Although both epidemiological and experimental evidence suggests that estrogen replacement therapy reduces the risk of coronary heart disease, the mechanisms for this beneficial effect are largely unknown. Furthermore, the addition of progestins or androgens to estrogen replacement therapy is of concern. The objective of this study was to examine the effects of esterified estrogens alone or in combination with an androgen on arterial LDL metabolism and early atherogenesis in ovariectomized female cynomolgus monkeys. Arterial LDL metabolism was assessed by using dual-labeled LDL that was injected 24 hours before necropsy. Arterial LDL degradation was reduced by 64% to 84% and cholesteryl ester content was decreased by approximately 50% in the thoracic aorta in both treatment groups compared with controls. In addition, aortic lipid peroxidation products, as assessed by thiobarbituric acid reaction, were significantly lower in animals treated with esterified estrogens, with a similar trend for combined estrogen-androgen treatment. Both treatments also reduced plasma concentrations of apoB-containing lipoproteins, reduced LDL particle size, and increased total-body LDL catabolism. The combination of decreased arterial LDL metabolism, decreased arterial lipid peroxidation, and improved plasma lipoprotein metabolism may explain some of the protective effects of estrogens on coronary heart disease and indicate that beneficial actions extend to a combination of estrogen and androgen.

SK&F 82526 is a potent renal vasodilator in dogs, monkeys, and hypertensive rats. It is orally active and has a specificity for the renal vasculature greater than dopamine. Its activity is owing, at least in part, to stimulation of renal dopamine receptors and has no effect on a-or p-adrenergic receptors. This compound should be valuable in further examining the importance of renal blood flow in essential hypertension.

SUMMARY1. The thermoregulatory characteristics of the neurogenic hyperthermia produced in rats by unilateral mechanical destruction of the rostral hypothalamic/preoptic region were studied.2. The investigational methods employed included (a) observing the thermoregulatory effector activities which were responsible for generation of hyperthermia, (b) observing the thermoregulatory reactions elicited by forcefully elevating or lowering core temperature during neurogenic hyperthermia and (c) observing the effect of ambient temperature on hyperthermia magnitude.3. At 26 0C, hyperthermia was effected by a transient increase in shivering thermogenesis and a concomitant minimization of heat loss through the tail.4. At 26 0C, perturbations of core temperature during the plateau phase of hyperthermia were induced by internal or external heating and cooling. The disturbances elicited compensatory changes in shivering activity and in tail vasomotor tonus, and core temperature was rapidly and precisely returned to its pre-perturbation level.5. The magnitudes of hyperthermias experienced by rats lesioned at 10, 15, 26 and 32 0C, as measured by the change in colonic temperature and by the area under the fever curve, were not significantly different. At 360C, rats were hyperthermic prior to lesioning, and the magnitude of the lesion-induced hyperthermia was significantly attenuated. 6. The results indicate that the neurogenic hyperthermia produced by unilateral hypothalamic puncture in the rat is generated by a coordinated modulation of thermogenic and heat retentive effectors and that the plateau level of hyperthermia is well regulated. These characteristics are compatible with the hypothesis that neurogenic hyperthermia is mediated by prostaglandins released from injured tissue and acting on surviving rostral hypothalamic tissue.

No abstract