title: Vascular myorelaxing activity of isolates from South African Hyacinthaceae partly mediated by activation of soluble guanylyl cyclase in rat aortic ring preparations.
abstract: The vasorelaxing effect of isolates (compounds 1, 2, 3, and 4 (homoisoflavanones), compound 5 (sesquiterpenoid), compounds 6 and 7 (bufadienolides)) from the South African Hyacinthaceae has been assessed using rat aortic ring preparations. Compounds 2, 3, and 4 inhibited the tonic contraction induced by both 60 mM K(+) (K60) and phenylephrine, compound 3 being the most potent. Compounds 5, 6, and 7 caused a modest concentration-dependent relaxation, whereas compound 1 was ineffective. Under K25- or K60-induced depolarization, compound 3 displayed antispasmodic effects not reversed by tetraethylammonium. Under precontraction induced with phenylephrine, compound 3 shifted to the left the concentration-relaxation curves of either isoprenaline or sodium nitroprusside. 1 H-[1,2,4] oxidazolol [4,3-a] quinoxalin-1-one shifted to the right the concentration-relaxation curve of compound 3, while 3'-isobutyl-1-methylxanthine had no effect. In the absence of extracellular Ca(2+), compound 3 (estimated pIC50 = 4.66) and ryanodine reduced the response to phenylephrine. Phenylephrine-stimulated influx of extracellular Ca(2+) was markedly reduced when tissues were pretreated with compound 3 (pIC50 = 5.14) or nifedipine, but stimulated by ryanodine. Compound 3 partially antagonized the contraction induced by phorbol 12-myristate-13-acetate. To our knowledge, this has been the first account describing the vasodilating activity of homoisoflavonoids: compound 3 proved an effective vasorelaxing agent, partly acting via the activation of soluble guanylyl cyclase.
authors.affiliation: Dipartimento di Scienze Biomediche, Università degli Studi di Siena, via A. Moro 2, 53100 Siena, Italy. fusif@unisi.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Fusi
authors.forename: Antonella
authors.initials: A
authors.lastname: Ferrara
authors.forename: Chantal
authors.initials: C
authors.lastname: Koorbanally
authors.forename: Neil R
authors.initials: NR
authors.lastname: Crouch
authors.forename: Dulcie A
authors.initials: DA
authors.lastname: Mulholland
authors.forename: Giampietro
authors.initials: G
authors.lastname: Sgaragli
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002018:Bufanolides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007529:Isoflavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019668:Liliaceae / Q000737:chemistry*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D017680:Potassium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013019:South Africa; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: C529644:(R)-3',5-dihydroxy-4',7-dimethoxyspiro(2H-1-benzopyran- 3(4H),7'-bicyclo(4.2.0)-octa(1,3,5)-trien)-4-one; D002018:Bufanolides; D007529:Isoflavones; D010936:Plant Extracts; D015221:Potassium Channels; D017680:Potassium Compounds; D012717:Sesquiterpenes; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; C016658:phorbolol myristate acetate; D006162:Guanylate Cyclase; D013755:Tetradecanoylphorbol Acetate