Signal transduction pathways involved in kinin B(2) receptor-mediated vasodilation in the rat isolated perfused kidney

British Journal of Pharmacology
K BagatéM Barthelmebs

Abstract

The signal transduction pathways involved in kinin B(2) receptor-related vasodilation were investigated in rat isolated perfused kidneys. During prostaglandin F(2alpha) or KCl-induced constriction, the vasodilator response to a selective B(2) receptor agonist, Tyr(Me)(8)bradykinin (Tyr(Me)(8)BK), was assessed. Tyr(Me)(8)BK produced a concentration- and endothelium-dependent relaxation that was decreased by about 30 - 40% after inhibition of nitric oxide (NO) synthase by N(G)-nitro-L-arginine (L-NOARG) or of cyclo-oxygenase by indomethacin; a greater decrease (about 40 - 50%) was observed after concomitant inhibition of the two pathways. High extracellular K(+) diminished Tyr(Me)(8)BK-induced relaxation by about 75% suggesting a major contribution of endothelium-derived hyperpolarization. The residual response was almost completely suppressed by NO synthase and cyclo-oxygenase inhibition. The K(+) channel inhibitors, tetrabutylammonium (non-specific) and charybdotoxin (specific for Ca(2+)-activated K(+) channel), suppressed Tyr(Me)(8)BK-induced relaxation resistant to L-NOARG and indomethacin. Inhibition of cytochrome P450 (clotrimazole or 7-ethoxyresorufin) decreased the NO/prostanoids-independent relaxation to Tyr(Me)(8)BK by ...Continue Reading

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Citations

Oct 14, 2005·Kidney International·David A LongRichard J Johnson
Oct 22, 2008·Biochemical Pharmacology·Inga I KramarenkoMaria N Garnovskaya
Jul 1, 2008·Microvascular Research·Dirk UhlmannHelmut Witzigmann
Dec 13, 2006·Toxicon : Official Journal of the International Society on Toxinology·Marcus Davis Machado BragaHelena Serra Azul Monteiro
Jan 1, 2014·Current Opinion in Nephrology and Hypertension·Mykola MamenkoOleh Pochynyuk
Dec 16, 2011·American Journal of Physiology. Renal Physiology·Charlotte Mehlin SorensenMax Salomonsson
Jan 11, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Yoshiteru MorioIvan F McMurtry
Oct 22, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Sakuji ShigematsuRonald J Korthuis

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