Selective vasodilator and chronotropic actions of 3',4'-dihydroxyflavonol in conscious sheep

Flavonoids are known to relax isolated large arteries, but the cardiovascular actions of flavonoids are not well studied in vivo. Hence, we determined the systemic and regional haemodynamic responses to a novel synthetic flavonol, 3',4'-dihydroxyflavonol (DiOHF), in conscious sheep previously instrumented with flow probes on the aorta and coronary, mesenteric, renal, and iliac arteries. Intravenous injection of DiOHF (1.0 mg/kg) caused a delayed but prolonged vasodilatation in the coronary and renal vascular beds, with no changes in the mesenteric or iliac vascular beds. DiOHF induced prolonged increases in heart rate and cardiac output without altering arterial pressure. Pretreatment with Nomega-nitro-L-arginine, a nonspecific inhibitor of nitric oxide synthase, abolished all the cardiovascular effects of DiOHF. The results indicate that DiOHF caused a nitric oxide-dependent vasodilatation of the coronary and renal vasculature and an increase in cardiac output due to its chronotropic action.