Cardiovascular agents affect the tone of pulmonary arteries and veins in precision-cut lung slices.

Cardiovascular agents affect the tone of pulmonary arteries and veins in precision-cut lung slices.
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DOI:
10.1371/journal.pone.0029698
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Martin C
Martin C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Rieg AD;Rossaint R;Uhlig S;Martin C

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心血管药物在心力衰竭的治疗中起着关键作用。除了对心室收缩和全身后负荷的作用外,它们还影响肺的动脉和静脉。虽然这些影响在心力衰竭合并肺动脉高压或肺水肿时是至关重要的,但它们的定义很不明确,特别是在肺静脉。因此,我们研究了肾上腺素受体激动剂、血管加压素和血管紧张素II对肺血管的影响。制作豚鼠肺精切切片,用电视显微镜成像。分析心血管药物在肺动、静脉中的量效曲线。肺静脉对α1激动剂(收缩)和β2激动剂(松弛)的反应强于动脉。值得注意的是,抑制β2肾上腺素受体揭示了去甲肾上腺素和肾上腺素在肺静脉中模拟α1的作用。血管加压素和血管紧张素II分别通过V1a和AT1受体收缩肺静脉,而不影响肺动脉。加压素和去甲肾上腺素联合β-2抑制可引起肺静脉收缩。如果适用于人类,这些治疗将增加毛细血管静水压和肺水肿,这表明它们在左心衰竭中谨慎使用。反之亦然,AT1受体拮抗剂对肺静脉收缩的预防作用可能与其在左心衰竭中的有益作用有关。此外,α-1类似物可能通过收缩肺动脉而加重肺动脉高压和右心衰竭,而血管加压素可能不会。
Cardiovascular agents are pivotal in the therapy of heart failure. Apart from their action on ventricular contractility and systemic afterload, they affect pulmonary arteries and veins. Although these effects are crucial in heart failure with coexisting pulmonary hypertension or lung oedema, they are poorly defined, especially in pulmonary veins. Therefore, we investigated the pulmonary vascular effects of adrenoceptor agonists, vasopressin and angiotensin II in the model of precision-cut lung slices that allows simultaneous studies of pulmonary arteries and veins. Precision-cut lung slices were prepared from guinea pigs and imaged by videomicroscopy. Concentration-response curves of cardiovascular drugs were analysed in pulmonary arteries and veins. Pulmonary veins responded stronger than arteries to α1-agonists (contraction) and β2-agonists (relaxation). Notably, inhibition of β2-adrenoceptors unmasked the α1-mimetic effect of norepinephrine and epinephrine in pulmonary veins. Vasopressin and angiotensin II contracted pulmonary veins via V1a and AT1 receptors, respectively, without affecting pulmonary arteries. Vasopressin and (nor)epinephrine in combination with β2-inhibition caused pulmonary venoconstriction. If applicable in humans, these treatments would enhance capillary hydrostatic pressures and lung oedema, suggesting their cautious use in left heart failure. Vice versa, the prevention of pulmonary venoconstriction by AT1 receptor antagonists might contribute to their beneficial effects seen in left heart failure. Further, α1-mimetic agents might exacerbate pulmonary hypertension and right ventricular failure by contracting pulmonary arteries, whereas vasopressin might not.
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