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 modification
s of cardiovascular function have been suggested to be causally relate
d to changes in peripheral vascular reactivity. Using rat hindlimb unl
oading as an animal model of physical inactivity, this study was desig
ned to determine whether prolonged decreases in weight-bearing activit
y induce changes in vascular reactivity that are similar to those occu
rring in senescent rats and whether the imposition of inactivity on ol
d rats further modifies any age-related alterations in vasomotor respo
nsiveness. 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 ar
ginine vasopressin was lower in aortic segments from young hindlimb-un
loaded (YHU), old control (OC), and old hindlimb-unloaded (OHU) rats c
ompared with that from young control (YC) rats. Sensitivity [mean effe
ctive concentration (EC(50))] to KCl was enhanced in segments from bot
h old and unloaded animals compared with YC rats, but EC(50) values fo
r the other constrictors were not different among groups. Vasorelaxati
on responses induced by acetylcholine (10(-7) M NE preconstriction) we
re 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 Y
C animals. In addition, vessel rings from OC, YHU, and OHU rats were l
ess sensitive to sodium nitroprusside-induced relaxation. This study d
emonstrates that both physical inactivity via hindlimb unloading and o
ld age result in similar alterations in vascular responsiveness. In ad
dition, the imposition of reduced activity on old rats is of little fu
rther consequence. These results indicate that 2 wk of hindlimb unload
ing-induced inactivity in young animals is associated with alterations
in vascular reactivity that are equivalent to those in vessels from o
ld animals.