Effects of the flavonoid quercetin and its methylated metabolite isorhamnetin in isolated arteries from spontaneously hypertensive rats.
Chronic oral quercetin exerts antihypertensive effects in spontaneously hypertensive rats (SHR). In the present study, the vasodilator effects of the flavonoid quercetin and its main metabolite isorhamnetin were analysed in isolated thoracic aorta, iliac artery and on the isolated perfused mesenteric resistance vascular bed from SHR and normotensive Wistar Kyoto rats (WKY). In noradrenaline-precontracted vessels from SHR there was an inverse correlation between the relaxant potency (pIC50) of quercetin (4.76 +/- 0.02, 5.08 +/- 0.12, 5.30 +/- 0.18, in aorta, iliac arteries and mesentery, respectively) and isorhamnetin (4.90 +/- 0.11, 5.38 +/- 0.15 and 5.80 +/- 0.10, respectively) and the diameter of the vessel studied. Both flavonoids were more potent in endothelium-denuded aortae and iliac arteries from SHR than from normotensive WKY rats. In addition, in aortae from SHR both flavonoids restored the endothelial-dependent vasodilation. Isorhamnetin, but not quercetin, also reduced the endothelium-dependent contractile responses induced by acetylcholine. These direct vasodilator effects, together with the improvement of endothelial function, are good candidates to explain the blood pressure reduction and vascular protective effects of quercetin in animal models of hypertension and possibly in human cardiovascular diseases.
Ibarra
Manuel
M
Department of Pharmacology, Institute of Pharmacology and Toxicology (CSIC), School of Medicine, University Complutense of Madrid, Spain.
Moreno
Laura
L
Vera
Rocío
R
Cogolludo
Angel
A
Duarte
Juan
J
Tamargo
Juan
J
Perez-Vizcaino
Francisco
F
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D044948:Flavonols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007083:Iliac Artery / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008297:Male; D008517:Phytotherapy; D010946:Plants, Medicinal; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000187:drug effects*
D000959:Antihypertensive Agents; D044948:Flavonols; C047368:3-methylquercetin; D011794:Quercetin