title: Modulation of vascular reactivity in normal, hypertensive and diabetic rat aortae by a non-antioxidant flavonoid.
abstract: In this study, we report the effects of a non-antioxidant flavonoid flavone on vascular reactivity in Wistar-Kyoto (WKY) rat isolated aortae. Whether flavone directly modulates vascular reactivity in spontaneously hypertensive rat (SHR) and streptozotocin-induced diabetic-WKY rat isolated aortae was also determined. Thoracic aortic rings were mounted in organ chambers and exposed to various drug treatments in the presence of flavone (10 microM) or its vehicle (DMSO), which served as control. Pretreatment with flavone enhanced relaxant effects to endothelium-dependent vasodilator acetylcholine (ACh) and attenuated contractile effects to alpha(1)-receptor agonist phenylephrine (PE) in WKY aortae compared to those observed in control aortic rings. Flavone had no effect on relaxations to ACh in WKY aortae incubated with either L-NAME or methylene blue, but enhanced relaxations to ACh in WKY aortae incubated with indomethacin or partially depolarized with KCl. Relaxations to ACh are totally abolished in both control or flavone pretreated endothelium-denuded WKY aortae. Flavone attenuated the inhibition by beta-NADH of ACh-induced relaxation in WKY aortae, but it had no significant effect on the transient contractions induced by beta-NADH nor the pyrogallol-induced abolishment of ACh-induced relaxation in WKY aortae. Flavone enhanced endothelium-independent relaxation to sodium nitroprusside (SNP) in both endothelium-intact and -denuded WKY aortae. Flavone enhanced relaxation to ACh and SNP as well as attenuated contractile effects to PE in SHR and diabetic aortae, a finding similar to that observed in normal WKY aortae. From these results, we conclude that flavone modulates vascular reactivity in normal as well as hypertensive and diabetic aortae. These effects of flavone results probably through enhanced bioactivity of nitric oxide released from the endothelium.
authors.affiliation: Department of Pharmacology, University of Malaya, Kuala Lumpur, Malaysia. ajayphd_2006@yahoo.com
authors.forename: Machha
authors.initials: M
authors.lastname: Ajay
authors.forename: Francis I
authors.initials: FI
authors.lastname: Achike
authors.forename: Mohd Rais
authors.initials: MR
authors.lastname: Mustafa
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006152:Cyclic GMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009243:NAD / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D047309:Flavones; D005419:Flavonoids; D014665:Vasodilator Agents; D009243:NAD; D009599:Nitroprusside; D009569:Nitric Oxide; D011189:Potassium Chloride; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D000109:Acetylcholine; C043562:flavone; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin