title: Paradoxical augmentation of bradykinin-induced vasodilatation by xanthine/xanthine oxidase-derived free radicals in isolated guinea pig heart.
abstract: Increased generation of reactive oxygen species contribute to endothelial dysfunction in atherosclerosis, hypertension and heart failure. Recently, it was suggested that bursts of superoxide anions may inactivate endothelial surface-bound enzymes such as angiotensin converting enzyme (ACE). Here, we tested effects of xanthine/xanthine oxidase-derived superoxide anions on vascular responses and ACE activity in the isolated guinea pig heart. We analysed effects of intracoronary infusion of low concentration of xanthine oxidase (10 mU/ml) in the presence of xanthine (0,5 mM) (X/XO) on bradykinin, other endothelium-dependent and independent vasodilators (acetylcholine, ADP, SNAP), as well as vasoconstrictor responses to angiotensin I and angiotensin II. Surprisingly, X/XO significantly augmented coronary response to bradykinin without an effect on responses to ADP, acetylcholine, SNAP, angiotensin I and angiotensin II. In contrast, inhibition of ACE by perindoprilate (100 nM) resulted in augmentation of bradykinin-induced vasodilatation as well as diminution of angiotensin I-evoked vasoconstriction without an influence on other responses. In summary, in the isolated guinea pig heart, X/XO-derived free radicals selectively augmented coronary vasodilator response to bradykinin, which cannot be explained by X/XO-induced derangement of ACE. The mechanism of this paradoxical phenomenon, which might represent a defensive response of the coronary circulation to oxidative stress requires further investigations.
authors.affiliation: Department of Pharmacology, Jagiellonian University School of Medicine, Krakow, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Olszanecki
authors.forename: V I
authors.initials: VI
authors.lastname: Kozlovski
authors.forename: S
authors.initials: S
authors.lastname: Chłopicki
authors.forename: R J
authors.initials: RJ
authors.lastname: Gryglewski
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D005260:Female; D005609:Free Radicals / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D019820:Xanthine / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000494:pharmacology*
chemical_list: D005609:Free Radicals; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D019820:Xanthine; D000803:Angiotensin I; D014969:Xanthine Oxidase; D001920:Bradykinin