Koyama S, Kobayashi T, Sakai A, Yoshimura K
First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Am Rev Respir Dis. 1988 Apr;137(4):779-82. doi: 10.1164/ajrccm/137.4.779.
We examined the effects of cell-permeable dibutyryl cyclic AMP (DBcAMP) on acute hypoxic pulmonary vasoconstriction (HPV) in conscious sheep. Mean left and right atrial, pulmonary, and systemic pressures (Pla, Pra, Ppa, and Psa, mm Hg), cardiac output (CO, L/min), and heart rate were measured continuously. Systemic (SVR) and pulmonary vascular resistances (PVR) were calculated by (Psa-Pra)/CO and (Ppa-Pla)/CO, respectively. Five groups of experiments were performed using the same sheep (n = 6). After a 30-min baseline period, sheep inhaled a hypoxic gas mixture (O2:N2 = 1:9) for 40 min. Pretreatment with DBcAMP (200 micrograms/kg/min) inhibited HPV (Ppa, 12.0 +/- 2.3 to 20.0 +/- 2.3 versus 13.2 +/- 2.5 to 14.3 +/- 1.4 mm Hg, p less than 0.01; PVR, 2.61 +/- 0.81 to 4.15 +/- 1.14 versus 2.30 +/- 0.87 to 2.52 +/- 0.59 mm Hg/L/min, p less than 0.01). DBcAMP treatment (200 micrograms/kg/min) after induction of HPV also significantly attenuated hypoxic pulmonary response (Ppa, 19.0 +/- 1.7 to 14.2 +/- 2.3 mm Hg, p less than 0.01; PVR, 3.92 +/- 0.39 to 2.34 +/- 0.34 mm Hg/L/min, p less than 0.01) without significant decreases in Psa and SVR. Pretreatment with DBcAMP (200 micrograms/kg/min) did not significantly alter pulmonary pressor responses to bolus injections of prostaglandin F2 alpha (PGF2 alpha) (10 micrograms/kg) and norepinephrine (4 micrograms/kg). These results may suggest that intracellular augmentation of cyclic AMP plays a crucial role in modulating HPV.
我们研究了细胞可渗透的二丁酰环磷腺苷（DBcAMP）对清醒绵羊急性低氧性肺血管收缩（HPV）的影响。连续测量平均左、右心房压、肺动脉压和体循环压力（Pla、Pra、Ppa和Psa，单位为mmHg）、心输出量（CO，单位为L/min）和心率。体循环血管阻力（SVR）和肺血管阻力（PVR）分别通过（Psa - Pra）/CO和（Ppa - Pla）/CO计算得出。使用同一批绵羊（n = 6）进行了五组实验。在30分钟的基线期后，绵羊吸入低氧气体混合物（O2:N2 = 1:9）40分钟。用DBcAMP（200微克/千克/分钟）预处理可抑制HPV（Ppa，从12.0±2.3变为20.0±2.3，而对照为13.2±2.5变为14.3±1.4 mmHg，p < 0.01；PVR，从2.61±0.81变为4.15±1.14，而对照为2.30±s0.87变为2.52±0.59 mmHg/L/min，p < 0.01）。在诱导HPV后给予DBcAMP治疗（200微克/千克/分钟）也显著减弱了低氧性肺反应（Ppa从19.0±1.7变为14.2±2.3 mmHg，p < 0.01；PVR，从3.92±0.39变为2.34±0.34 mmHg/L/min，p < 0.01），而Psa和SVR无显著降低。用DBcAMP（200微克/千克/分钟）预处理对前列腺素F2α（PGF2α）（每千克10微克）和去甲肾上腺素（每千克4微克）推注引起的肺血管升压反应无显著影响。这些结果可能表明细胞内环磷腺苷的增加在调节HPV中起关键作用。
