title: Vasorelaxant and hypotensive effects of a hydroalcoholic extract from the fruits of Nitraria sibirica Pall. (Nitrariaceae).
abstract: BACKGROUND
  Fruits of Nitraria sibirica Pall. are traditionally used in Uighur medicine to treat hypertension. This study aimed to support that folk use by defining their vasoactive and hypotensive properties.
  
  
  METHODS
  The vasorelaxant activity and the underlying mechanisms of a hydroalcoholic extract from the fruits of Nitraria sibirica Pall. (NSHE) were evaluated on thoracic aortic rings isolated from Wistar rats. In addition, the acute hypotensive effect of NSHE was assessed in anesthetized spontaneously hypertensive rats (SHR) and in their normotensive control Wistar Kyoto (WKY) rats.
  
  
  RESULTS
  NSHE (0.1-10 g/l) was clearly more effective to induce vasodilation of phenylephrine- (PE, 1 μM) than high KCl- (60mM) pre-contracted aortic rings with respective E(max) values of 82.9±2.2% and 34.8±3.6%. The removal of endothelium almost abolished the relaxant effect of the extract. In addition, pre-treatment with N(w)-nitro-L-arginine-methyl ester (L-NAME, 100 μM), atropine (1 μM) or charybdotoxin (30 nM) plus apamin (30 nM), respective blockers of nitric oxide (NO) synthase, muscarinic receptors and endothelium-derived hyperpolarizing factor (EDHF), significantly reduced the observed effect of NSHE. By contrast, the cyclooxygenase (COX) inhibitor indomethacin (10 μM) or the K(+) channels blockers glibenclamide (10 μM), iberiotoxin (30 nM) and 4-amino-pyridine (4-AP, 1 mM) failed to modify the vasodilation. Finally, the acute intravenous injection of NSHE (1, 5, 10, 20 mg/kg) induced an immediate and transient hypotensive effect in anesthetized SHR and in WKY rats.
  
  
  CONCLUSIONS
  This experimental animal study suggests that hydroalcoholic extract from the fruits of Nitraria sibirica Pall. induces vasorelaxation through an endothelium-dependent pathway involving NO synthase (NOS) activation, EDHF production and muscarinic receptor stimulation. Additionally, our results determine that this vasorelaxant effect is translated by a significant hypotensive effect.
authors.affiliation: EA 4267 Sciences Séparatives, Biologiques et Pharmaceutiques, UFR des Sciences Médicales et Pharmaceutiques, 25030 Besançon, France.
authors.forename: François
authors.initials: F
authors.lastname: Senejoux
authors.forename: Corinne
authors.initials: C
authors.lastname: Girard
authors.forename: Haji Akber
authors.initials: HA
authors.lastname: Aisa
authors.forename: Mahinur
authors.initials: M
authors.lastname: Bakri
authors.forename: Parhat
authors.initials: P
authors.lastname: Kerram
authors.forename: Alain
authors.initials: A
authors.lastname: Berthelot
authors.forename: Françoise
authors.initials: F
authors.lastname: Bévalot
authors.forename: Céline
authors.initials: C
authors.lastname: Demougeot
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001685:Biological Factors / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004789:Enzyme Activation; D000431:Ethanol / Q000737:chemistry*; D005638:Fruit; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019684:Magnoliopsida / Q000737:chemistry; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D012997:Solvents / Q000737:chemistry*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D001685:Biological Factors; D010636:Phenols; D010936:Plant Extracts; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D012997:Solvents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D000431:Ethanol; D019001:Nitric Oxide Synthase