title: Role of heme oxygenase in modulating endothelial function in mesenteric small resistance arteries of spontaneously hypertensive rats.
abstract: It has been proposed that endothelial dysfunction is due to the excessive degradation of nitric oxide (NO) by oxidative stress. The enzyme heme-oxygenase (HO) seems to exert a protective effect on oxidative stress in the vasculature, both in animal models and in humans. The objective of this study is to evaluate the effects of inhibition or activation of HO on endothelial function in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). Six SHR were treated with cobalt protoporphyrin IX 50 mg/Kg (CoPP), an activator of HO; six SHR with stannous mesoporphyrin 30 mg/Kg (SnMP), an inhibitor of HO, and six SHR with saline. As controls, six Wistar-Kyoto rats (WKY) were treated with CoPP, six WKY with SnMP, and six WKY with saline. Drugs were injected in the peritoneum once a week for 2 weeks. Systolic blood pressure (SBP) was measured (tail cuff method) before and after treatment. Mesenteric small resistance arteries were mounted on a micromyograph. Endothelial function was evaluated as a cumulative concentration-response curve to acetylcholine (ACH), before and after preincubation with N(G)-methyl-L-arginine (L-NMMA, inhibitor of NO synthase), and to bradykinin (BK). In SHR treatment with CoPP, improved ACH-and BK-induced vasodilatation (ANOVA p < 0.001) and this improvement was abolished by L-NMMA (ANOVA p < 0.001). SnMP was devoid of effects on endothelial function. In WKY, both activation and inhibition of HO did not substantially affect endothelium-mediated vasodilatation. The stimulation of HO seems to induce an improvement of endothelial dysfunction in SHR by possibly reducing oxidative stress and increasing NO availability.
authors.affiliation: Clinica Medica, Department of Medical and Surgical Sciences, University of Brescia, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Porteri
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Rodella
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
authors.forename: Damiano
authors.initials: D
authors.lastname: Rizzoni
authors.forename: Silvia
authors.initials: S
authors.lastname: Paiardi
authors.forename: Carolina
authors.initials: C
authors.lastname: de Ciuceis
authors.forename: Gianluca E M
authors.initials: GE
authors.lastname: Boari
authors.forename: Eleonora
authors.initials: E
authors.lastname: Foglio
authors.forename: Gaia
authors.initials: G
authors.lastname: Favero
authors.forename: Nicola
authors.initials: N
authors.lastname: Rizzardi
authors.forename: Caterina
authors.initials: C
authors.lastname: Platto
authors.forename: Enrico
authors.initials: E
authors.lastname: Agabiti Rosei
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000502:physiology*; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology*; D008665:Metalloporphyrins / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011524:Protoporphyrins; C518404:stannous mesoporphyrin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C007095:cobaltiprotoporphyrin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D000109:Acetylcholine; D001920:Bradykinin