title: Indapamide treatment modifies the vascular reactivity of normotensive rat mesenteric arteries ex vivo.
abstract: Indapamide is an antihypertensive diuretic drug of which the precise antihypertensive mechanism has not been clarified. The aim of the present study was to investigate with mesenteric arteries of normotensive rats the possible change in vascular reactivity ex vivo and in vitro after indapamide application, taking into special consideration the role of endothelium. After seven days of drug treatment in vivo with low-dose 0.3 mg/kg/day or high-dose 3 mg/kg/day of indapamide the effect on the vascular responses ex vivo were compared to controls. The contractions induced by noradrenaline (NA) or potassium chloride (KCl) were increased in vascular rings without endothelium in the high-dose indapamide group. No alterations in endothelium-dependent relaxation responses to acetylcholine (ACh) or endothelium-independent responses to sodium nitroprusside (SNP) were found between any of the treatment groups in vascular rings with or without endothelium. When indapamide (1 microM or 10 microM) was added in vitro for 10 min preincubation it did not significantly change the vascular contractions induced by cumulatively increased concentrations of NA or KCl. The relaxation responses induced by ACh or SNP were also not affected by indapamide pretreatment. Our results suggest that the lack of change in contractile response in vitro after indapamide pretreatment might be related to the prodrug nature of indapamide, which is not metabolized during the short preincubation.
authors.affiliation: Department of Pharmacology and Toxicology, University of Helsinki, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Tarkkila
authors.forename: I
authors.initials: I
authors.lastname: Paakkari
authors.forename: E
authors.initials: E
authors.lastname: Mervaala
authors.forename: R
authors.initials: R
authors.lastname: Nevala
authors.forename: H
authors.initials: H
authors.lastname: Vapaatalo
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D005665:Furosemide / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D066298:In Vitro Techniques; D007190:Indapamide / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D006852:Hydrochlorothiazide; D005665:Furosemide; D007190:Indapamide