Central Role of Sodium in Hypertension in Diabetic Subjects

Abstract

The common association between diabetes mellitus and hypertension may be promoted by several mechanisms. Patients with insulin-dependent (type I) diabetes and prone to develop nephropathy often have a familial predisposition for essential hypertension, whereas normotensive healthy offspring of nondiabetic essential hypertensive parents tend to have a reduced insulin sensitivity and increased plasma insulin levels. Na⁺ retention occurs as a characteristic alteration in type I or non-insulin-dependent (type II) diabetes; exchangeable body Na⁺ (Naex) is increased by 10% on average. This abnormality develops in the uncomplicated stage of diabetes and differentiates diabetic from nondiabetic essential hypertensive subjects. Possible Na(+)- retaining mechanisms include increased glomerular filtration of glucose leading to enhanced proximal tubular Na(+)-glucose cotransport, hyperinsulinemia (which activates several tubular Na⁺ transporters), an extravascular shift of fluid with Na⁺, and, once it occurs, renal failure. The pathogenetic role of Na⁺ retention in diabetes-associated hypertension is supported by positive correlations between systolic or mean blood pressure and Naex and by normalization of blood pressure after removal of excess Na⁺ by diuretic treatment in hypertensive diabetic subjects. The latter may also have an enhanced sensitivity of blood pressure to Na⁺. Plasma levels of active renin, angiotensin II, aldosterone, and catecholamines are usually normal or low in metabolically stable type I or type II diabetes. However, an exaggerated vascular reactivity to norepinephrine and angiotensin II commonly occurs already at uncomplicated stages of type I or type II diabetes. This may be a manifestation of functional (i.e., intracellular electrolytes) and/or morphological (proliferation, narrowing, and stiffening) vasculopathy. Diabetes-associated Na⁺ retention, vasculopathy, and a presumably inherited predisposition for both diabetes and essential hypertension may represent important complementary factors favoring the frequent occurrence of hypertension in the diabetic population.