Subacute infusion of physiological doses of parathyroid hormone raises blood pressure in humans.
BACKGROUND
Acute administration of parathyroid hormone (PTH) causes vasodilation and blood pressure decrease in experimental animals. This effect contrasts with the putative role of secondary hyperparathyroidism in the pathogenesis of hypertension of patients with renal failure. Uraemia is characterized by insulin resistance and hyperinsulinaemia. We therefore investigated whether subacute administration of physiological doses of human 1,34-PTH affects blood pressure under conditions of controlled insulin levels (euglycaemic clamp technique) in humans.


METHODS
In a double-blind cross-over design 10 healthy male subjects received, on two occasions, in random order, for 2 h, either a sham infusion or an infusion of 200 units of 1,34-PTH.


RESULTS
Mean ionized calcium concentration increased significantly (P < 0.01) within the normal range during euglycaemic hyperinsulinaemia, both with sham infusion (from 1.25 +/- 0.04 to 1.29 +/- 0.02 mmol/l) and with infusion of 1,34-PTH, but the increase was more marked with 1,34-PTH administration (from 1.26 +/- 0.05 to 1.33 +/- 0.07). In addition, mean platelet intracellular calcium concentration (by fluorescence spectroscopy) was unchanged with sham infusion (49.9 +/- 4.1 versus 50.3 +/- 5.0 nmol), but increased significantly (P < 0.05; paired t-test) after 1,34-PTH infusion (from 49.8 +/- 5.0 to 52.8 +/- 5.8). The infusion of 1,34-PTH resulted in a significant (P < 0.01) increase in mean MAP (from 84 +/- 5 to 88 +/- 5 mmHg) as compared with sham infusion (85 +/- 4 versus 86 +/- 4). The intra-individual changes in intracellular calcium concentration (delta[Ca2+]i) were significantly correlated to the changes in mean MAP (delta MAP) (r = 0.87, P < 0.001). In contrast to blood pressure, insulin sensitivity was not affected by 1,34-PTH infusion (M-value: 7.2 +/- 1.6 mg/kg per min) as compared with sham infusion (7.3 +/- 1.4).


CONCLUSIONS
Subacute administration of physiological doses of parathyroid hormone under hyperinsulinaemic conditions significantly affects intracellular calcium and blood pressure in healthy subjects, but does not affect the action of insulin.
Fliser
D
D
Department of Internal Medicine, Ruperto-Carola University, Heidelberg, Germany.
Franek
E
E
Fode
P
P
Stefanski
A
A
Schmitt
C P
CP
Lyons
M
M
Ritz
E
E
D000328:Adult; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology*; D002118:Calcium / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D010281:Parathyroid Hormone / Q000502:physiology*; D019379:Teriparatide / Q000008:administration & dosage*
D001786:Blood Glucose; D007328:Insulin; D010281:Parathyroid Hormone; D019379:Teriparatide; D002118:Calcium