Abstract
Adaptor protein p66Shc is overexpressed in smooth muscle cells of renal resistance vessels of hypertensive salt-sensitive rats and is involved in the regulation of renal vascular tone. We applied 2-photon laser scanning fluorescence microscopy to analyze spontaneous dynamic fluctuations in intracellular calcium concentrations ([Ca(2+)](i)) in smooth muscle cells embedded in the walls of freshly isolated renal resistance arteries. The amplitude, number of events, and frequency of spontaneous [Ca(2+)](i) oscillations triggered by endogenously released endothelin-1 were recorded in smooth muscle cells of the renal arteries. Endothelin receptor A antagonist BQ123 dramatically reduced the amplitude and frequency of spontaneous Ca(2+) events, producing marked inhibition of renal vessels spontaneous motion. Spontaneous Ca(2+) fluctuations in smooth muscle cells of p66Shc knockout (p66ShcKO) rats had significantly higher amplitude than in control rats. The frequency of spontaneous [Ca(2+)](i) oscillations did not change in p66ShcKO rats, suggesting that p66Shc expression did not affect endothelin-1 release from resident endothelial cells. Acute application of endothelin-1 revealed significantly elevated production of the total [Ca(2+)](i) in p66ShcKO rats. Spontaneous cytosolic Ca(2+) oscillations in smooth muscle cells of renal vessels mediate their spontaneous motion via the endothelin-1/endothelin receptor A pathway. p66Shc decreases the amplitude of individual changes in [Ca(2+)](i), which mitigates the spontaneous motion of renal vessels.-Palygin, O., Miller, B. S., Nishijima, Y., Zhang, D. X., Staruschenko, A., Sorokin, A. Endothelin receptor A and p66Shc regulate spontaneous Ca(2+) oscillations in smooth muscle cells controlling renal arterial spontaneous motion.