Antihypertensive drugs and baroreceptor reflex control of heart rate and blood pressure.

The arterial baroreceptor reflex (BR; aortic and carotid sinus BR) and the cardiopulmonary BR are the most important reflexes acting as buffer systems for the maintenance of arterial pressure around a fixed physiologic value. They act as permanent inhibitory systems on the central cardiovascular structures and they can be either activated or deactivated by using selective techniques. During chronic hypertension there are structural alterations of the peripheral and/or central components of the BR that become "reset", with a shift in the function curve relating BR activity to blood pressure (BP) in the direction of higher pressure values. As a consequence of the hypertension-induced resetting phenomenon, both the threshold pressure and sensitivity of BR are disturbed. However, if BR resetting during hypertension clearly decreases the sensitivity of BR control of heart rate (HR), BR control of peripheral resistance and arterial pressure as a whole is preserved and even increased when hypertension develops. Thus, this apparent discrepancy between BR control of HR and BP during hypertension demonstrates that evaluation of an antihypertensive therapy on reflex control of HR alone cannot predict what will happen to BR control of the whole cardiovascular system. Regarding BR control of HR, in contrast to the classical arteriolar vasodilators such as hydralazine and its derivatives, the majority of the modern antihypertensive drugs do not evoke reflex tachycardia in response to lowering of BP in normotensive or hypertensive subjects. Although the intrinsic pharmacologic mechanisms of action of these drugs on BR may be quite different (e.g., alpha 1-or beta-adrenoreceptor blocking agents, converting enzyme inhibitors, certain calcium-channel blockers of the phenyldihydropyridine group, and so on), they all shift in a parallel manner the set-point of the BR response curve towards lower pressures, with no change in HR or R-R interval. Generally, this resetting phenomenon occurs after several weeks or months of antihypertensive therapy, but it can also occur acutely (e.g. after IV injection) after administration of drugs such as prazosin or ketanserin. Finally, antihypertensive agents such as clonidine and methyldopa can simultaneously reset the BR and increase its sensitivity, thus leading to almost complete restoration of control of HR response despite the concomitant decrease in BP. Regarding BR control of blood pressure, only captopril and especially celiprolol (a beta 1-adrenoreceptor blocking drug with vasodilating properties) are able to restore almost normal BR control of arterial pressure.