Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice

Abstract

Whether myocardial contractile impairment contributes to orthostatic intolerance (OI) is controversial. Accordingly, we used transient bilateral carotid occlusion (TBCO) to compare the in vivo pressor, chronotropic, and inotropic responses (parts 1 and 2) to open-loop selective carotid baroreceptor unloading in anesthetized mice. In part 3, in vitro myocyte responses to isoproterenol in mice exposed to hindlimb unweighting (HLU) for approximately 2 wk were determined. Heart rate (HR) and mean arterial pressure (MAP) responses to TBCO were measured. In control mice, TBCO increased HR (15 +/- 2 beats/min, P < 0.05) and MAP (17 +/- 2 mmHg, P < 0.05). These responses were markedly potentiated in denervated control (DC) mice, in which the aortic depressor nerve and sympathetic trunk were sectioned before measurement. Baroreflex responses to TBCO were eliminated by blockade with hexamethonium bromide (10 microg/kg). In HLU (denervated) mice, HR and MAP responses were reduced approximately 70% compared with DC mice. In part 2, myocardial contractile responses to TBCO were measured with a left ventricular micromanometer-conductance catheter. TBCO in DC mice increased the slope of the end-systolic pressure-volume relation (end-systolic elastance) by 86 +/- 13%. This inotropic response was attenuated (14 +/- 10%, P < 0.005) after HLU. In part 3, contractile responses to isoproterenol were impaired in myocytes isolated from HLU mice. In conclusion, selective carotid baroreceptor unloading stimulates HR, blood pressure, and myocardial contractility, and HLU attenuates each response. These findings have important implications for the management of OI in astronauts, the elderly, and individuals subjected to prolonged bed rest.

Modulation of β-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats

“…One group of the rats (n ϭ 40) was subjected to tail suspension to simulate microgravity, while the control (n ϭ 40) was maintained in room air. The technique of tail suspension (22) with modification from our collaborative laboratory has been described in detail previously (13,20). The animals were maintained at about Ϫ30°head-down tilt with their hindlimbs unloaded.…”

“…The depressed contractility may be due to the changes of cardiac tissue, the low cardiovascular response to low circulating blood volume, and the impaired regulation of cardiac function. It is well known that ␤-adrenoceptor is a predominant receptor in regulation of cardiac function, and recent studies have suggested that the responsiveness of cardiac contractility to ␤-adrenoceptor stimulation is reduced after weightlessness (13,26).…”

Baroreflex Sensitivity Might Predict Responders to Milrinone in Patients With Heart Failure

“…Previous studies have suggested that arterial baroreflex control of HR is diminished in heart failure, 11,21) and that the contribution of baroreflex control in myocardial contractility is markedly impaired in animals with a lower baseline inotropic state. 22) Furthermore, in heart failure, baroreflex changes in cardiac output are less related to changes in HR and more related to changes in stroke volume. 23) Milrinone is considered to exert a positive inotropic action and to decrease left ventricular endsystolic pressure reflecting the decrease in left ventricular afterload.…”

Modulation of intracellular calcium transient in response to β-adrenoceptor stimulation in the hearts of 4-wk-old rats during simulated weightlessness

“…One group of rats (n ϭ 44) was subjected to tail suspension to simulate microgravity, whereas the control (normal group, n ϭ 44) was maintained at ambient air. The technique of tail suspension (3) with modifications from our collaborative laboratory has been previously described in detail (10,13). Animals were maintained at about Ϫ30°C head-down tilt, with their hindlimbs unloaded.…”

“…It is well known that the ␤-adrenoceptor is a predominant receptor in regulation of cardiac function. Recent studies suggested that the responsiveness of cardiac contractility to ␤-adrenoceptor stimulation is reduced after weightlessness (10,11). Depressed ␤-adrenoceptor responsiveness may be due to downregulation of the ␤-adrenoceptor itself or to the impaired postreceptor events.…”