Thomas G D, O'Hagan K P, Zambraski E J
Department of Biology, Rutgers University, New Brunswick, N.J. 08903.
Hypertension. 1991 Mar;17(3):357-62. doi: 10.1161/01.hyp.17.3.357.
To determine if the neurotoxin 6-hydroxydopamine could be used to chemically sympathectomize neonatal miniature swine, eight newborn swine were treated with 6-hydroxydopamine beginning on the first day after birth and continuing at regular intervals for the next 6 months. Six littermates served as controls and received vehicle injections. A significant reduction in the pressor response to intravenous tyramine (95%) and in the tissue norepinephrine content of the kidneys, left ventricle, and gastrocnemius muscle (more than 93%) provided evidence for an effective long-term sympathectomy in the 6-hydroxydopamine-treated animals. In addition, the blood pressure response of these young, chemically sympathectomized swine to chronic deoxycorticosterone acetate treatment was evaluated. Mean arterial pressure before deoxycorticosterone was similar in the 6-hydroxydopamine-treated (116 +/- 2 mm Hg) and control (125 +/- 5 mm Hg) groups. One week after deoxycorticosterone, mean arterial pressure had risen significantly by 20-22 mm Hg in both groups. Blood pressure continued to increase in the control group, reaching a value of 163 +/- 6 mm Hg by the third week after treatment. In contrast, mean arterial pressure in the 6-hydroxydopamine group did not increase further during weeks 2 and 3 after deoxycorticosterone. In conclusion, chronic treatment of neonatal swine with 6-hydroxydopamine produced an animal model with an effective, general, peripheral sympathectomy. The significant attenuation of the hypertensive response in these sympathectomized animals lends further support to the hypothesis that an intact sympathetic nervous system is necessary for the full expression of deoxycorticosterone hypertension in miniature swine.
为了确定神经毒素6-羟基多巴胺是否可用于对新生小型猪进行化学性交感神经切除术，八只新生猪从出生后第一天开始用6-羟基多巴胺治疗，并在接下来的6个月内定期持续给药。六只同窝仔猪作为对照，接受赋形剂注射。对静脉注射酪胺的升压反应显著降低（95%），肾脏、左心室和腓肠肌的组织去甲肾上腺素含量显著降低（超过93%），这为6-羟基多巴胺治疗的动物进行了有效的长期交感神经切除术提供了证据。此外，还评估了这些经化学性交感神经切除术的幼猪对慢性醋酸脱氧皮质酮治疗的血压反应。6-羟基多巴胺治疗组（116±2mmHg）和对照组（125±5mmHg）在给予醋酸脱氧皮质酮之前的平均动脉压相似。给予醋酸脱氧皮质酮一周后，两组的平均动脉压均显著升高20-22mmHg。对照组血压持续升高，治疗后第三周达到163±6mmHg。相比之下，6-羟基多巴胺组在给予醋酸脱氧皮质酮后的第2周和第3周平均动脉压没有进一步升高。总之，用6-羟基多巴胺对新生猪进行慢性治疗产生了一种具有有效、全身性外周交感神经切除术的动物模型。这些交感神经切除动物的高血压反应显著减弱，进一步支持了完整的交感神经系统对于小型猪中醋酸脱氧皮质酮高血压的充分表达是必要的这一假说。
