1: Hypertension. 1995 Feb;25(2):166-9. 

A heme oxygenase product, presumably carbon monoxide, mediates a vasodepressor
function in rats.

Johnson RA, Lavesa M, Askari B, Abraham NG, Nasjletti A.

Department of Pharmacology, New York Medical College, Valhalla 10595.

Heme oxygenase is a mammalian enzyme that converts heme to biliverdin and carbon
monoxide. Carbon monoxide activates soluble guanylate cyclase and relaxes
vascular smooth muscle, and it has been implicated as a potential
neuromessenger. The regulatory functions of endogenous carbon monoxide on
hemodynamics are not known. Zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG)
inhibits heme oxygenase in rats and thus permits assessment of the hemodynamic
response to inhibition of endogenous carbon monoxide synthesis. In chronically
instrumented, awake male Sprague-Dawley rats, ZnDPBG (45 mumol/kg IP) increased
mean arterial pressure (19 +/- 2%, P < .05) and total peripheral resistance (47
+/- 4%, P < .05), decreased cardiac output (-16 +/- 2%, P < .05), but did not
affect heart rate. Another heme oxygenase inhibitor, zinc protoporphyrin IX (45
mumol/kg IP), also increased arterial pressure (17 +/- 5%, P < .05), with no
effect on heart rate. In contrast, neither the nonmetallic deuteroporphyrin
2,4-bis glycol (45 mumol/kg IP) nor bilverdin (45 mumol/kg IP) had any effect on
blood pressure or heart rate. These findings suggest that ZnDPBG and zinc
protoporphyrin IX increase arterial pressure by inhibiting heme oxygenase
activity. After pretreatment with chlorisondamine (5 mg/kg IP) or prazosin (5
mg/kg IP) to inhibit autonomic ganglionic or alpha 1-adrenoceptor functions,
respectively, ZnDPBG did not affect arterial pressure or heart rate. This
suggests that ZnDPBG-induced increases in blood pressure rely on autonomic
nervous function. We conclude that the pressor response to heme oxygenase
inhibitors results from withdrawal of the inhibitory influence of endogenous
carbon monoxide on a pressor mechanism mediated by the autonomic nervous system.

PMID: 7843765 [PubMed - indexed for MEDLINE]