Cell density modulates the decrease of cytosolic free Ca2+ induced by atrial natriuretic hormone, S-nitroso-N-acetylpenicillamine and 8-bromo cyclic GMP in cultured rat mesangial cells.

Cyclic GMP-elevating agents, including atrial natriuretic hormone and NO-generating vasodilators, decrease cytosolic free Ca2+ levels in mesangial cells. We have investigated the role of cell density as a modulator of the decrease in cytosolic free Ca2+ induced by the cyclic GMP (cGMP)-elevating vasodilators atrial natriuretic peptide (99-126) [ANP (99-126); 'atriopeptin 28'] and the NO-generating vasodilator S-nitroso-N-acetylpenicillamine (SNAP), in cultured rat mesangial cells. Increasing cell density was significantly correlated with the decrease in cytosolic free Ca2+ induced by ANP (99-126) or SNAP. Moreover, this effect was independent of the cells' proliferative status. ANP (99-126) and SNAP induced greater fold stimulation of cGMP accumulation in high-density cells, but the levels of cGMP elicited by high concentrations of ANP (99-126) or SNAP were similar in high- and low-density cells. 8-Bromo cGMP was more effective in decreasing cytosolic free Ca2+ in high- than in low-density cells, suggesting that the greater effectiveness of ANP (99-126) and SNAP was, in part, due to greater effectiveness of endogenous cGMP in high-density cells. The results document that cell density, but not proliferative status, plays an important role in the modulation of intracellular Ca2+ dynamics in rat mesangial cells by atriopeptins, NO-generating vasodilators and cGMP.