Nishiwaki K, Nyhan D P, Stuart R S, Desai P M, Peterson W P, Rock P, Pribble C G, Murray P A
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287.
J Appl Physiol (1985). 1993 Feb;74(2):733-41. doi: 10.1152/jappl.1993.74.2.733.
We investigated the extent to which sympathetic alpha 1-adrenoreceptor activation is involved in chronic pulmonary vascular regulation in conscious dogs after left lung autotransplantation (LLA). Continuous left pulmonary vascular pressure-flow plots were generated in conscious dogs 3-4 wk post-LLA and in identically instrumented conscious dogs not subjected to LLA (sham-operated controls). LLA resulted in a marked upward shift in the baseline left pulmonary vascular pressure-flow relationship compared with the control group (P < 0.01), i.e., LLA caused a chronic increase in pulmonary vascular resistance. The sympathetic alpha 1-adrenoreceptor antagonist prazosin partially reversed (P < 0.01) the LLA-induced increase in pulmonary vascular resistance. Circulating concentrations of norepinephrine and epinephrine at 2 and 4 wk post-LLA were not significantly different from values measured in control dogs. However, the dose-response relationship to the exogenous administration of the sympathetic alpha 1-adrenoreceptor agonist phenylephrine was shifted (P < 0.05) to the left post-LLA compared with control, which indicates an increase in pulmonary vascular reactivity to alpha 1-adrenoreceptor activation. This effect was not due to a generalized increase in pulmonary vascular reactivity to vasoconstrictor stimuli because the dose-response relationship to the thromboxane analogue U-46619 was not significantly altered post-LLA compared with control. Thus LLA results in a chronic increase in pulmonary vascular resistance in conscious dogs. A component of the increase in pulmonary vascular resistance resulting from LLA is mediated by an enhanced reactivity to sympathetic alpha 1-adrenoreceptor activation.
我们研究了在左肺自体移植（LLA）后的清醒犬中，交感α1-肾上腺素能受体激活在慢性肺血管调节中的参与程度。在LLA术后3-4周的清醒犬以及未进行LLA的相同仪器装备的清醒犬（假手术对照组）中，生成连续的左肺血管压力-流量图。与对照组相比，LLA导致基线左肺血管压力-流量关系显著上移（P < 0.01），即LLA引起肺血管阻力慢性增加。交感α1-肾上腺素能受体拮抗剂哌唑嗪部分逆转了（P < 0.01）LLA诱导的肺血管阻力增加。LLA术后2周和4周时，去甲肾上腺素和肾上腺素的循环浓度与在对照犬中测得的值无显著差异。然而，与对照相比，LLA术后对外源性给予交感α1-肾上腺素能受体激动剂去氧肾上腺素的剂量-反应关系向左移位（P < 0.05），这表明肺血管对α1-肾上腺素能受体激活的反应性增加。这种效应并非由于肺血管对血管收缩刺激的反应性普遍增加，因为与对照相比，LLA术后对血栓素类似物U-46619的剂量-反应关系未显著改变。因此，LLA导致清醒犬的肺血管阻力慢性增加。LLA引起的肺血管阻力增加的一个组成部分是由对交感α1-肾上腺素能受体激活的反应性增强介导的。
