Changes in the ratio of plasma to intersitiial fluid volume during long-term antihypertensive therapy

Based on determinations of plasma (T-1824)(PV) and extracellular fluid volumes (82Br- distribution space) (ECFV), the PV/IF ratio (IF=ECFV.PV) was calculated three times with a 1-week interval between determinations in untreated patients with essential hypertension. During treatment with hydrochlorothiazide (13 males and 8 females), hydrochlorothiazide-triamterne (5 males and 5 females), hydrochlorothiazide-alpha-methyldopa (7 males and 4 females), and propranolol (6 males and 4 females), PV/IF was determined after 2 to 6 months of treatment. PV/IF was significantly reduced during hydrochlorothiazide treatment (delta PV/IF:--0.011, S.D.: 0.011, p is less than 0.001) and propranolol treatment (delta PV/IF:--0.017, S.D.: 0.022, p is less than 0.05), remained unchanged during hydrochlorothiazide-triamterene treatment and increased significantly during hydrochlorothiazide-alpha-methyldopa treatment (deltaPV/IF: .013, S.D.: 0.015, p is less than 0.05). There was a negative correlation between PV/IF and mean blood pressure during hydrochlorothiazide treatment (r:--0.49, n: 21, p is less than 0.05 (and hydrochlorothiazide-triamterene treatment (r:--0.79, n: 10, p is less than 0.01), whereas no correlation was found during treatment with hydrochlorothiazide-alpha-methyldopa or propranolol. Correlation between mean blood pressure and the individual volumes was not observed nor was there any correlation between changes in the parameters investigated. It is concluded that PV/IF is more accurately correlated to mean blood pressure than are the individual volumes and that, during long-term antihypertensive treatment, PV/IF will reflect changes in the tone of the capacitance vessels and the venous resistance vessels, resulting in a changed equilibrium between the intravascular and the interstitial volumes. It is suggested that the reduction in PV/IF during thiazide and propranolol therapy is related to a relative increase in venoconstrictor sympathetic activity whereas the increase in PV/IF by alpha-methyldopa is caused by decreased sympathetic tone and venodilation.