Hypertension in adult onset diabetes mellitus: abnormal renal hemodynamics and endogenous vasoregulatory factors

Abstract

We evaluated 10 adult onset diabetics who developed hypertension well after the onset of glucose intolerance. Systemic and renal hemodynamics, intravascular volume, the renin-angiotensin-aldosterone axis, and the renal kallikrein-kinin system were examined at extremes of sodium intake, and compared to results from matched normotensive and essential hypertensive subjects. On unrestricted sodium diet, the diabetics, compared to normotensives, had significantly decreased blood volume (p less than 0.01), and preservation of renal plasma and blood flow, but significantly elevated renal vascular resistance (p less than 0.05), decreased creatinine clearance (p less than 0.01), and decreased filtration fraction (p less than 0.01). On restricted sodium intake, diabetics, compared to normotensives, had reduced urinary kallikrein activity (p less than 0.01) and reduced ambulatory plasma renin activity (p less than 0.01). Essential hypertensives were similar to diabetics in that both had reduced intravascular volume, elevated renal vascular resistance, and reduced levels of stimulated urinary kallikrein and ambulatory renin activities, but plasma aldosterone concentrations were reduced in diabetics compared to both normotensives and essential hypertensives under all dietary conditions. The ratio urinary kallikrein activity/supine plasma renin activity in diabetics correlated with renal blood flow (p less than 0.05), and inversely with renal vascular resistance (p less than 0.05). We conclude that these hypertensive diabetics have multiple abnormalities in intrarenal hemodynamics that may be related, in part, to abnormal activities of the renal enzymes renin and kallikrein. The kallikrein defect may be an etiologic factor in their hypertension.