title: The presence of the endothelial layer reduces nitric oxide-induced hyporesponsiveness to phenylephrine in rat aorta.
abstract: A single exposure to nitric oxide (NO) donors produces a long-lasting hyporesponsiveness to phenylephrine (HRP) in rat aorta rings. Here the authors investigate the role of the endothelial layer in the development of NO-induced HRP and the putative role of endothelium-derived vasoconstrictors in counteracting it. The NO donor S-nitrosoacetyl-D,L-penicillamine (SNAP) induced a dose-dependent reduction in the maximal effect (Emax) of phenylephrine. In rings without endothelium, Emax dropped to 60%, 25%, and 10% of control values 1 h after a 30-min incubation with SNAP (2, 20, and 200 microM, respectively). In contrast, the presence of endothelium prevented the HRP induced by 2 microM SNAP and significantly reduced the HRP elicited by 20 and 200 microM SNAP (Emax reductions of 50% and 65%, respectively), thereby characterizing the endothelium protective effect. Superoxide dismutase (SOD; 100 IU/mL), MnTBAP (a nonenzymatic SOD mimetic; 100 microM), captopril (10 microM), MK886 (a lipoxygenase inhibitor; 10 microM) and BQ 123 (endothelin receptor A antagonist; 1 microM) did not change the endothelium protective effect. Therefore, increased release of vasoconstrictors that would counteract NO-induced loss in phenylephrine responses cannot account for the protective effect of endothelium. In contrast, oxidation of sulphydryls with DTNB prevented the onset of SNAP-induced HRP. A better understanding of mechanisms by which the endothelial layer (or protein sulphydryl groups present in it) exerts its protective effect towards the NO-induced loss in physiological vasoconstriction is likely to be of value in cardiovascular conditions such as ischemia/reperfusion and septic shock.
authors.affiliation: Department of Pharmacology, Universidade Federal de Santa Catarina, SC, Brazil.
authors.forename: Márcia
authors.initials: M
authors.lastname: Terluk
authors.forename: Emiliana
authors.initials: E
authors.lastname: Cunha Da Silva
authors.forename: Tayze
authors.initials: T
authors.lastname: Antunes
authors.forename: Jamil
authors.initials: J
authors.lastname: Assreuy
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004351:Drug Resistance / Q000187:drug effects / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D009924:Organ Culture Techniques; D010656:Phenylephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D012772:Shock, Septic / Q000188:drug therapy / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D013438:Sulfhydryl Compounds; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D004228:Dithionitrobenzoic Acid; D013482:Superoxide Dismutase