MICROTUBULES MODULATE CARDIOMYOCYTE BETA-ADRENERGIC RESPONSE IN CARDIAC-HYPERTROPHY

The role of microtubules in modulating cardiomyocyte beta-adrenergic r esponse was investigated in rats with cardiac hypertrophy Male Sprague -Dawley rats underwent stenosis of the abdominal aorta (hypertensive, HT) or sham operation (normotensive, NT). Echocardiography and isolate d left ventricular cardiomyocyte dimensions demonstrated cardiac hyper trophy in the HT rats after 30 wk. Cardiomyocyte microtubule fraction was assayed by highspeed centrifugation and Western blot. In contrast to previous reports of increased microtubules after acute pressure ove rload, microtubule fraction for HT was significantly lower than that f or NT. Cardiomyocytes were exposed to either 1 mu M colchicine, 10 mu M taxol, or equivalent volume of vehicle. Colchicine decreased microtu bules, and taxol increased microtubules in both groups. Cardiomyocyte cytosolic calcium ([Ca2+](c)) and shortening/relaxation dynamics were assessed during exposure to increasing isoproterenol concentrations. T he beta-adrenergic response for these variables in the HT group was bl unted compared with NT. However, increased microtubule assembly by tax ol partially recovered the normal beta-adrenergic response for time to peak [Ca2+](c), time to peak shortening, and mechanical relaxation va riables. Microtubule assembly may play a significant role in determini ng cardiomyocyte beta-adrenergic response in chronic cardiac hypertrop hy.