EFFECTS OF ANTIHYPERTENSIVE DRUG CLASSES ON REGRESSION OF CONNECTIVE-TISSUE COMPONENTS OF HYPERTENSION

Hypertension leads to structural and functional adaptations which, although initially protective for the cardiovascular system, ultimately work to sustain and reinforce the hypertensive state. Although blood pressure (BP) may be effectively lowered by a variety of treatments, it is becoming clear that these structural adaptations, and the risks and consequences of hypertension, may persist long after BP has been restored to normal levels. Cardiovascular tissues appear to be highly sensitive to increased BP, responding quickly with large and proportional increases in collagen and elastin. The sensitivity of this response to increase pressure, together with the slow turnover of these connective tissue proteins, suggests a mechanism by which transient or intermittent episodes of hypertension may lead to cumulative and persistent structural changes in cardiovascular tissues. With some exceptions, studies directly investigating the reversibility of these connective tissues changes have generally confirmed that increased cardiovascular collagen and elastin persist for long periods of time after BP lowering, independent of the treatment method used to achieve that lowering. Because maintenance of elevated levels of collagen and elastin is principally caused by the slow turnover of the proteins rather than by their continued production, rapid and effective reversal of cardiovascular connective tissue changes may require the development of pharmacological agents that promote or accelerate the turnover of these proteins.