Parathyroid Hormone-Related Protein Inhibits Endothelin-1 Production

The effect of human parathyroid hormone-related protein, a powerful vasodilator, on endothelin-1 production in cultured bovine pulmonary arterial endothelial cells was studied. Treatment with parathyroid hormone-related protein(1-34) at concentrations of 10 to 10 mol/L for 24 hours caused dose-dependent suppression of the secretion of endothelin-1, with maximal suppression at 10 mol/L to 74% of the control value. This inhibitory effect was completely abolished by coincubation with 100 ng/mL pertussis toxin, an inhibitor of GTP binding protein. Furthermore, addition of N -monomethyl-L-arginine, an inhibitor of nitric oxide synthase, at 10 mol/L significantly blocked the suppressive effect of parathyroid hormone-related protein(1-34) on endothelin-1 secretion, and further addition of 5 x 10 mol/L L-arginine significantly attenuated the blocking effect of N -monomethyl-L-arginine. Parathyroid hormone-related protein(1-34) at 10 mol/L resulted in an approximately fivefold increase in intracellular cGMP level. Northern blot analysis revealed that parathyroid hormone-related protein(1-34) inhibited both basal and thrombin-induced endothelin-1 gene expression. These findings suggest that the vasodilating property of parathyroid hormone-related protein may be mediated in part through its inhibitory effect on endothelin-1 production, which is probably mediated through nitric oxide and cGMP in endothelial cells. Thus, a feedback regulatory mechanism may exist between parathyroid hormone-related protein and endothelin-1 in the vascular wall. (Hypertension. 1996;27[part 1]:360-363.)