NAME was infused 1 day after the surgical intervention. The suppression of the hypertensive response observed at 1 day after surgery correlated with a significant (P<0.05) HO-1 expression in aorta, heart, and liver as well as increased aortic CO production and cGMP levels. At 1 day after surgery, pretreatment of animals with the heme oxygenase inhibitor zinc protoporphyrin IX (50 μmol/kg IP) markedly decreased aortic CO and cGMP levels and completely restored the vasoconstrictor effects of both ααHb and L-NAME. These results provide evidence for a crucial role of the heme oxygenase/CO pathway in the regulation of blood pressure under stress conditions in vivo.
Am Heart Assoc