Comparison of hypotensive response following intravenous injection of parathyroid hormone 1-84 and 1-34 in conscious rats.
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.
Scott
K R
KR
NPS Pharmaceuticals, 383 Colorow Drive, Salt Lake City, UT 84108, USA.
Fox
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology; D007275:Injections, Intravenous; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C023443:carboxyl-terminal parathyroid hormone