Cardiovascular Effects of Hind-limb Unweighing in Mice

Background: Orthostatic intolerance is a debilitating problem that can occur after prolonged bed-rest, exposure to microgravity, and in the elderly.This study examined the integrated cardiovascular response to baroreceptor activation in a hind-limb unweighing (HLU) mouse model of microgravity to test the hypothesis that both the pressor and contractility response are attenuated in HLU mice.Methods: C57BL/6 mice (25-30 g body wt, 8-10 wk old) were exposed to HLU for 2 weeks.A bilateral carotid artery occlusion and open-loop baroreceptor stimulus was performed to measure the myocardial contractile responses using a left ventricular micromanometer-conductance catheter in the mice.In isolated myocytes simultaneous sarcomere shortening and calcium transient were measured in response to increasing concentrations of the β-agonist isoproterenol.Results: In the controls, bilateral carotid artery occlusion increased the heart rate and mean arterial pressure.These responses were markedly attenuated in the HLU mice.A bilateral carotid artery occlusion also increased the slope of the end-systolic pressure volume relationship (Ees) by 70 ± 11% and the slope was markedly attenuated to 10 ± 8% in the HLU mice.Isoproterenol increased the sarcomere shortening in both control and HLU mice in a dose-dependent manner.However the contractile response to isoproterenol was significantly attenuated in the HLU mice than the controls.Conclusions: Both the pressor and myocardial contractile responses appear to be impaired in a mouse model of microgravity.(