Jacob S, Rett K, Henriksen E J
Department of Endocrinology, IV Medical Clinic, Eberhard-Karls-University, Tübingen, Germany.
Am J Hypertens. 1998 Oct;11(10):1258-65. doi: 10.1016/s0895-7061(98)00141-1.
Essential hypertension is, at least in many subjects, associated with a decrease in insulin sensitivity, whereas glycemic control is (still) normal. Metaanalyses of hypertension intervention studies revealed different efficacy of treatment on cerebral (cerebrovascular accidents [CVA]) and cardiac (coronary heart disease [CHD]) morbidity and mortality. Although CVA were reduced to an extent similar to that anticipated, the decrease in CHD was less than expected. These differences are likely to be caused by the different impact of concomitant cardiovascular risk factors, such as dyslipidemia, impaired glucose tolerance, and non-insulin-dependent diabetes mellitus on CHD and CVA. Frequently these cardiovascular risk factors are ineffectively controlled in hypertensive patients, and moreover, some of the widely used antihypertensive agents have unfavorable side effects and further deteriorate these particular metabolic risk factors. Therefore, the metabolic side effects of antihypertensive treatment have received more attention. During the past few years, studies demonstrated that most antihypertensive agents modify insulin sensitivity in parallel with alterations in the atherogenic lipid profile. Alpha1-blockers and angiotensin converting enzyme inhibitors were shown to either have no impact on or even improve insulin resistance and the profile of atherogenic lipids, whereas most of the calcium channel blockers were found to be metabolically inert. The diuretics and beta-adrenoreceptor antagonists further decrease insulin sensitivity and worsen dyslipidemia. The mechanisms by which beta-adrenoreceptor antagonist treatment exert its disadvantageous effects are not fully understood, but several possibilities exist: significant body weight gain, reduction in enzyme activities (muscle lipoprotein lipase and lecithin cholesterol acyltransferase), alterations in insulin clearance and insulin secretion, and, probably most important, reduced peripheral blood flow due to increase in total peripheral vascular resistance. Recent metabolic studies found beneficial effects of the newer vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. In many hypertensive patients, elevated sympathetic nerve activity and insulin resistance are a deleterious combination. Although conventional beta-blocker treatment was able to take care of the former, the latter got worse; the newer vasodilating beta-blocker generation seems to be capable of successfully treating both of them.
至少在许多患者中，原发性高血压与胰岛素敏感性降低相关，而血糖控制（仍然）正常。高血压干预研究的荟萃分析显示，治疗对脑（脑血管意外[CVA]）和心脏（冠心病[CHD]）发病率及死亡率有不同疗效。虽然CVA的降低程度与预期相似，但CHD的降低低于预期。这些差异可能是由伴随的心血管危险因素，如血脂异常、糖耐量受损和非胰岛素依赖型糖尿病对CHD和CVA的不同影响所致。在高血压患者中，这些心血管危险因素常常未得到有效控制，此外，一些广泛使用的抗高血压药物有不良副作用，会进一步恶化这些特定的代谢危险因素。因此，抗高血压治疗的代谢副作用受到了更多关注。在过去几年中，研究表明大多数抗高血压药物在改变致动脉粥样硬化血脂谱的同时也会改变胰岛素敏感性。α1阻滞剂和血管紧张素转换酶抑制剂对胰岛素抵抗和致动脉粥样硬化血脂谱无影响甚至有改善作用，而大多数钙通道阻滞剂在代谢方面无活性。利尿剂和β肾上腺素能受体拮抗剂会进一步降低胰岛素敏感性并使血脂异常恶化。β肾上腺素能受体拮抗剂治疗产生不利影响的机制尚未完全明确，但存在几种可能性：体重显著增加、酶活性（肌肉脂蛋白脂肪酶和卵磷脂胆固醇酰基转移酶）降低、胰岛素清除和胰岛素分泌改变，可能最重要的是由于总外周血管阻力增加导致外周血流减少。最近的代谢研究发现，新型血管舒张性β阻滞剂，如地来洛尔、卡维地洛和塞利洛尔，对胰岛素敏感性和致动脉粥样硬化危险因素有有益作用。在许多高血压患者中，交感神经活性升高和胰岛素抵抗是一种有害组合。虽然传统β阻滞剂治疗能够处理前者，但后者却恶化了；新型血管舒张性β阻滞剂似乎能够成功治疗这两者。
