Müller F B, Bolli P, Erne P, Kiowski W, Bühler F R
Am J Med. 1984 Aug 31;77(2B):11-5. doi: 10.1016/s0002-9343(84)80079-0.
A wide variety of drug treatments are available for the management of hypertension. Often, effective therapy is found only through a process of elimination. A more pathophysiologically oriented method of choosing therapy is based on classification of patients into those with low-, normal-, and high-renin hypertension. In the past, for example, diuretics were considered to be the most effective agents for the treatment of low-renin hypertension. Most cases of essential hypertension are characterized by increased vascular resistance. Calcium channel influx is a major determinant of the free intracellular calcium concentration that finally triggers the contractile process of the vascular smooth muscle cell and thereby determines arterial resistance. In man, free calcium concentration in platelets is closely related to the height of systolic and diastolic blood pressure. Vasodilatation produced by the intra-arterial infusion of a calcium channel blocker into the forearm circulation is significantly greater in hypertensive patients than in normotensive subjects, threefold that observed with sodium nitroprusside, and fourfold that found with prazosin. In hypertensive patients, these effects are correlated directly with plasma epinephrine--reflecting sympathoadrenal activity--and inversely with the activity and reactivity of the renin-angiotensin system. In several clinical studies, the decrease in blood pressure following the administration of calcium channel entry blockers was directly correlated to the patient's age and pretreatment blood pressure, and indirectly to the pretreatment plasma renin activity. The effects of these agents are apparently also comparable to the over-all responses achievable with beta blockers and diuretics. In the future, calcium entry blockers may replace diuretics as first-line therapy for older patients and those with low-renin hypertension.
有各种各样的药物治疗方法可用于管理高血压。通常,只有通过排除过程才能找到有效的治疗方法。一种更基于病理生理学的选择治疗方法是将患者分为低肾素、正常肾素和高肾素高血压患者。例如,过去利尿剂被认为是治疗低肾素高血压最有效的药物。大多数原发性高血压病例的特征是血管阻力增加。钙通道内流是细胞内游离钙浓度的主要决定因素,最终触发血管平滑肌细胞的收缩过程,从而决定动脉阻力。在人类中,血小板中的游离钙浓度与收缩压和舒张压的高度密切相关。将钙通道阻滞剂动脉内注入前臂循环所产生的血管舒张在高血压患者中比在正常血压受试者中明显更大,是硝普钠观察到的三倍,是哌唑嗪的四倍。在高血压患者中,这些作用与血浆肾上腺素直接相关——反映交感肾上腺活动——与肾素-血管紧张素系统的活性和反应性呈负相关。在几项临床研究中,给予钙通道阻滞剂后血压的降低与患者年龄和治疗前血压直接相关,与治疗前血浆肾素活性间接相关。这些药物的作用显然也与β受体阻滞剂和利尿剂所能达到的总体反应相当。未来,钙通道阻滞剂可能会取代利尿剂,成为老年患者和低肾素高血压患者的一线治疗药物。