The factors responsible for the frequent occurrence of
hypertension in patients with
primary hyperparathyroidism have not been elucidated. Suggested mediators have included
hypercalcemia,
renal insufficiency, and increased plasma
renin activity. However, experimental results have not been reported in any species that test the hypothesis that sustained
hypertension in this clinical syndrome is due to consequences of
parathyroid hormone (PTH) excess versus unrelated factors (e.g., primary hypersecretion of other
hormones, NaCl sensitivity, genetic factors). Moreover, no systematic evaluation of the
renin or adrenal cortical responses to chronic PTH excess has been reported in any species. Accordingly, the present studies assessed the effects of chronic (12 days) continuous intravenous b-(1-34) PTH infusion in normal human subjects (n = 4). PTH infusion resulted in persistent
hypercalcemia and
hypertension, reversible during a 4-8-day recovery period. Transient but significant increases in urinary
tetrahydroaldosterone excretion and plasma
cortisol concentration were observed as
hypercalcemia and
hypertension developed. No significant changes in plasma
potassium concentration or plasma
renin activity were observed, suggesting that
hypercalcemia-induced transient hypersecretion of
ACTH was responsible for both
cortisol and
aldosterone responses. The present results suggest that
hypertension associated with clinical
primary hyperparathyroidism results from either direct or indirect effects of PTH excess, per se, and requires neither the long-term consequences/complications of the clinical disorder (e.g., severe
nephrocalcinosis,
renal insufficiency) nor primary hypersecretion of additional
hormones. These results are consistent with the hypothesis that
hypercalcemia alone or in combination with at least permissive levels of PTH can generate short-term, but persistent (12 days)
hypertension in human subjects and thus may be the initiating mechanism for
hypertension in clinical
primary hyperparathyroidism.