Endothelin receptor A and p66Shc regulate spontaneous Ca2+oscillations in smooth muscle cells controlling renal arterial spontaneous motion

What is it about?

A wild variety of kidney diseases (hypertension induced nephropathy, diabetic nephropathy and others) are accompanied with a loss of ability of renal microvessels to regulate renal blood flow, which causes kidney damage. The ability of renal microvessels to maintain steady capillary pressure is regulated by factors acting through receptors of smooth muscle cells of blood vessels. Here, the effective sensitivity of two-photon excitation microscopy allowed for the first time to study Ca2+ oscillations in smooth muscle cells (SMC) embedded in the wall of small renal blood vessels. It is shown that Ca2+ spontaneous oscillations in smooth muscle cells are mediated by biologically active peptide termed endothelin-1 (ET-1) which is released from layer of endothelial cells. Spontaneous oscillations of intracellular calcium concentrations are directly linked to spontaneous motion of renal arteries, the process important for oxygen delivery to neighboring tissues. Remarkably, expression of adaptor protein termed p66Shc was shown to be a potent regulator of the amplitude of spontaneous Ca2+ oscillations in SMC of blood vessels and renal arterial spontaneous motion. Taken together these data suggest previously unknown role of p66Shc-controlled spontaneous Ca2+ oscillations in regulation of renal arterial spontaneous motion. Considering, that p66Shc is causing lack of function of renal arterioles leading to renal damage, efforts to come up with efficient inhibitors of p66Shc signaling and clinical studies evaluating the effect of such inhibitors seem to be warranted.

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