Calcimimetic NPS R-568 induces hypotensive effect in spontaneously hypertensive rats.
BACKGROUND
The discovery of calcium receptors and calcimimetics created the possibility of "pharmacologic parathyroidectomy" (phPTX), which decreased secretion of parathormone (PTH). Parathyroid glands of spontaneously hypertensive rats (SHR) and of patients with primary hyperparathyroidism and hypertension secrete parathyroid hypertensive factor (PHF). Parathyroidectomy decreases blood pressure in these rats and in patients. The present study determined whether phPTX induced by calcimimetics decreases mean arterial blood pressure (MAP) in hypertensive rats.


METHODS
Hypertensive SHR and normotensive Wistar Kyoto (WKY) rats were used. Clearance experiments were performed and the effect of 1 mg/kg body weight (given intravenously) synthesized NPS R-568 (NPS) on MAP in the presence or absence of thyroparathyroidectomy (TPTX) was monitored.


RESULTS
The success phPTX and TPTX were proven by a significant decrease in plasma Ca(2+) concentration and a decrease in urinary fractional phosphate excretion (FE Pi). The administration of NPS significantly decreased blood pressure in SHR versus SHR/control: Delta(0-50 min of experiment) MAP -16.5 +/- 2.5 mm Hg v -3.2 +/- 1.5 mm Hg (P < .002). The TPTX decreased blood pressure in SHR versus SHR/control and was not different versus SHR/TPTX/NPS (DeltaMAP: -10.2 +/- 1.6 mm Hg v -3.2 +/- 1.5 mm Hg (P < .01) and v -8.3 +/- 2.2 mm Hg (P = not significant). In normotensive WKY rats application of NPS did not reach significance in DeltaMAP: -6.7 +/- 1.8 mm Hg v -2.6 +/- 2.8 mm Hg (P = not significant) in WKY/control. The TPTX lowered blood pressure in WKY versus WKY/control and remained unchanged versus WKY/TPTX/NPS (DeltaMAP: -11.3 +/- 1.7 mm Hg v -2.6 +/- 2.8 mm Hg (P < .04) and v -11.4 +/- 2.6 mm Hg (P = not significant).


CONCLUSIONS
We conclude that phPTX with NPS R-568 is responsible for a decrease of MAP in SHR.
Rybczyńska
Apolonia
A
Laboratory of Pathophysiology, Medical University of Gdańsk, ul. Tuwuma 15, 80-210 Gdańsk, Poland. aryb@amg.gda.pl
Boblewski
Konrad
K
Lehmann
Artur
A
Orlewska
Czeslawa
C
Foks
Henryk
H
Drewnowska
Krystyna
K
Hoppe
Anzelm
A
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000819:agonists* / Q000378:metabolism; D006961:Hyperparathyroidism / Q000601:surgery; D006973:Hypertension / Q000188:drug therapy*; D007022:Hypotension / Q000139:chemically induced*; D008297:Male; D010280:Parathyroid Glands / Q000502:physiology*; D016105:Parathyroidectomy; D010627:Phenethylamines; D010710:Phosphates / Q000378:metabolism; D011437:Propylamines; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000814:Aniline Compounds; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010627:Phenethylamines; D010710:Phosphates; D011437:Propylamines; D002118:Calcium