Heme oxygenase substrates acutely lower blood pressure in hypertensive rats. Johnson, Robert A., Manuel Lavesa, Katie Deseyn, Matthew J. Scholer, and Alberto Nasjletti. Department of Pharmacology, New York Medical College, Valhalla, New York 10595
APStracts 3:0089H, 1996.
Heme oxygenase catalyzes the metabolism of heme to biliverdin, free iron and carbon monoxide. The current study was designed to determine if treatment with the heme oxygenase substrates heme-L-arginate or heme-L-lysinate, to stimulate formation of heme oxygenase products, can lower blood pressure in the rat. Heme-L-arginate (45[mu]mol/kg; IP) and heme-L-lysinate (45[mu]mol/kg; IP) acutely lowered blood pressure in awake SHR by approximately 35?mmHg. For both heme oxygenase substrates, this effect was blunted by pretreatment with an inhibitor of heme oxygenase, zinc deuteroporphyrin 2,4-bis glycol. Heme-L-lysinate also lowered arterial pressure in DOCA-salt hypertensive rats and in rats with phenylephrine-induced hypertension, indicating that the vasodepressive actions of heme may be extended to other hypertensive models. However, neither heme-L -arginate nor heme-L-lysinate decreased the blood pressures in normotensive controls. The heme oxygenase product biliverdin did not lower blood pressure in SHR and the vasodepressive actions of heme-L -lysinate were unaffected by pretreatment with deferoxamine to chelate free iron. Carbon monoxide (12ml/kg,IP) lowered blood pressure in SHR and in rats made hypertensive by phenylephrine infusion, had no effect on blood pressure in WKY rats, and elicited only a modest vasodepressive response in normotensive Sprague-Dawley rats. We conclude that heme-bearing preparations can lower blood pressure in hypertensive rats, presumably via heme oxygenase-mediated formation of carbon monoxide. 

Received 11 August 1995; accepted in final form 22 February 1996.
APS Manuscript Number H757-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96