Comparison of Hypotensive Response following Intravenous Injection of Parathyroid Hormone 1-84 and 1-34 in Conscious Rats |
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Authors: | K R Scott J Fox |
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Institution: | (1) NPS Pharmaceuticals, 383 Colorow Drive, Salt Lake City, UT 84108, USA |
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Abstract: | Activation of parathyroid hormone 1 (PTH-1) receptors on vascular smooth muscle cells causes relaxation and decreases blood
pressure in rats and humans. However, when PTH(1-84) and PTH(1-34) were injected in anesthetized rats, PTH(1-34) produced
a greater decrease in blood pressure. This study quantified the dose-response relationship of the hypotensive response to
intravenously injected PTH(1-84) and PTH(1-34) in conscious rats and assessed the role that the C-terminal region of PTH(1-84)
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 time-dependent. PTH(1-34) produced a greater
hypotensive effect than PTH(1-84) at most doses tested and was significantly different from PTH(1-84) at 1–10 nmol/kg. The
greatest difference in MAP decrease between PTH(1-84) and PTH(1-34) (24 and 35 mm Hg, respectively) occurred at 10 nmol/kg.
Median effective dose (ED50) values for PTH(1–84) and PTH(1-34) were significantly different (5.9 and 1.3 nmol/kg, respectively). The C-terminal PTH
fragments PTH(7–84), PTH(39–84), and PTH(53–84) 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 PTH(1-84) or PTH(1-34) (1.4 nmol/kg). In
conclusion, PTH(1-84) is a less potent but, because it induced the same maximum response, not a less efficacious hypotensive
agent than PTH(1-34) when administered by bolus intravenous injection in conscious rats. We found no evidence to support the
concept that the C-terminal region of PTH is responsible for this difference in potency. |
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Keywords: | Parathyroid hormone 1-84 Parathyroid hormone 1-34 C-terminal parathyroid hormone fragment Blood pressure Rat |
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