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U-51605, A PROSTACYCLIN SYNTHASE INHIBITOR, BLOCKS POST-SUSPENSION HYPOTENSION IN SPRAGUE-DAWLEY RATS.   M.A. Bayorh, D. Eatman, M. Walton, R.R. Socci and N. Emmett.  Morehouse School of Medicine, Atlanta, GA.

     Orthostatic hypotension is frequently manifested in astronauts during standing postflight.  To evaluate the role of the prostacyclin synthase inhibitor U-51605 as a countermeasure against post-suspension hypotension, we examined the cardiovascular responses to 7 day 30^o tail-suspension and a subsequent 6 hr post-suspension period in conscious male Sprague-Dawley rats.  U-51605 (0.3 mg/kg, i.v.) or saline were injected prior to release from suspension and at 2 and 4 hrs post-suspension.  During suspension, MAP did not change, in contrast, at 6 hrs post-suspension, it decreased compared to parallel tethered (control) animals. U-51605 attenuated the observed post-suspension hypotension without alteration in heart rate. Both plasma prostacyclin and nitric oxide were elevated post-suspension, but only prostacyclin was reduced by U-51605. Plasma levels of thromboxane and prostaglandin E₂ were not altered post-suspension.  Baroreflex sensitivity for heart rate was modified by U-51605.  Thus, simulated microgravity and the subsequent post-suspension recovery are associated with excessive production of endothelium-dependent relaxing factors (i.e., prostacyclin and nitric oxide).  These observations may lead to the development of more effective countermeasures for astronauts.  

     (Supported by NASA grant NCC-9-112 and NIH grants S06GM08248-12 and NIGMS-GM58268.)