title: Mechanisms underlying the antihypertensive effect of Alstonia scholaris.
abstract: BACKGROUND
  Alstonia scholaris has a long history of use in the Ayurveda traditional treatment of various ailments including hypertension. We have reported the blood pressure lowering activity of the extract of A. scholaris. The following research aim to delineate the pharmacological mechanism involve in the antihypertensive action.
  
  
  METHODS
  Vasorelaxant effect of the n-butanol fraction of A. scholaris (NBF-ASME) was evaluated on rat aorta pre-contracted with phenyelphrine (PE, 1 µM). Aortic rings preparation were pre-incubated with various antagonists like 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ 10 μM), methylene blue (MB 10 μM), Nω-nitro-L-arginine methyl ester hydrochloride (l-NAME 10 μM), atropine (10 μM), indomethacin (1 μM), ML-9 and various K(+) channel blockers such as glibenclamide (10 μM) and tetraethyl ammonium (TEA 10 μM) for mechanism study.
  
  
  RESULTS
  The results showed that pre-incubation of aortic rings with the extract (0.5, 1 and 2mg/mL) significantly inhibit the contractile response of the rings to phenylephrine-induced contraction (p<0.05-0.001). Removal of endothelium, incubation with L-NAME, indomethacin, atropine and propranolol did not significantly affect the relaxation effect of NBF-ASME. Furthermore, the K(+) channel blockers, TEA and glibenclamide showed no inhibitory effect. However, aortic rings pretreated with ODQ and ML-9 showed a significant suppression of the relaxation curve of NBF-ASME (p<0.01-0.001). In Ca(2+)-free solution, NBF-ASME inhibits the release of intracellular Ca(2+) from the sarcoplasmic reticulum. NBF-ASME also inhibits calcium chloride (CaCl2)-induced contraction in endothelium-denuded aortic rings.
  
  
  CONCLUSIONS
  The results from this study suggests that A. scholaris exerts vasodilation via calcium channels blockade, direct activation of soluble guanylate cyclase and possibly by also inhibiting the formation of inositol 1, 4, 5-triphosphate.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM), 11800 Pulau Pinang, Malaysia.
authors.forename: Idris
authors.initials: I
authors.lastname: Bello
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM), 11800 Pulau Pinang, Malaysia.
authors.forename: Nasiba Salisu
authors.initials: NS
authors.lastname: Usman
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, University Sains Malaysia (USM), 11800 Pulau Pinang, Malaysia.
authors.forename: Roziahanim
authors.initials: R
authors.lastname: Mahmud
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM), 11800 Pulau Pinang, Malaysia. Electronic address: amzaini@usm.my.
authors.forename: Mohd Zaini
authors.initials: MZ
authors.lastname: Asmawi
mesh_terms: D020001:1-Butanol / Q000737:chemistry; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D031051:Alstonia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D012997:Solvents / Q000737:chemistry; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D018727:Muscarinic Antagonists; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D018160:Receptors, Cytoplasmic and Nuclear; D012997:Solvents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D015544:Inositol 1,4,5-Trisphosphate; D020001:1-Butanol; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP
keywords: Alstonia scholaris; Aorta rings; Hypertension; Mechanisms; Vasorelaxation