title: Cedrelopsis grevei induced hypotension and improved endothelial vasodilatation through an increase of Cu/Zn SOD protein expression.
abstract: This study was designed to investigate the cardiovascular consequences of oral administration of Cedrelopsis grevei (CG) in normotensive rats. Experiments were designed to investigate hemodynamic parameters in vivo as well as the consequences of CG treatment on the vasoconstriction response to norepinephrine and the vasorelaxant response to ACh ex vivo in isolated aortas and small mesenteric arteries (SMA). Treatment of male Wistar rats with 80 mg/kg CG for 4 wk induced a progressive decrease in systolic blood pressure. In the aorta, CG did not significantly alter the response to norepinephrine despite the participation of extraendothelial nitric oxide (NO)-induced hyporeactivity. In the SMA, contraction to norepinephrine was not modified by CG treatment even though it enhanced the participation of endothelial NO. Endothelium-dependent relaxation to ACh was increased in both the aorta and SMA from CG-treated rats. In the aorta from CG-treated rats, the mechanism involved superoxide dismutase (SOD)- and catalase-sensitive free radical production. The latter was associated with enhanced expression of Cu/Zn SOD and endothelial NO synthase. These results suggest that oral administration of CG produces a decrease in blood pressure in normotensive rats. This hemodynamic effect was associated with enhanced endothelium-dependent relaxation and an induction of Cu/Zn SOD and endothelial NO synthase expressions in the vessel wall. They also show subtle mechanisms that compensate for the increased participation of NO to maintain unchanged agonist-induced contractility. These data provide a pharmacological basis for the empirical use of CG against cardiovascular diseases.
authors.affiliation: Pharmacologie et Physicochimie des Interactions Cellulaires et Moléculaires, Unité Mixte de Recherche, Centre National de la Recherche Scientifique 7034, Illkirch, France.
authors.forename: Hantamalala
authors.initials: H
authors.lastname: Ralay Ranaivo
authors.forename: Olivier
authors.initials: O
authors.lastname: Rakotoarison
authors.forename: Angela
authors.initials: A
authors.lastname: Tesse
authors.forename: Christa
authors.initials: C
authors.lastname: Schott
authors.forename: Adolphe
authors.initials: A
authors.lastname: Randriantsoa
authors.forename: Annelise
authors.initials: A
authors.lastname: Lobstein
authors.forename: Ramaroson
authors.initials: R
authors.lastname: Andriantsitohaina
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D010936:Plant Extracts; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin