Parathyroid hormone and the altered vascular response to norepinephrine in uremia

Patients with chronic renal failure manifest reduced pressor response to norepinephrine (NE); this abnormality is at least partly responsible for the autonomic nervous system dysfunction observed in these patients. Since uremia is associated with increased levels of parathyroid hormone (PTH) and since PTH blunts the pressor effect of NE most likely via activation of prostaglandins, we have studied the relationship between blood levels of PTH and the reduced pressor response to NE in 17 uremic patients and we examined the effect of treatment with indomethacin on the response to NE in 9 uremic and 5 normal subjects. There was a significant negative correlation (r = -0.63, p less than 0.01) between the changes in blood pressure and the blood levels of PTH in uremic patients. Treatment with indomethacin was followed by significant improvement or normalization of the pressor response to NE in uremic patients. These data are consistent with the notion that the decreased pressor response to NE in uremia is due to increased production of prostaglandins induced by excess PTH and provide a therapeutic tool for the treatment of some of the manifestations of autonomic nervous system dysfunction in uremia.