Vasodilation of the rat mesenteric vasculature by parathyroid hormone.
The isolated, perfused rat mesenteric vascular bed was used as a sensitive model of resistance vessel dynamics to evaluate the vascular actions of parathyroid hormone (PTH). Periarterial sympathetic nerve stimulation (PNS) was carried out at 8 Hz, 2 msec in pulse duration (supramaximal voltage) for 30 sec. The pressor response to PNS was decreased in a dose-dependent fashion by synthetic bovine PTH(1-34). Reduction of the PNS response was greater than 30% at 30 nM PTH. The concentration of PTH required to produce a half-maximal (ED50) decrease in PNS-induced tone was 4 nM. The phosphodiesterase inhibitor, methylisobutylxanthine, at 300 nM did not alter the PNS response when given alone, but potentiated PTH action. Isoproterenol (1 microM) decreased the PNS response by only 20%. Propranolol (1 microM) inhibited the effect of isoproterenol on the PNS response, but not that of PTH. The inhibitory analog of PTH, bPTH(7-34), blocked PTH action completely only at 30- to 50-fold higher concentrations than that of PTH. PTH also decreased the pressor response to norepinephrine infusion, similar to the effects on PNS. Again, bPTH(7-34) blocked the actions of PTH on norepinephrine vasoconstriction. These findings indicate that PTH has greater efficacy and potency for reducing PNS pressor activity in the mesenteric vasculature than isoproterenol and demonstrate that PTH has significant vascular effects at nanomolar concentrations.
G A
GA
Nickols
M A
MA
Metz
W H
WH
Cline
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008643:Mesentery / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000097:blood / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*
D010281:Parathyroid Hormone; D000242:Cyclic AMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine