Baudouin S V, Evans T W
Department of Anaesthesia and Intensive Care, National Heart and Lung Institute, London, UK.
Crit Care Med. 1993 May;21(5):740-6. doi: 10.1097/00003246-199305000-00018.
The effect of hypercapnia on pulmonary vascular tone is controversial with evidence for both a vasoconstrictor and vasodilator action. The objective of this study was to investigate the possibility that this dual response to CO2 could be explained by a direct constrictor action on smooth muscle and an indirect dilator action via the release of endothelium-derived relaxing factor. The effect of ventilation with hypercapnia (FICO2 0.15) on pulmonary pressor response to hypoxia (FIO2 0.3) was investigated.
Prospective, randomized study.
The National Heart and Lung Institute, UK.
The isolated, blood-perfused rat lung.
Angiotensin-II and a blocker of endothelium-derived relaxing factor synthesis, NG-monomethyl-L-arginine (L-NMMA).
The vasomotor effect of hypercapnia depended on pulmonary arterial pressure. Under resting tone, CO2 acted as a mild constrictor (change in mean pulmonary arterial pressure from 14 +/- 2 to 15 +/- 2 mm Hg, n = 4; p < .05. At increased tone, induced either by hypoxia or Angiotensin-II, CO2 was a vasodilator. Thus, hypoxia increased mean pulmonary arterial pressure from 17 +/- 2 to 32 +/- 2 mm Hg (n = 8; p < .01), but simultaneous ventilation with hypoxia and hypercapnia reduced this by 16 +/- 1% (p < .01). Angiotensin-II (1 microgram) increased pulmonary arterial pressure from 14 +/- 2 to 39 +/- 5 mm Hg (n = 8; p < .01), but with hypercapnia, this angiotensin-induced pulmonary vasoconstriction was reduced by 18 +/- 6% (p < .001). The reduction in hypoxic pulmonary vasoconstriction induced by hypercapnia was not significantly different from that seen with Angiotensin-II hypercapnia. Blocking endothelium-derived relaxing factor synthesis using 30 microM NG-monomethyl-L-arginine did not significantly change either basal pulmonary arterial pressure or the response to hypercapnia, but increased hypoxic pulmonary vasoconstrictor by 24 +/- 4% (n = 4; p < .01). There was no significant difference between the change in hypoxic pulmonary vasoconstriction induced by hypercapnia after saline control (21 +/- 8% decrease) and the change in hypoxic pulmonary vasoconstriction caused by CO2 after 30 microM L-NMMA (25 +/- 10% decrease, p < .05, n = 8).
Endothelium-derived relaxing factor seems unlikely to specifically modulate CO2-induced vasodilation in the rat pulmonary circulation.
高碳酸血症对肺血管张力的影响存在争议，有证据表明其既有血管收缩作用，也有血管舒张作用。本研究的目的是探讨对二氧化碳的这种双重反应是否可以通过对平滑肌的直接收缩作用和通过释放内皮源性舒张因子的间接舒张作用来解释。研究了高碳酸血症通气（FICO2 0.15）对低氧（FIO2 0.3）引起的肺升压反应的影响。
前瞻性、随机研究。
英国国家心肺研究所。
离体、血液灌注的大鼠肺。
血管紧张素-II和内皮源性舒张因子合成阻滞剂N-甲基-L-精氨酸（L-NMMA）。
高碳酸血症的血管舒缩作用取决于肺动脉压。在静息张力下，二氧化碳起轻度收缩作用（平均肺动脉压从14±2 mmHg变为15±2 mmHg，n = 4；p < 0.05）。在由低氧或血管紧张素-II诱导的张力增加时，二氧化碳是一种血管舒张剂。因此，低氧使平均肺动脉压从17±2 mmHg升高至32±2 mmHg（n = 8；p < 0.01），但低氧和高碳酸血症同时通气使该值降低了16±1%（p < 0.01）。血管紧张素-II（1微克）使肺动脉压从14±2 mmHg升高至39±5 mmHg（n = 8；p < 0.01），但在高碳酸血症时，这种血管紧张素诱导的肺血管收缩降低了18±6%（p < 0.001）。高碳酸血症诱导的低氧性肺血管收缩的降低与血管紧张素-II高碳酸血症时所见的降低无显著差异。使用30微摩尔N-甲基-L-精氨酸阻断内皮源性舒张因子合成，对基础肺动脉压或对高碳酸血症的反应均无显著改变，但使低氧性肺血管收缩增加了24±4%（n = 4；p < 0.01）。生理盐水对照后高碳酸血症诱导的低氧性肺血管收缩的变化（降低21±8%）与30微摩尔L-NMMA后二氧化碳引起的低氧性肺血管收缩的变化（降低25±10%，p < 0.05，n = 8）之间无显著差异。
内皮源性舒张因子似乎不太可能特异性调节大鼠肺循环中二氧化碳诱导的血管舒张。
