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 mumol/L) and bradykinin (1 mumol/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.
Duner
E
E
Istituto di Medicina Interna, National Research Council (CNR) Center for the Study of Aging, Università di Padova, Italy.
Di Virgilio
F
F
Trevisan
R
R
Cipollina
M R
MR
Crepaldi
G
G
Nosadini
R
R
D000368:Aged; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D001706:Biopsy; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012867:Skin / Q000166:cytology / Q000378:metabolism*
D000804:Angiotensin II; D001920:Bradykinin; D002118:Calcium