Relationship between cardiovascular haemodynamics and goals of antihypertensive therapy.

Hypertension is a haemodynamic disorder, reflecting a disturbance in the ratio between cardiac output and total peripheral resistance. In nearly all forms of established hypertension, total peripheral resistance is increased and cardiac output is abnormally low, particularly during exercise. When left untreated, total peripheral resistance increases, cardiac output falls and BP increases over time. The coronary reserve is reduced. Antihypertensive agents affect central haemodynamics differently. Vasodilators like alpha-blockers, calcium channel blockers and angiotensin-converting enzyme inhibitors all reduce total peripheral resistance and maintain cardiac output unchanged at rest as well as during exercise. In contrast, beta-blockers do not usually reduce total peripheral resistance much below the pretreatment level, and cardiac output is chronically depressed, particularly during exercise. However, the beta-blockers greatly reduce the workload in the heart by decreasing the rate-pressure product. Recently-developed beta-blockers with vasodilating activity, such as carvedilol, are based on a combination of beta-blockade and vasodilatation. Such beta-blockers also induce marked reduction in pressure-rate product and some reduction in total peripheral resistance. They induce less reduction in cardiac output during exercise than ordinary beta-blockers. From a theoretical point of view, this type of antihypertensive treatment should maintain good BP control, reduce cardiac workload and be associated with fewer side-effects than ordinary beta-blockers.