Vascular hyporesponsiveness in simulated microgravity: role of nitric oxide-dependent mechanisms

Simulated microgravity depresses the ability of arteries to constrict to no repinephrine (NE). In the present study the role of nitric oxide-dependent mechanisms on the vascular hyporesponsiveness to NE was investigated in per ipheral arteries of the rat after 20 days of hindlimb unweighting (HU). Blo od vessels from control rats and rats subjected to HU (HU rats) were cut in to 3-mm rings and mounted in tissue baths for the measurement of isometric contraction. Mechanical removal of the endothelium from carotid artery ring s, but not from aorta or femoral artery rings, of HU rats restored the cont ractile response to NE toward control. A 10-fold increase in sensitivity to ACh was observed in phenylephrine-precontracted carotid artery rings from HU rats. In the presence of the nitric oxide synthase (NOS) substrate L-arg inine, the inducible NOS inhibitor aminoguanidine (AG) restored the contrac tile responses to NE to control levels in the femoral, but not carotid, art ery rings from HU rats. In vivo blood pressure measurements revealed that t he peak blood pressure increase to NE was significantly greater in the cont rol than in the HU rats, but that to AC; was less than one-half in control compared with HU rats. These results indicate that the endothelial vasodila tor mechanisms may be upregulated in the carotid artery, whereas the induci ble NOS expression/activity may be increased in the femoral artery from HCT rats. These HU-mediated changes could produce a sustained elevation of vas cular nitric oxide levels that, in turn, could contribute to the vascular h yporesponsiveness to NE.