Authors: K R Scott J Fox
Publish Date: 2006/12/08
Volume: 79, Issue: 6, Pages: 389-394
Abstract
Activation of parathyroid hormone 1 PTH1 receptors on vascular smooth muscle cells causes relaxation and decreases blood pressure in rats and humans However when PTH184 and PTH134 were injected in anesthetized rats PTH134 produced a greater decrease in blood pressure This study quantified the doseresponse relationship of the hypotensive response to intravenously injected PTH184 and PTH134 in conscious rats and assessed the role that the Cterminal region of PTH184 played in the differences Mean arterial pressure MAP decreased rapidly following injection of both peptides 0–100 nmol/kg and reached a nadir at 1–2 minutes before increasing at a rate that was dose and timedependent PTH134 produced a greater hypotensive effect than PTH184 at most doses tested and was significantly different from PTH184 at 1–10 nmol/kg The greatest difference in MAP decrease between PTH184 and PTH134 24 and 35 mm Hg respectively occurred at 10 nmol/kg Median effective dose ED50 values for PTH1–84 and PTH134 were significantly different 59 and 13 nmol/kg respectively The Cterminal PTH fragments PTH7–84 PTH39–84 and PTH53–84 did not affect MAP when injected alone 10 nmol/kg nor did they influence the hypotensive response when given at a 10–fold molar excess in combination with PTH184 or PTH134 14 nmol/kg In conclusion PTH184 is a less potent but because it induced the same maximum response not a less efficacious hypotensive agent than PTH134 when administered by bolus intravenous injection in conscious rats We found no evidence to support the concept that the Cterminal region of PTH is responsible for this difference in potency
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