VASOCONSTRICTOR PROPERTIES OF RAT AORTA ARE DIMINISHED BY HINDLIMB UNWEIGHTING

Prolonged bed rest and exposure to weightlessness in humans result in cardiovascular alterations that are characterized by orthostatic intol erance and decreased exercise capacity. Modifications of cardiovascula r function have been suggested to be causally related to changes in pe ripheral vascular reactivity. Rat hindlimb unweighting (HU) was used a s an animal model to determine whether prolonged decreases in weight-b earing activity induce changes in vasoreactivity of peripheral arteria l vessels. Responses to vasoactive compounds were examined in vitro us ing isolated abdominal and thoracic aortic rings. Maximal isometric co ntractile tension evoked by the vasoconstrictors KCl (10-100 mM), nore pinephrine (NE; 10(-9)-10(-4) M), phenylephrine (10(-9)-10(-4) M), arg inine vasopressin (10(-13)-3 X 10(-5) M), and CaCl2 (10(-6)-10(-2) M) was lower in abdominal aortic rings from HU rats. Sensitivity [agonist concentration that produced 50% of maximal vasoconstrictor response ( EC50)] to KCl was enhanced in segments from HU animals but was not dif ferent for the other constrictors. Maximal contractile responses of th oracic aortic rings to KCl (10-100 mM) and NE (10(-4)-10(-4) M) were a lso attenuated by HU. In abdominal aortic rings preconstricted with 10 (-4) M NE, maximal vasodilatory responses induced by sodium nitropruss ide (10(-10)-10(-4) M) and 8-bromoguanosine 3',5'-cyclic monophosphate (10(-6)-10(-2) M) were greater in vessel rings from HU rats. However, with 10(-7) M NE preconstriction, maximal dilatory responses induced by sodium nitroprusside (10(-10)-10(-4) M) and acetylcholine (10(-9)-1 0(-4) M) were not different between groups. These data indicate that p rolonged decreases in weight-bearing activity result in a compromised ability of aortic smooth muscle to produce contractile tension and may be causally related to the cardiovascular alterations associated with prolonged inactivity and weightlessness.