Effect of insulin and angiotensin II on cell calcium in human skin fibroblasts

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 Giα-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 Giα pertussis toxin - sensitive abnormality.