Simvastatin and dehydroepiandrosterone sulfate effects against hypoxic pulmonary hypertension are not additive.

Pulmonary hypertension is a group of disorders characterized by elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance. To test our hypothesis that combining two drugs useful in experimental pulmonary hypertension, statins and dehydroepiandrosterone sulfate (DHEA S), is more effective than either agent alone, we induced pulmonary hypertension in adult male rats by exposing them to hypoxia (10%O2) for 3 weeks. We treated them with simvastatin (60 mg/l) and DHEA S (100 mg/l) in drinking water, either alone or in combination. Both simvastatin and DHEA S reduced mPAP (froma mean±s.d. of 34.4±4.4 to 27.6±5.9 and 26.7±4.8 mmHg, respectively), yet their combination was not more effective (26.7±7.9 mmHg). Differences in the degree of oxidative stress (indicated by malondialdehydeplasma concentration),the rate of superoxide production (electron paramagnetic resonance), or blood nitric oxide levels (chemiluminescence) did not explain the lack of additivity of the effect of DHEA S and simvastatin on pulmonary hypertension. We propose that the main mechanism of both drugs on pulmonary hypertension could be their inhibitory effect on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, which could explain their lack of additivity.

The patterns of endocrine response to surgical stress during different types of anesthesia and surgery in man.

The authors studied 123 patients undergoing minor (varicectomy) or major (cholecystectomy) surgery under diethyl ether, halothane, enflurane or hydroxydione anesthesia. The goal was to investigate the effects of emotional tension, anesthesia and surgical trauma, as well as glucose load, on the patterns of endocrine response under standardized clinical settings. The endocrine response (growth hormone, cortisol, insulin) was not modified significantly by emotional stress and the anesthetics used. Only prolactin was unique in that its release was markedly stimulated by halothane anesthesia. Neither the anesthetic drugs nor both types of surgical injury led to a constant hyperglycaemic response. Minor surgery failed to stimulate secretion of the studied hormones. However, major surgery stimulated growth hormone and cortisol secretion irrespective of the anesthetic used. Insulin secretion following glucose load was enhanced disproportionately. It is concluded that growth hormone level during surgical stress is determined by the extent and severity of surgical trauma, while neither anesthesia nor emotional tension exert any pronounced stimulative effect on its release. The observed changes in blood glucose levels and the lack of a proportionate insulin secretion are due to the effect of anesthesia rather than to that of surgery.