Genistein, a phytoestrogen, possesses cardioprotective effects. Responses to genistein (0.1-100 microM) were assessed in 9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy prostaglandin F(2 alpha) (U46619)-contracted porcine coronary arterial rings, with significant relaxations at high concentrations. At concentrations with little relaxation, genistein (0.3-3 microM) did not affect relaxation produced by bradykinin and the calcium ionophore, A23187. In contrast, sodium nitroprusside- and cromakalim-induced relaxations were enhanced by genistein (3 microM). N(omega)-nitro-L-arginine methyl ester (L-NAME) (300 microM) or Triton X-100 (0.5%) did not affect the enhancement of relaxation by genistein. The tyrosine kinase inhibitor, tyrphostin 23 (30 microM), had no effect on sodium nitroprusside-elicited relaxation. In summary, genistein relaxed porcine coronary artery at relatively high concentrations. At a physiologically relevant concentration (3 microM), it is devoid of significant vascular effect, but enhanced endothelium-independent relaxations. This effect of genistein does not involve the nitric oxide synthase (NOS) pathway and the endothelium, and is mediated through a mechanism different from tyrosine kinase inhibition.