Vascular myorelaxing activity of isolates from South African Hyacinthaceae partly mediated by activation of soluble guanylyl cyclase in rat aortic ring preparations.
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.
Fusi
Fabio
F
Dipartimento di Scienze Biomediche, Università degli Studi di Siena, via A. Moro 2, 53100 Siena, Italy. fusif@unisi.it
Ferrara
Antonella
A
Koorbanally
Chantal
C
Crouch
Neil R
NR
Mulholland
Dulcie A
DA
Sgaragli
Giampietro
G
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*
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