Intracellular free calcium abnormalities in fibroblasts from non-insulin-dependent diabetic patients with and without arterial hypertension

As arterial hypertension is frequently associated with diabetes, it is possible that altered intracellular free calcium ([Ca2+](i)) handling, as reported in non-insulin-dependent diabetic patients, is accounted for by abnormalities caused by hypertension rather than diabetes. Our aim was to investigate [Ca2+](i) transients triggered by two extracellular agonists, bradykinin and angiotensin II, with or without chronic insulin exposure, in cultured skin fibroblasts from 10 normotensive and 10 hypertensive non-insulin-dependent patients, matched for age, body mass index, and metabolic control, with fibroblasts from 10 healthy control subjects. Long-term cultured fibroblasts were loaded with fura 2-AM for measurement of [Ca2+](i). Resting [Ca2+](i) levels were similar in the three groups of subjects. [Ca2+](i) spikes stimulated by angiotensin II (0.1 mu mol/L) and bradykinin (1 mu mol/L) were significantly greater in hypertensive non-insulin-dependent diabetic patients (216 +/- 43 and 374 +/- 39 nmol/L, respectively) than in normotensive patients (174 +/- 16 and 267 +/- 55 nmol/L) and control subjects (188 +/- 29 and 320 +/- 78 nmol/L). Also, ionomycin evoked a greater [Ca2+](i) response in hypertensive than normotensive non-insulin-dependent diabetic patients and in control subjects. Chronic insulin exposure increased by 70% to 90% the [Ca2+](i) response to both angiotensin II and bradykinin in control subjects and normotensive non-insulin-dependent diabetic patients but not in hypertensive patients. The presence of abnormalities in [Ca2+](i) transients in fibroblasts from only hypertensive non-insulin-dependent diabetic patients supports the possibility that these defects are a feature of concomitant arterial hypertension rather than of diabetes or its disturbed metabolic milieu.