Post-suspension hypotension is attenuated in Sprague-Dawley rats by prostacyclin synthase inhibition.
Cardiovascular deconditioning, sometimes manifested in astronauts during standing postflight, may be related to the impairment of autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, we examined the cardiovascular responses to 7-day 30 degrees tail-suspension and a subsequent 6-h post-suspension period in conscious male Sprague-Dawley rats to determine the role of prostacyclin in the observed post-suspension reduction in mean arterial pressure (MAP). The specific prostacyclin synthase inhibitor U-51605 (0.3 mg/kg), or saline, was administered intravenously prior to release from suspension and at 2 and 4 h post-suspension. During 7 days of suspension, MAP did not change, however, there was a post-suspension reduction in MAP which was associated with significant increases in plasma prostacyclin and nitric oxide. U-51605 attenuated the observed post-suspension hypotension and reduced plasma prostacyclin levels, but not nitric oxide levels. The baroreflex sensitivity for heart rate was modified by U-51605: increased MAP threshold and effective MAP range. Thus, the post-suspension reduction in mean arterial pressure may be due to overproduction of prostacyclin and/or other endothelium-dependent relaxing factors and alteration in baroreflex activity.
Bayorh
M A
MA
Department of Pharmacology Toxicology, Morehouse School of Medicine, Atlanta, Georgia 30310-1495, USA. bayorh@msm.edu
Eatman
D
D
Walton
M
M
Socci
R R
RR
Emmett
N
N
D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018493:Cardiovascular Deconditioning; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000097:blood; D018475:Head-Down Tilt; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D019417:Hindlimb Suspension; D007024:Hypotension, Orthostatic / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D011463:Prostaglandins H / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D018474:Weightlessness Simulation / Q000009:adverse effects
D065607:Cytochrome P-450 Enzyme Inhibitors; D015777:Eicosanoids; D011463:Prostaglandins H; D009569:Nitric Oxide; C015014:azo analog I; D003577:Cytochrome P-450 Enzyme System; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase
NASA Discipline Cardiopulmonary; Non-NASA Center