Modern
antihypertensive therapy is enriched by an explosion in
drug development that makes available increasingly specific agents whose effects have advanced our understanding of pressor mechanisms. This and other research into hypertensive mechanisms has defined the clinical, pharmacological, and endocrinologic heterogeneity of human
hypertension. The sum of these developments is a greatly enhanced ability to identify curable and definable causes of
hypertension and to pathophysiologically stratify the remaining cases of
essential hypertension. Modern treatment can be much more specific than before. When long-term
drug therapy is indicated, the regimen is more likely to achieve a primary goal for each patient, that is, the fewest possible drugs in the smallest amount and in lowest frequency. Two clinically quantifiable mechanisms for long-term arteriolar vasoconstriction can be identified within the spectrum of human
hypertension. The first,
renin-mediated vasoconstriction, is directly related to the plasma
renin level. The second,
sodium-volume-related vasoconstriction, is marked by a reciprocally subnormal
renin level and involves abnormal
sodium retention and
calcium transport. A baseline
renin-
sodium profile can identify the pressure of one of these two forms of vasoconstriction and therefore is the key for the diagnosis of the two curable disorders that fully express one of the two pressor mechanisms--
renovascular hypertension and primary
aldosteronism.
Renovascular hypertension, more common than once thought, is often cured by angioplasty. It is important to diagnose these curable forms before beginning long-term
drug therapy. The
renin-
sodium profile, used in conjunction with serum
potassium and
creatinine measurements, is valuable not only in screening patients for curable forms, but also for stratifying the remainder according to the pathophysiological
vasoconstrictor mechanism that underlies the
hypertension. Converting
enzyme inhibitors or beta-blockers are, by themselves, often effective in correcting the
hypertension of high- or medium-
renin patients, whereas
calcium antagonists,
diuretic agents, or alpha-blockers alone are most effective against the low-
renin form of vasoconstriction. In the large midzone of
renin values, if monotherapy fails, a rational basis for combined antirenin-antisodium volume
therapies can be developed.