We determined whether postnatal pulmonary hypertension induced by 70% of pregnancy at high altitude (HA) persists once the offspring return to sea level and investigated pulmonary vascular mechanisms operating under these circumstances. Pregnant ewes were divided into two groups: conception, pregnancy, and delivery at low altitude (580 m, LLL) and conception at low altitude, pregnancy at HA (3,600 m) from 30% of gestation until delivery, and return to lowland (LHL). Pulmonary arterial pressure (PAP) was measured in vivo. Vascular reactivity and morphometry were assessed in small pulmonary arteries (SPA). Protein expression of vascular mediators was determined. LHL lambs had higher basal PAP and a greater increment in PAP after NG-nitro-l-arginine methyl ester (20.9 ± 1.1 vs. 13.7 ± 0.5 mmHg; 39.9 ± 5.0 vs. 18.3 ± 1.3 mmHg, respectively). SPA from LHL had a greater maximal contraction to K+ (1.34 ± 0.05 vs. 1.16 ± 0.05 N/m), higher sensitivity to endothelin-1 and nitroprusside, and persistence of dilatation following blockade of soluble guanylate cyclase. The heart ratio of the right ventricle-to-left ventricle plus septum was higher in the LHL relative to LLL. The muscle area of SPA (29.3 ± 2.9 vs. 21.1 ± 1.7%) and the protein expression of endothelial nitric oxide synthase (1.7 ± 0.1 vs. 1.1 ± 0.2), phosphodiesterase (1.4 ± 0.1 vs. 0.7 ± 0.1), and Ca2+-activated K+ channel (0.76 ± 0.16 vs. 0.30 ± 0.01) were greater in LHL compared with LLL lambs. In contrast, LHL had decreased heme oxygenase-1 expression (0.82 ± 0.26 vs. 2.22 ± 0.44) and carbon monoxide production (all P < 0.05). Postnatal pulmonary hypertension induced by 70% of pregnancy at HA promotes cardiopulmonary remodeling that persists at sea level.
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机译:我们确定了后代重返海平面后,由70%的高海拔妊娠引起的产后肺动脉高压是否继续存在,并调查了在这些情况下的肺血管机制。怀孕的母羊分为两组:低胎妊娠,妊娠和分娩(580 m,LLL)和低胎妊娠;从妊娠的30%到分娩,在HA(3,600 m)妊娠,然后返回低地(LHL) )。在体内测量肺动脉压(PAP)。在小肺动脉(SPA)中评估血管反应性和形态。确定了血管介质的蛋白表达。在N G sup>-硝基-1-精氨酸甲酯后,LHL羔羊的基础PAP较高且PAP增幅更大(20.9±1.1 vs. 13.7±0.5 mmHg; 39.9±5.0 vs. 18.3±1.3 mmHg , 分别)。 LHL的SPA对K + sup>的最大收缩率更大(1.34±0.05对1.16±0.05 N / m),对内皮素-1和硝普钠的敏感性更高,并且在可溶性鸟苷酸酯被阻断后仍持续扩张环化酶。相对于LLL,LHL中右心室与左心室加隔膜的心率更高。 SPA的肌肉面积(29.3±2.9对21.1±1.7%)和内皮一氧化氮合酶的蛋白质表达(1.7±0.1对1.1±0.2),磷酸二酯酶(1.4±0.1对0.7±0.1)和Ca与LLL羔羊相比,LHL中 2 + sup>激活的K + sup>通道(0.76±0.16 vs. 0.30±0.01)更大。相反,LHL降低了血红素加氧酶-1的表达(0.82±0.26 vs. 2.22±0.44)和一氧化碳的产生(所有P <0.05)。 HA怀孕70%引起的产后肺动脉高压促进了在海平面持续存在的心肺重构。
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