Interaction of PDGF and natriuretic peptides on mesangial cell proliferation and endothelin secretion

The present study examined the possible interaction of platelet-derived growth factor (PDGF) and atrial or brain natriuretic peptides (ANP and BNP, respectively) on cellular proliferation and secretion of endothelin-1 in cultured rat mesangial cells. PDGF increased cellular proliferation and endothelin-1 secretion. The protein kinase C (PKC) inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, staurosporine, and PKC inhibitor peptide, inhibited such stimulation. Rat ANP-(1-28) and rat BNP-45 exhibited clearly dose-related inhibition of PDGF-stimulated cellular proliferation and endothelin-1 secretion. This inhibition by ANP and BNP was paralleled by an increase in the cellular level of guanosine 3',5'-cyclic monophosphate (cGMP). Results indicate that PDGF stimulates cellular proliferation and endothelin-1 secretion in cultured rat mesangial cells by a mechanism probably involving activation of PKC and that ANP and BNP inhibit such stimulation through a cGMP-dependent process.