Renin system activity as a determinant of response to treatment in hypertension and heart failure

In hypertension, irrespective of its underlying etiology, the baseline pretreatment renin-sodium profile predicts the antihypertensive action or the lack of it for five major types of antihypertensive drugs: 1) diuretic agents; 2) beta-receptor blockers; 3) converting-enzyme inhibitors; 4) the alpha 1 postsynaptic blocker, prazosin; and 5) the calcium channel blockers, verapamil and nifedipine. Moreover, vigorous compensatory activation of the renin-angiotensin system in response to therapy often explains initial drug ineffectiveness or resistance to treatment by diuretics and nonspecific vasodilators. This correlation between renin system behavior and antihypertensive drug efficacy likely reflect basic pharmacologic-physiologic interactions. This correlation is also observed in congestive heart failure without hypertension, where operant renin-aldosterone profiles may help to explain both drug efficacy and drug resistance to commonly administered therapeutic agents. Accordingly, a control system analysis of the renin axis has broad applications in therapy. The analysis is also conceptually significant since it exposes the operation of fundamentally different mechanisms of increased vascular resistance to flow occurring in different patients with hypertension or heart failure. One form is renin-angiotensin-mediated whereas the other, in the absence of renin, is associated with sodium-volume excess and/or abnormal alpha-adrenergic and calcium channel activity. Further definition of these two mechanisms of increased peripheral resistance could lead to a better understanding of the pathogenesis of some forms of essential hypertension and congestive heart failure.