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(Hypertension. 2001;37:1486.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Effect of Insulin and Angiotensin II on Cell Calcium in Human Skin Fibroblasts

Giulio Ceolotto; Roberto Valente; Elisabetta Baritono; Stefania Reato; Elisabetta Iori; Alessandra Monari; Roberto Trevisan; Andrea Semplicini

From the Department of Clinical and Experimental Medicine, University of Padova Medical School, Padova, Italy.

Correspondence to Prof Andrea Semplicini, Clinica Medica IV–Policlinico Universitario, via Giustiniani 2–35128 Padova, Italy. E-mail asempl{at}ux1.unipd.it

Abstract—We have recently shown that insulin attenuates angiotensin II–induced intracellular Ca²⁺ mobilization in human skin fibroblasts from normotensive subjects. This study was designed to investigate the effects of angiotensin II and the interactions between insulin and angiotensin II on intracellular Ca²⁺ mobilization in skin fibroblasts from patients with essential hypertension. Fibroblasts were obtained from 9 normotensives and 18 hypertensives. Spectrofluorophotometric free Ca²⁺ measurement was performed in monolayers of 24-hour serum-deprived cells. Resting intracellular Ca²⁺ level and angiotensin II–stimulated intracellular Ca²⁺ peak were higher in fibroblasts from hypertensives compared with those from normotensives. The effect of acute insulin exposure was evaluated in fibroblasts from hypertensives subdivided on the basis of insulin sensitivity. In insulin-sensitive hypertensives, insulin significantly blunted the effects of angiotensin II on intracellular Ca²⁺ response, whereas in insulin-resistant patients, insulin did not modify intracellular Ca²⁺ response to angiotensin II. Pertussis toxin, a G_i-inhibitor, reduced angiotensin II–stimulated Ca²⁺ peak in insulin-sensitive but not in insulin-resistant hypertensives. In conclusion, the effects of angiotensin II on intracellular Ca²⁺ mobilization are more pronounced in fibroblasts from hypertensives compared with those from normotensives, and the inhibitory effect of insulin is blunted in insulin-resistant hypertensives by a G_i pertussis toxin–sensitive abnormality.

Key Words: angiotensin II • calcium • fibroblasts • G proteins • insulin • insulin resistance

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