RAT AORTIC VASOREACTIVITY IS ALTERED BY OLD-AGE AND HINDLIMB UNLOADING

Prolonged bed rest in young adults leads to a number of cardiovascular alterations, including orthostatic intolerance and decreased exercise capacity. Similar changes occur with advanced age. These modifications of cardiovascular function have been suggested to be causally related to changes in peripheral vascular reactivity. Using rat hindlimb unloading as an animal model of physical inactivity, this study was designed to determine whether prolonged decreases in weight-bearing activity induce changes in vascular reactivity that are similar to those occurring in senescent rats and whether the imposition of inactivity on old rats further modifies any age-related alterations in vasomotor responsiveness. Responses to vasoactive compounds were examined in vitro by using isolated abdominal aortic rings. Maximal isometric contractile force evoked by the vaso-constrictors KCl, norepinephrine (NE), and arginine vasopressin was lower in aortic segments from young hindlimb-unloaded (YHU), old control (OC), and old hindlimb-unloaded (OHU) rats compared with that from young control (YC) rats. Sensitivity [mean effective concentration (EC(50))] to KCl was enhanced in segments from both old and unloaded animals compared with YC rats, but EC(50) values for the other constrictors were not different among groups. Vasorelaxation responses induced by acetylcholine (10(-7) M NE preconstriction) were lower in vessel rings from OC (1 x 10(-7) to 3 x 10(-6) M), YHU (10(-7) to 10(-5) M), and OHU (10(-7) to 10(-5) M) rats than those from YC animals. In addition, vessel rings from OC, YHU, and OHU rats were less sensitive to sodium nitroprusside-induced relaxation. This study demonstrates that both physical inactivity via hindlimb unloading and old age result in similar alterations in vascular responsiveness. In addition, the imposition of reduced activity on old rats is of little further consequence. These results indicate that 2 wk of hindlimb unloading-induced inactivity in young animals is associated with alterations in vascular reactivity that are equivalent to those in vessels from old animals.