Hemodynamic effects of bPTH(1-34) and its analogue Nle8,18Tyr34bPTH(3-34) amide.

We examined the vascular effects of bovine PTH(1-34) and of an analogue, Nle8,18Tyr34bPTH(3-34) amide, which inhibits adenylate cyclase activation by bPTH(1-34) in a number of in vitro systems. In the conscious dog. bPTH(1-34) injection produced dose-dependent hypotension associated with increased heart rate and cardiac output. The (3-34) analogue had no hypotensive effect in doses up to 6.0 micrograms/kg (1.5 nM/kg). In vitro studies revealed that bPTH(1-34) relaxed pitressin-contracted helical strips from the rat caudal artery. The (3-34) analogue displayed a weak, but definite inhibitory effect against the vasorelaxant effects of bPTH(1-34) with a pA2 of 5.5. The results further characterize the previously established hypotensive and vasorelaxant actions of bPTH(1-34), and suggest that the (3-34) analogue, which inhibits adenylate cyclase generation by bPTH(1-34) in nonvascular tissues, antagonizes the vasorelaxant effects of bPTH(1-34) as well. The results provide suggestive evidence that the vasorelaxant effects of bPTH(1-34) may be mediated by adenylate cyclase.