Preedy V R, Garlick P J
Clinical Nutrition and Metabolism Unit, Hospital for Tropical Diseases, London, UK.
J Pharm Pharmacol. 1988 Apr;40(4):267-71. doi: 10.1111/j.2042-7158.1988.tb05241.x.
The direct actions of the vasodilators, papaverine and phentolamine, on skeletal muscle metabolism were investigated in an isolated perfusion system. Eviscerated male rats were hemisected above the diaphragm and perfused, via the aorta, with a physiological perfusion medium containing erythrocytes. Papaverine, but not phentolamine, reduced vascular resistance throughout the 80 min study. Papaverine caused marked reductions in muscle concentrations of ATP and phosphocreatine, when compared with muscle from preparations without added vasodilators. This was accompanied by elevations in lactate concentrations. Water content of papaverine-treated muscle was also higher than values in unperfused muscle taken in-vivo. Phentolamine, in contrast, had no effect on muscle ATP, phosphocreatine, lactate or water content. The metabolism of the entire preparation was also investigated. Papaverine induced increases in lactate output while phentolamine treatment caused an initial uptake, followed by an increased output of lactate. There was no significant effect of either papaverine or phentolamine on the metabolism of K+ and glucose. Arteriovenous differences in oxygen-saturation of haemoglobin and pH were also unaltered. Investigations on aspects of protein metabolism demonstrated that papaverine and phentolamine caused significant reductions in muscle protein synthesis when compared with control perfusions or in-vivo values. The reductions in synthesis were not due to reductions in cAMP or limitations in branched-chain amino acid supply. However, there was the suggestion that phentolamine caused a decrease in protein breakdown. The overall data indicated that papaverine and phentolamine may cause impairment of skeletal muscle metabolism. This has important implications for their therapeutic or experimental use.
在一个离体灌注系统中研究了血管舒张剂罂粟碱和酚妥拉明对骨骼肌代谢的直接作用。将去内脏的雄性大鼠在横膈膜上方切成两半，并通过主动脉用含有红细胞的生理灌注介质进行灌注。在整个80分钟的研究中，罂粟碱降低了血管阻力，而酚妥拉明则没有。与未添加血管舒张剂的制剂的肌肉相比，罂粟碱使肌肉中的三磷酸腺苷（ATP）和磷酸肌酸浓度显著降低。这伴随着乳酸浓度的升高。用罂粟碱处理的肌肉的含水量也高于体内采集的未灌注肌肉的值。相比之下，酚妥拉明对肌肉中的ATP、磷酸肌酸、乳酸或含水量没有影响。还研究了整个制剂的代谢情况。罂粟碱使乳酸输出增加，而酚妥拉明处理则导致最初的摄取，随后乳酸输出增加。罂粟碱和酚妥拉明对钾离子和葡萄糖的代谢均无显著影响。血红蛋白氧饱和度和pH值的动静脉差异也未改变。对蛋白质代谢方面的研究表明，与对照灌注或体内值相比，罂粟碱和酚妥拉明使肌肉蛋白质合成显著减少。合成的减少并非由于环磷酸腺苷（cAMP）的减少或支链氨基酸供应的限制。然而，有迹象表明酚妥拉明导致蛋白质分解减少。总体数据表明，罂粟碱和酚妥拉明可能会损害骨骼肌代谢。这对它们的治疗或实验用途具有重要意义。
