Effects of genistein and daidzein on enhanced vascular contractile reactivity and Ca2+ sensitivity in cardiomyopathic hamsters.
We investigated the contribution of tyrosine kinase activity to the enhanced vasoreactivity in cardiomyopathic (CM) hamsters. The contractile response of the aorta to phenylephrine was greatly enhanced in CM in comparison to control hamsters. Genistein, a tyrosine kinase inhibitor, did not affect the maximum contractile response to phenylephrine in control aortas, although the sensitivity to phenylephrine was significantly diminished. In contrast, genistein markedly inhibited both the sensitivity and the maximum contractile response to phenylephrine in CM aortas. Daidzein, an inactive form of genistein, also inhibited the sensitivity to phenylephrine in both strains although the maximum contractile response was not altered even in the CM aorta. The Ca2+ sensitivity of tension was significantly augmented in alpha toxin-permeabilized smooth muscle from the mesenteric artery of CM hamsters. Furthermore, phenylephrine enhanced myofilament sensitivity to Ca2+ more in CM than control hamsters. The enhancement of myofilament Ca2+ sensitivity by phenylephrine was markedly inhibited by genistein only in CM hamsters. The inhibition by daidzein of the phenylephrine effect on the Ca2+ sensitivity in CM hamsters was less pronounced. These results suggest that an increase in tyrosine kinase activity may lead to enhanced vascular reactivity in CM hamsters possibly due to an increased Ca2+ sensitivity of the contractile apparatus.
Sato
A
A
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan. asato@med.hokudai.ac.jp
Hattori
Y
Y
Kanno
M
M
D000818:Animals; D001011:Aorta; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000201:enzymology* / Q000378:metabolism; D006224:Cricetinae; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries; D008647:Mesocricetus; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; C004742:daidzein; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D002118:Calcium