HEME OXYGENASE SUBSTRATES ACUTELY LOWER BLOOD-PRESSURE IN HYPERTENSIVE RATS

Heme oxygenase catalyzes the metabolism of heme to biliverdine, free i ron, and carbon monoxide. The current study was designed to determine if treatment with the heme oxygenase substrates heme-L-arginate or hem e-L-lysinate, to stimulate formation of heme oxygenase products, can l ower 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 aw ake spontaneously hypertensive rats (SHR) by similar to 35 mmHg. For b oth heme oxygenase substrates, this effect was blunted by pretreatment with an inhibitor of heme oxygenase, zinc deuteroporphyrin 2,4-bis gl ycol. Heme-L-lysinate also lowered arterial pressure in deoxycorticost erone acetate-salt hypertensive rats and in rats with phenylephrine-in duced 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 blood pressure in normotensive controls. The heme oxygenase product biliverdine did not lower blood pressure in SHR, and the vasodepressive actions of heme-L-lysinate wer e unaffected by pretreatment with deferoxamine to chelate free iron. C arbon monoxide (12 ml/kg ip) lowered blood pressure in SHR and in rats made hypertensive by phenylephrine infusion, had no effect on blood p ressure in Wistar-Kyoto rats, and elicited only a modest vasodepressiv e response in normotensive Sprague-Dawley rats. We conclude that heme- bearing preparations can lower blood pressure in hypertensive rats, pr esumably via heme oxygenase-mediated formation of carbon monoxide.