title: Effect of heme arginate administration on blood pressure in spontaneously hypertensive rats.
abstract: Cytochrome P450 content and activities are increased in the kidneys of spontaneously hypertensive rats (SHR) as compared with those of normotensive, Wistar-Kyoto (WKY), control rats during the period of rapid elevation of blood pressure. We studied the effect of heme arginate, a potent inducer of heme oxygenase (EC 1.14.99.3), on microsomal cytochrome P450 levels and activities and blood pressure in SHR at 7 wk of age. Administration of heme arginate (15 mg/kg body weight for 4 d) resulted in a marked decrease in blood pressure from 156.3 +/- 4.7 to 129.8 +/- 4.5 mm Hg (P less than 0.001), whereas blood pressure in SHR receiving the vehicle control was not affected. The blood pressure of age-matched WKY was not affected by heme arginate. Heme oxygenase activity increased in both hepatic and renal microsomes of SHR and WKY by two- to four-fold after treatment with heme arginate. Maximal increase of heme oxygenase mRNA occurred 5-7 h after the last injection of heme arginate and returned to control levels after 24 h. The increase in heme oxygenase activity was associated with a parallel decrease in cytochrome P450 content and in the activity of cytochrome P450 omega/omega-1 arachidonate hydroxylases in kidneys of SHR. It is postulated that heme arginate treatment resulted in induction of heme oxygenase which consequently led to a diminution of cytochrome P450, especially the arachidonate omega/omega-1 hydroxylases leading to a marked decrease in 19-hydroxyeicosatetraenoic acid (HETE) and 20-HETE. The effect of heme arginate on blood pressure may be mediated via these biochemical events inasmuch as both 19-HETE and 20-HETE produced by the kidney may promote hypertension by causing vasoconstriction and sodium retention.
authors.affiliation: Department of Medicine, New York Medical College, Valhalla 10595.
authors.forename: R D
authors.initials: RD
authors.lastname: Levere
authors.forename: P
authors.initials: P
authors.lastname: Martasek
authors.forename: B
authors.initials: B
authors.lastname: Escalante
authors.forename: M L
authors.initials: ML
authors.lastname: Schwartzman
authors.forename: N G
authors.initials: NG
authors.lastname: Abraham
mesh_terms: D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D015152:Blotting, Northern; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006418:Heme / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY
chemical_list: D001095:Arachidonic Acids; D012333:RNA, Messenger; D016718:Arachidonic Acid; D006418:Heme; D006427:Hemin; D003577:Cytochrome P-450 Enzyme System; D001120:Arginine; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing); C048849:heme arginate