title: Vasorelaxing and antihypertensive effects of 7,8-dihydroxyflavone.
abstract: BACKGROUND
  Although 7,8-dihydroxyflavone (7,8-DHF) has been demonstrated to be potently neuroprotective, its effect on vascular function remains unknown.
  
  
  METHODS
  The effect of 7,8-DHF on phenylephrine (PE)-induced preconstriction was examined with aortic rings isolated from normal rats. Its effective mechanisms were studied with blockers, Western blotting, and primarily cultured vascular smooth myocytes. The blood pressure (BP) of rats was measured with a tail cuff method.
  
  
  RESULTS
  7,8-DHF dose-dependently dilated the PE-preconstricted, endothelia-intact aortic rings with concentration for 50% of maximal effect (EC50) of approximately 24 µM. Both Nω-nitro-L-arginine methyl ester hydrochloride, a nitric oxide synthase inhibitor, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a soluble guanylyl cyclase blocker, significantly reduced the vasorelaxing effect of 7,8-DHF. Western blotting showed that 7,8-DHF increased the aortic endothelial nitric oxide synthase protein expression and phosphorylation. With endothelia removed, 7,8-DHF also dilated the PE-preconstricted rings but with EC50 of approximately 104 µM. Ca(2+) imaging experiments detected that 7,8-DHF probably blocked both intracellular Ca(2+) release and extracellular Ca(2+) influx. Therefore, the mechanisms of 7,8-DHF dilating effect might be stimulating the nitric oxide/cGMP production and blocking the Ca(2+) signaling pathway instead of tropomyosin receptor kinase B receptors because ANA-12, its specific antagonist, did not show any effect against 7,8-DHF. When administered intravenously, 7,8-DHF significantly reduced the BP of the spontaneously hypertensive rats. However, when used orally, there was only a slight but significant reduction in the diastolic pressure.
  
  
  CONCLUSIONS
  The results suggest that neuro-protective 7,8-DHF is also a vasorelaxing and antihypertensive substance in rats.
authors: Department of Physiology, Qingdao University Medical College, Qingdao, China.
authors: Ruituo
authors: R
authors: Huai
authors: Xiaohua
authors: X
authors: Han
authors: Bingxiang
authors: B
authors: Wang
authors: Chunlin
authors: C
authors: Li
authors: Yawen
authors: Y
authors: Niu
authors: Ran
authors: R
authors: Li
authors: Zhiqiang
authors: Z
authors: Qu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D047309:Flavones / Q000008:administration & dosage / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D007275:Injections, Intravenous; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D011918:Rats, Inbred SHR; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C485383:6,7-dihydroxyflavone; D000959:Antihypertensive Agents; D047309:Flavones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D006152:Cyclic GMP
keywords: 7,8-dihydroxyflavone; antihypertensive; aorta; blood pressure; hypertension; vasorelaxant.