Depressed responsiveness of cardiomyocytes to isoproterenol in simulated weightlessness rats / 生理学报

ABSTRACT

The present study aimed to observe the changes of contractile function and responsiveness to isoproterenol (ISO) in tail-suspended rat cardiomyocytes under simulated weightlessness condition. Tail-suspended rat model was used to simulate weightlessness on the ground. Twenty-four male Sprague-Dawley rats were randomly divided into the control and tail-suspended groups. After 4 weeks of suspension, the rats were injected with heparin (100 IU/100 g body weight, i.p.) and anesthetized with pentobarbital sodium (40 mg/kg body weight). The hearts were removed and the aortas were cannulated rapidly. The cannulated hearts were mounted on a Langendorff perfusion apparatus and perfused with constant flow. The perfusion pressure was monitored. The hearts were digested by 0.08% collagenase I at 37 degrees C. The ventricular tissues were chopped and the single myocytes were dispersed gently by a wide-tipped pipette. The contractile function was measured in the Edge Detector system within 6 h after isolation. The length and width of cardiomyocytes were measured without electric stimulation. Contractile curves of the single cardiomyocytes were recorded at stimulation frequency of 1.0, 2.0 and 4.0 Hz. To observe the responsiveness of cardiomyocytes to ISO, 1, 5 and 10 nmol/L ISO in Kreb's solution was perfused at a stimulation frequency of 2.0 Hz. The length and width of the left and right ventricular cardiomyocytes in tail-suspended group had little difference from that in the control group. The unloaded shortening amplitude increased as stimulation frequency elevated in both the control and tail-suspended groups. It was increased by (8.50±1.26)%, (9.00±1.38)%, (9.23±1.83)% in the left ventricular cardiomyocytes, and (9.80±2.48)%, (10.03±2.48)%, (10.28±2.27)% in the right ventricular cardiomyocytes in the control group at stimulation frequency of 1.0, 2.0 and 4.0 Hz. Compared with that in the control group, the unloaded shortening amplitude decreased by 12.2% and 10.9% in the left ventricular cardiomycytes (P<0.05), and 16.5% and 16.3% in the right ventricular cardiomyocytes (P<0.05) at stimulation frequency of 1.0 and 2.0 Hz in tail-suspended group. There was no significant difference in unloaded shortening amplitude at stimulation frequency of 4.0 Hz between the control and tail-suspended groups. Time to peak shortening (TPS) in tail-suspended group significantly reduced in both the left and right ventricular cardiomyocytes (P<0.05). Time from peak to 75% relaxation (TR(75)) in tail-suspended group significantly prolonged in both the left and right ventricular cardiomyocytes (P<0.05). No significant differences in shortening and relaxation rate (±dL/dt(max)) were observed between the control and tail-suspended groups. The unloaded shortening amplitude increased by (10.63±0.83)%, (35.06±5.22)% and (71.64±6.83)% in the control cardiomyocytes, but increased by (5.75±0.76)%, (23.97±4.50)% and (26.38±8.13)% in tail-suspended group during perfusion with 1, 5 and 10 nmol/L ISO (P<0.05, P<0.01). The unloaded shortening amplitude increased by (3.04±0.27)%, (9.81±2.66)% and (20.20±3.47)% in the control cardiomyocytes, but increased by (1.42±0.53)%, (3.83±1.71)% and (5.49±4.08)% in tail-suspended group during perfusion with 10, 50 and 100 nmol/L forskolin (P<0.05). The results obtained suggest that the unloaded shortening amplitude and responsiveness to ISO decrease in rat cardiomyocytes after 4-week tail-suspension.