Evidence for increased beta-adrenoreceptor responsiveness induced by 14 days of simulated microgravity in humans

Abstract

We studied hemodynamic responses to alpha- and beta-receptor agonists in eight healthy men before and after 14 days of 6 degrees head-down tilt (HDT) to test the hypothesis that increased adrenoreceptor responsiveness is induced by prolonged exposure to simulated microgravity. Steady-state infusions of isoproterenol (Iso) at rates of 0.005, 0.01, and 0.02 microgram.kg-1.min-1 were used to assess beta 1- and beta 2-adrenoreceptor responsiveness. Infusions of phenylephrine (PE) at rates of 0.25, 0.50, and 1.00 microgram.kg-1.min-1 were used to assess responsiveness of alpha 1-vascular adrenoreceptors. Slopes calculated from linear regressions between Iso and PE doses and changes in beat-to-beat heart rate, blood pressure, and leg vascular resistance (occlusion plethysmography) for each subject were used as an index of alpha- and beta-adrenoreceptor responsiveness. HDT increased the slopes of heart rate (1,056 +/- 107 to 1,553 +/- 83 beats micrograms-1.kg-1.min-1; P = 0.014) and vasodilation (-469 +/- 111 to -1,446 +/- 309 peripheral resistance units.microgram-1.kg-1.min-1; P = 0.0224) to Iso infusion. There was no alteration in blood pressure or vascular resistance responses to PE infusion after HDT. Our results provide evidence that simulated microgravity causes selective increases in beta 1- and beta 2-adrenoreceptor responsiveness without affecting alpha 1-vascular adrenoreceptor responses.

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

“…It should be stated that the results in our present study in 4 wk HU rats are different from the results in head-down bed rest humans in previous studies (1,9). The data in these studies provided evidence that simulated microgravity for 5 or 14 days causes an increase in ␤-adrenoceptor responsiveness.…”

Contractile Responses of the Basilar Artery Isolated from Rabbits Exposed to 8-Day Head-Down Tilt.

“…Treatment with propranolol (a ␤-adrenergic antagonist) increased the contractile response to NE in the basilar arteries isolated from HDT rabbits, but not in those from control rabbits, which indicates that exposure to HDT enhances the activity of ␤-adrenergic receptors in the basilar arteries. This is consistent with the finding in vasodilator response of human leg vasculature [18]. It is known that ␤-adrenoceptor activity is accentuated in a condition where circulating catecholamines are reduced [19].…”

“…These results suggest that the NE-induced contraction of the rabbit basilar artery is induced mainly through activation of ␣ 1 -adrenergic receptors. Contractile responses to pheyleprine have been shown to decrease in the isolated aorta from rats exposed to hind-limb unloading [12], but not in leg vasculature of humans during HDT [18]. In the present study, phenylephrine-induced contraction of the rabbit basilar artery was smaller in the HDT group than in the control group, suggesting that activity of ␣ 1 -adrenergic receptors is related to the mechanism of decreased NE response.…”

Loss of resting bradycardia with detraining is associated with intrinsic heart rate changes

“…A significant decline in cardiovascular function and muscle metabolic potential occurs with days or weeks of detraining and is associated with a significant reduction in peak VO 2 (3) .…”