Vasoactive and proliferative effects of parathyroid hormone and parathyroid hormone-related peptide on human vascular smooth muscle

Background: Hyperparathyroidism is associated with an increased incidence of hypertension and cardiovascular disease. Experiments in rats suggest that this results from desensitization of the normally inhibitory effects of parathyroid hormone-related peptide (PTHrP) on vascular smooth muscle cells (VSMCs) by previous exposure to parathyroid hormone (PTH). Methods: Isometric tension in vitro was measured in segments of vessels obtained at neck surgery from six normotensive patients with hyperparathyroidism and 12 eucalcaemic controls undergoing thyroid surgery. Vessels were precontracted with noradrenaline to allow the vasodilatory effects of PTH and PTHrP to be observed. Human VSMCs were cultured in 0.5, 5 and 15 per cent serum with or without PTH (10(-11) to 10(-7) nmol l(-1)) and proliferation was assessed by cell counts after 14 days. Results: Vasodilatation of arterial segments produced by both PTH 20 nmol l(-1) and PTHrP 100 nmol l(-1) did not differ significantly between control and hyperparathyroidism groups (P>0.08, Mann-Whitney U test). Vasodilatation by PTHrP was not reduced by preincubation of vessels in vitro with PTH 50 nmol l(-1) for 1 h (P>0.36, Wilcoxon test). No effects of PTH on serum-induced proliferation of human VSMCs were observed. Conclusion: These data imply that homologous desensitization to PTHrP is not implicated in the pathogenesis of vascular disease in patients with hyperparathyroidism.