Long-Term Thiazide Therapy in Essential Hypertension

Plasma volume (RIHSA) and peripheral plasma renin activity (Pickens' method) were measured in eight essential hypertensive patients treated with thiazide diuretics alone for periods ranging from 6 to 24 months. Treatment was then stopped and measurements repeated at weekly intervals for a month. During the first week of discontinuance, body weight and plasma volume rose in all ( P < 0.001 for both), while peripheral plasma renin activity fell from 3.66 to 1.04 ng/ml ( P < 0.005), and serum sodium concentration was practically unchanged. Over the next 3 weeks, both plasma volume and body weight gradually fell from the high first week "rebound" values to plateau at levels higher than those obtained during treatment (2741 vs. 2567 ml, P < 0.001 and 76.1 vs. 74.7 kg, P < 0.001, respectively). At the same time, peripheral plasma renin activity remained stable and markedly lower than during treatment ( P < 0.001), while blood pressure gradually rose. Extracellular water (ECW) was measured serially (radiobromine) in five patients; in all, body weight variations were completely accounted for by changes in ECW, and ratio of plasma to interstitial fluid volume remained stable. These data indicate that blood pressure reduction by longterm thiazide therapy was associated with persistent plasma volume contraction and occurred despite increased peripheral renin activity. There was no evidence for chronic intracellular dehydration, and variations in peripheral renin activity were related to changes in plasma volume and not to serum sodium concentration.