Simulated microgravity enhances vasoconstrictor responsiveness of rat basilar artery

Recently, hypertrophy and increased myogenic tone of brain vessels have bee n observed in rats after simulated microgravity. It is expected that simula ted microgravity may also induce hyperreactivity of brain vessels. To test this hypothesis, Sprague-Dawley rats were subjected to a 4-wk tail-suspende d hindlimb unloading (TS) to simulate the cardiovascular deconditioning eff ect of microgravity. After 4 wk, the vasoreactivity of isolated basilar art erial rings from TS rats to both receptor- and non-receptor-mediated vasoco nstrictors, such as KCl, arginine vasopressin, or 5-hydroxytryptamine (5-HT ), and vasodilators such as ACh, thrombin, adenosine, or sodium nitroprussi de were examined and compared with those from simultaneous control (Cn) rat s. In the first part of this study, it was found that the maximal isometric contractile responsiveness evoked by vasoconstrictors such as KCl, arginin e vasopressin, or 5-HT was enhanced in basilar arterial rings from TS rats, whereas vasodilatory responsiveness to vasodilators showed no significant difference between TS and Cn rats. In the second part of this study, it was found that removal of the endothelium had no effects on the contractile re sponsiveness to 5-HT in basilar arterial rings from TS rats but enhanced ma rkedly the responsiveness in basilar arterial rings from Cn rats to an exte nt comparable with that of TS rats. Application of tetraethylammonium also had no effects on the contractile response to 5-HT in basilar arterial ring s from TS but significantly increased the responsiveness of basilar arteria l rings from Cn rats with endothelium intact. These results showed that 4-w k simulated microgravity enhanced the vascular contractile responsiveness o f basilar arterial rings to both receptor- and non-receptor-mediated vasoco nstrictors, and the enhancement of 5-HT-induced contraction in TS rat basil ar arteries was due to an impairment of endothelium-dependent mechanism. Th ese results suggest that endothelium-derived hyperpolarizing factors are re sponsible for this endothelium-dependent attenuating modulatory mechanism i n contractile responsiveness of rat basilar arteries to 5-HT.