Virtually every blood vessel in the body is surrounded to some degree by adipose tissue. A potential role for perivascular adipose tissue as a neurohumoral regulator of vascular responsiveness was studied. Thoracic aortae obtained from male Sprague-Dawley rats were cut into rings for use in a standard in vitro smooth muscle bath set-up. The vessels were either cleaned of surrounding adipose tissue or left intact. Contractile responses to KCl and phenylephrine as well as relaxation responses to acetylcholine, isoproterenol and sodium nitroprusside were not different between cleaned and intact tissues. However, a significant decrease in the sensitivity to norepinephrine was observed in intact vessels. This altered response was corrected by prior treatment with desipramine plus deoxycorticosterone. Contractile responses of aortic ring preparations to tyramine and a potassium-free physiological solution were significantly greater in intact tissues. Electrical stimulation resulted in no response in cleaned tissues, however, a frequency-dependent contraction was elicited in intact vessels. Phentolamine blocked the contractile responses generated by these manipulations which activate the sympathetic neuroeffector system. Responses evoked by electrical stimulation in intact vascular preparations were significantly attenuated by prior exposure to the selective angiotensin II (AII) antagonist SarI-Ile8-AII. These observations demonstrate that perivascular adipose tissue significantly influences vascular responsiveness in the in vitro setting.

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Although calcitonin (CT) has been shown to be effective for the prevention of bone loss in early postmenopausal women, the skeletal effects of the hormone specifically during the early stages of estrogen deficiency have not been characterized histomorphometrically to date. The current study involves use of the ovariectomized (OVX) rat as an animal model for early postmenopausal bone loss to perform such a histomorphometric analysis. One group of OVX rats was injected sc with salmon CT on alternate days for a 6-week period. Additional groups of OVX and sham-operated control rats were treated with vehicle alone. In comparison to control rats, the proximal tibia of vehicle-treated OVX rats were characterized by a 3-fold decrease in cancellous bone volume and significant increases in osteoblast surface (+200%), osteoclast surface (+143%), mineralizing surface (+111%), mineral apposition rate (+36%), bone formation rate (+181%), and longitudinal bone growth (+38%). In contrast, treatment of OVX rats with CT normalized tibial cancellous bone volume and significantly decreased all of the above cellular- and fluorochrome-based indices of bone turnover to near control levels. The results indicate that CT treatment depresses bone turnover and prevents the development of osteopenia in OVX rats. These findings are consistent with the bone protective effect of CT in early postmenopausal women and further support the OVX rat as an animal model for the preclinical evaluation of prophylactic treatments for postmenopausal bone loss.

Alterations in endothelium-dependent, sodium pump-mediated, and calcium-dependent responses of vascular smooth muscle were investigated in 5-7-, 24-26-, and 50-52-week-old male Sprague-Dawley rats. Age-dependent changes in systolic blood pressure were also determined. Although systolic blood pressure increased significantly with age, rats in all 3 age groups were considered normotensive. Initial studies on the passive force-response characteristics of strips of aortic and femoral arterial smooth muscle revealed that the level of passive force required for maximum active tension generation increased with increasing age. Subsequent studies were carried out using optimum passive force requirements. Endothelium-dependent relaxations of aortic smooth muscle induced by acetylcholine and the calcium ionophore A23187 decreased significantly with increasing age. An age-dependent decrease in the contractile response of aortic smooth muscle to ouabain and potassium-free physiological salt solution (PSS) was observed. Potassium relaxation of femoral smooth muscle following contraction to norepinephrine (NE) in a potassium-free PSS was also significantly attenuated with increasing age. No age-related alterations in calcium sensitivity (in the presence of 10~7 M NE) or calcium relaxation (membrane stabilization) of femoral arterial smooth muscle was seen. These results show that endothelium-dependent and sodium pump-mediated responses are reduced in vascular smooth muscle of the rat with increasing age. However, no changes in calcium-dependent responses are apparent. These observations are discussed in relation to the vascular changes observed in hypertension. (Circulation Research 1988;62:889-897)