Inhibition by atrial natriuretic peptide of endothelin-1-stimulated proliferation of vascular smooth-muscle cells.

The effect of endothelin-1 (ET-1) on proliferation of aortic vascular smooth-muscle cells (VSMCs) from spontaneously hypertensive (SHRs) and normotensive Wistar-Kyoto (WKY) rats was assessed by the measurement of [3H]-thymidine incorporation into DNA. ET-1 stimulated DNA synthesis in a concentration-dependent manner. Half-maximal stimulation occurred at a concentration of 7 x 10(-11) M. Three separate administrations of ET-1 to the cell cultures resulted in a half-maximal stimulation at 3 x 10(-12) M in of VSCMs from SHRs. VSMCs from SHRs responded to a far greater extent compared with WKY rats. The stimulatory effect of ET-1 was significantly attenuated by atrial natriuretic peptide (ANP). Repeated administration of ANP led to exacerbation of the inhibitory effect. Serum-stimulated DNA synthesis was not influenced by ANP. The proliferative action of ET-1 and the inhibition by ANP are discussed with respect to the development of vascular disease in atherosclerosis and hypertension.