Crass M F, Moore P L, Strickland M L, Pang P K, Citak M S
Am J Physiol. 1985 Aug;249(2 Pt 1):E187-94. doi: 10.1152/ajpendo.1985.249.2.E187.
The synthetic amino terminal fragment of parathyroid hormone, PTH-(1-34), is a potent coronary artery vasodilator in the dog. In the present study, using instrumented open-chest dogs, we have performed the initial characterization of this effect and showed other dose-related cardiovascular effects of the hormone. A near-maximal flow response was obtained after intracoronary injection of 0.024 nmol X kg-1 PTH-(1-34) with minor, if any, concomitant changes in mean blood pressure, contractile force, or heart rate. At higher doses, mean blood pressure decreased while contractile force and heart rate increased in dose-dependent fashion. Infusion of PTH-(1-34) for 20 min showed that the vasodilatory effect could be sustained without a concomitant decrease in mean arterial pressure. Pharmacological characterization showed for the first time that the coronary response to PTH-(1-34) was unaltered in the presence of beta- or alpha-adrenergic, muscarinic, or histaminergic blockades. We conclude that PTH-(1-34), an endogenous circulating calcemic peptide, produces a large increase in coronary blood flow at doses sufficiently low to preclude complicating effects on blood pressure, contractile force, and heart rate. Furthermore, the results suggest that the vasodilatory effects may be specific.
甲状旁腺激素的合成氨基末端片段PTH-(1 - 34)是犬冠状动脉的强效血管扩张剂。在本研究中,我们使用仪器化的开胸犬对这种效应进行了初步表征,并展示了该激素其他与剂量相关的心血管效应。冠状动脉内注射0.024 nmol·kg-1的PTH-(1 - 34)后可获得接近最大的血流反应,平均血压、收缩力或心率即使有变化也很轻微。在更高剂量下,平均血压下降,而收缩力和心率呈剂量依赖性增加。输注PTH-(1 - 34) 20分钟表明,血管舒张作用可持续,且平均动脉压不会随之降低。药理学表征首次表明,在存在β或α肾上腺素能、毒蕈碱能或组胺能阻滞剂的情况下,冠状动脉对PTH-(1 - 34)的反应未改变。我们得出结论,PTH-(1 - 34)作为一种内源性循环的血钙调节肽,在剂量足够低以至于不会对血压、收缩力和心率产生复杂影响时,可使冠状动脉血流量大幅增加。此外,结果表明这种血管舒张作用可能具有特异性。