A new approach to the identification of pathogenetic factors and to therapy in human primary hypertension.

In experimental studies on renovascular hypertension, we found that the amplifier properties of the hypertrophied heart and resistance vessels contributed considerably more to the maintenance of the elevated blood pressure (BP) during the chronic phase of the disorder than the basic underlying cause. This must also occur in chronic primary hypertension. Accordingly, we hypothesized that after reversal of hypertrophy by antihypertensive medication, the cause(s) of hypertension should be easier to detect during the redevelopment of hypertension once medication was stopped than in the chronic phase of the disorder. We have studied three groups of patients with moderate/severe hypertension in whom BP was controlled for 1 month; 1 year; 15 months to 5 years. The rate of subsequent redevelopment of hypertension between the series was inversely related to the duration of therapy, which was mostly with beta blockers and diuretics. The differences in the rate of redevelopment of hypertension between series 2 and 3 suggest that, with the drugs used, reversal of vascular hypertrophy is quicker than reversal of left ventricular hypertrophy (LVH). In series 3, we observed an inverse relationship between LV mass and duration of therapy. Redevelopment of hypertension was slowest after obtaining regression of both vascular hypertrophy and LVH. Preliminary findings suggest that sympathetic overactivity is present during the redevelopment phase in the majority of patients. Our findings have suggested a new therapeutic strategy, where the effectiveness of nonpharmacological methods of controlling BP is enhanced by first causing regression of cardiovascular hypertrophy by drug treatment followed by a non-drug phase of maintaining normal BP. We have found moderate regular exercise one of the most effective nonpharmacological antihypertensive methods and have now maintained five patients with moderate hypertension at normal BP for 1 year, following an initial period of drug treatment.