title: Indapamide potentiates the endothelium-dependent production of cyclic guanosine monophosphate by bradykinin in the canine femoral artery.
abstract: Indapamide is a sulfonamide diuretic agent that has antihypertensive properties. In the canine femoral artery, indomethacin reduces the endothelium-dependent relaxation induced by bradykinin, and indapamide restores the response. The aim of this study was to determine whether indapamide affects the release or the effects of endothelium-derived nitric oxide and prostanoids. The effect of indapamide on the production of endothelium-derived nitric oxide and prostacyclin was assessed indirectly by the measurement of the tissue content of cyclic guanosine monophosphate (GMP) and the accumulation of 6-keto-prostaglandin F1 alpha in the incubation medium, respectively. Indapamide did not affect the basal production of either cyclic GMP, cyclic adenosine monophosphate (AMP), or 6-keto-prostaglandin F1 alpha in the presence or absence of indomethacin. Indomethacin decreased the production of cyclic AMP and the release of 6-keto-prostaglandin F1 alpha induced by bradykinin, and this was unaffected by indapamide. Indapamide enhanced the bradykinin-stimulated production of cyclic GMP in the presence of indomethacin and did not affect that evoked by 3 morpholino-sydnonimine, an exogenous donor of nitric oxide. Indomethacin had no significant effect on the production of cyclic GMP stimulated by either bradykinin or 3 morpholino-sydnonimine. These studies demonstrate that the potentiation by indapamide of the relaxation evoked by bradykinin is associated with an enhanced production of cyclic GMP in the presence of indomethacin, which suggests that the production of endothelium-derived nitric oxide is increased.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
authors.forename: D C
authors.initials: DC
authors.lastname: Junquero
authors.forename: V B
authors.initials: VB
authors.lastname: Schini
authors.forename: P M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D006152:Cyclic GMP / Q000096:biosynthesis*; D004285:Dogs; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007190:Indapamide / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D011464:Epoprostenol; D007190:Indapamide; D006152:Cyclic GMP; D001920:Bradykinin; D007213:Indomethacin