Daugirdas J T, Al-Kudsi R R, Ing T S, Yang M C, Leehey D J, Pang P K
Miner Electrolyte Metab. 1987;13(1):33-7.
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.
我们研究了牛甲状旁腺激素（1-34）[bPTH(1-34)]及其类似物Nle8,18Tyr34bPTH(3-34)酰胺的血管效应，该类似物在许多体外系统中可抑制bPTH(1-34)激活腺苷酸环化酶。在清醒犬中，注射bPTH(1-34)可产生剂量依赖性低血压，并伴有心率和心输出量增加。（3-34）类似物在剂量高达6.0微克/千克（1.5纳摩尔/千克）时无降压作用。体外研究显示，bPTH(1-34)可使大鼠尾动脉中由加压素收缩的螺旋条带舒张。（3-34）类似物对bPTH(1-34)的血管舒张作用表现出微弱但明确的抑制作用，其pA2为5.5。这些结果进一步明确了bPTH(1-34)先前已确定的降压和血管舒张作用，并表明在非血管组织中抑制bPTH(1-34)生成腺苷酸环化酶的（3-34）类似物也可拮抗bPTH(1-34)的血管舒张作用。这些结果提供了提示性证据，表明bPTH(1-34)的血管舒张作用可能由腺苷酸环化酶介导。
