title: Heme oxygenase-mediated endothelial dysfunction in DOCA-salt, but not in spontaneously hypertensive, rat arterioles.
abstract: Vascular heme oxygenase (HO) metabolizes heme to form carbon monoxide. Carbon monoxide inhibits nitric oxide synthase and promotes endothelium-dependent vasoconstriction. We reported HO-1-mediated endothelial dysfunction in Dahl salt-sensitive hypertension. Previous studies suggested that salt-sensitive hypertensive rats, but not spontaneously hypertensive rats (SHR), display endothelial dysfunction. This study examines the hypothesis that HO-1-mediated arteriolar endothelial dysfunction develops in deoxycorticosterone acetate (DOCA)-salt hypertensive (DOCA) rats, but not in SHR. Uninephrectomized (isoflurane anesthesia) male Sprague-Dawley rats received DOCA injections and saline drinking solution for 4 wk. Rats subjected to sham surgery received vehicle injections and tap water. Blood pressure was elevated in DOCA rats and SHR compared with sham and Wistar-Kyoto (WKY) groups. Aortic HO-1 expression and blood carboxyhemoglobin levels were elevated in the DOCA group, but not in SHR. In isolated gracilis muscle arterioles, ACh caused concentration-related vasodilation in all groups, with attenuated maximum responses in DOCA, but not in SHR, arterioles. Acute pretreatment with an inhibitor of HO, chromium mesoporphyrin, restored ACh-induced responses in DOCA arterioles to sham levels. ACh responses remained the same in SHR and WKY arterioles after chromium mesoporphyrin treatment. These data show that HO-1 levels and activity are increased and arteriolar responses to ACh are decreased in DOCA rats, but not in SHR. Furthermore, in DOCA arterioles, an inhibitor of HO restores ACh-induced vasodilation to sham levels. These results suggest that elevated HO-1 levels and activity, not resulting from hypertension per se, contribute to endothelial dysfunction in DOCA rats.
authors.affiliation: Tulane Hypertension and Renal Center of Excellence, Department of Physiology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA. Fruzsi123@aol.com
authors.forename: Fruzsina K
authors.initials: FK
authors.lastname: Johnson
authors.forename: William
authors.initials: W
authors.lastname: Durante
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Peyton
authors.forename: Robert A
authors.initials: RA
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001160:Arterioles / Q000503:physiopathology*; D001794:Blood Pressure; D002263:Carboxyhemoglobin / Q000378:metabolism; D003900:Desoxycorticosterone; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride
chemical_list: D003900:Desoxycorticosterone; D012965:Sodium Chloride; D002263:Carboxyhemoglobin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1