Department of Experimental Medicine and Immunotherapeutics, Vascular Research Clinic, ACCI Level 3, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Handb Exp Pharmacol. 2024;285:297-332. doi: 10.1007/164_2024_719.
Hypertension is a very prevalent condition associated with high mortality and morbidity, secondary to changes resulting in blood vessels and resultant end-organ damage. Haemodynamic changes, including an initial rise in cardiac output followed by an increase in total peripheral resistance, denote the early changes associated with borderline or stage 1 hypertension, especially in young men. Increased sodium reabsorption leading to kidney damage is another mechanism proposed as one of the initial triggers for essential hypertension. The underlying pathophysiological mechanisms include catecholamine-induced α- and ß-adrenoceptor stimulation, and renin-angiotensin-aldosterone system activation leading to endothelial dysfunction which is believed to lead to persistent blood pressure elevation.α blockers, α agonists, and ß blockers were among the first oral anti-hypertensives. They are no longer first-line therapy after outcome trials did not demonstrate any benefits over and above other agents, despite similar blood pressure reductions. Angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), calcium channel blockers, and thiazide-like diuretics are now considered the first line of therapy, although adrenoceptor agents still have a role as second- or third-line therapy. The chapter also highlights hypertension in specific medical conditions such as pregnancy, phaeochromocytoma, hyperthyroidism, portal hypertension, pulmonary arterial hypertension, and ocular hypertension, to provide an overview for clinicians and researchers interested in the role of adrenoceptors in the pathophysiology and management of hypertension.
高血压是一种非常普遍的疾病,与高死亡率和高发病率相关,这是由于血管变化和由此导致的终末器官损伤所致。血流动力学变化,包括初始心输出量增加,随后总外周阻力增加,标志着与边缘或 1 期高血压相关的早期变化,尤其是在年轻男性中。钠重吸收增加导致肾脏损伤是另一种被认为是原发性高血压最初触发因素之一的机制。潜在的病理生理机制包括儿茶酚胺诱导的α和β肾上腺素能受体刺激,以及肾素-血管紧张素-醛固酮系统激活导致内皮功能障碍,据信这会导致持续的血压升高。α受体阻滞剂、α激动剂和β受体阻滞剂是最早的口服抗高血压药物之一。尽管血压降低相似,但结果试验并未证明它们比其他药物更有优势,因此它们不再是一线治疗药物。血管紧张素转换酶抑制剂(或血管紧张素受体阻滞剂)、钙通道阻滞剂和噻嗪类利尿剂现在被认为是一线治疗药物,尽管肾上腺素能受体药物仍然在二线或三线治疗中发挥作用。本章还强调了特定医疗条件下的高血压,如妊娠、嗜铬细胞瘤、甲状腺功能亢进、门静脉高压、肺动脉高压和眼内压升高,为对肾上腺素能受体在高血压病理生理学和管理中的作用感兴趣的临床医生和研究人员提供了概述。