Therapies for perioperative hypertension: pharmacodynamic considerations

Cardiac output (CO) and peripheral resistance (PR), the two major determinants of systemic arterial blood pressure (BP), are regulated principally by the adrenergic (ADR) and renin–angiotensin–aldosterone (RAA) systems. Antihypertensive medications ultimately decrease CO, PR, or both, by acting at various sites in the ADR and RAA pathways or affecting cardiovascular functions directly. Beta–ADR–receptor blockers decrease heart rate (HR) and stroke volume (SV) by preventing the cardiostimulating effects of catecholamines and inhibiting renin release. Alpha–ADR–receptor blockers prevent the vasoconstricting effects of catecholamines and reduce PR (afterload). Angiotensin–converting enzyme inhibitors (ACEI) block the formation of angiotensin, a potent peripheral vasoconstrictor and aldosterone releaser. Hence, ACEI cause a decrease in both PR and CO, the latter by preventing salt and water retention by aldosterone, thereby reducing plasma volume and venous return. Direct vasorelaxation and, thus, a fall in PR can be achieved by vasodilators. These include drugs (e.g. calcium antagonists) that prevent the entry of calcium ions into vascular smooth muscle cells, and others (e.g. nitrovasodilators) that boost the intracellular levels of vasodilating second messengers (e.g. cyclic GMP). Antihypertensives from different classes are often combined to improve the ratio between therapeutic and adverseeffects.