Sodium-volume factor, cardiovascular reactivity and hypotensive mechanism of diuretic therapy in mild hypertension associated with diabetes mellitus

Diabetes mellitus is often associated with excess body sodium and frequently accompanied by hypertension. Relationships among blood pressure and various regulatory factors were studied before and after six weeks of diuretic therapy with chlorthalidone, 100 mg/day, in 17 diabetic subjects (aged 32 to 75 years) with borderline to moderate hypertension. Following a four-week placebo phase, mean supine blood pressure was 165/93 ± 26/15 (±SD) mm Hg and exchangeable sodium was increased (49 ± 4 versus 45 ± 4 meq/kg lean body mass in 90 normal subjects; p < 0.01). Blood volume, and supine and upright plasma renin, aldosterone, norepinephrine, epinephrine or dopamine levels were comparable to normal values. Measurements in eight diabetic subjects revealed an increased cardiovascular reactivity, as evidenced by decreased (p < 0.001) pressor doses of norepinephrine (68 ± 42 versus 151 ± 52 ng/kg/min) or angiotensin II (3.9 ± 1.2 versus 10.3 ± 5.5 ng/kg/min). Chlorthalidone decreased blood volume by 11 per cent, lowered body sodium (by 9 per cent) and cardiovascular sensitivity to norepinephrine (by 48 per cent) or angiotensin II (by 60 per cent) towards normal and reduced blood pressure by 11 per cent to 145/82 ± 13/12 mm Hg (11 per cent). Plasma renin and aldosterone were markedly increased by chlorthalidone, whereas plasma and urinary catecholamine levels were not significantly altered. These findings suggest that hypertension in patients with diabetes mellitus may partly depend on increased body sodium and/or an exaggerated cardiovascular reactivity to norepinephrine and angiotensin II. The blood pressure-lowering effect of diuretic therapy may be due to removal of excess sodium and the restoration of norepinephrine pressor sensitivity towards normal without an equivalent increase in adrenergic nervous activity.