Butler D G, Butt D A, Puskas D, Oudit G Y
Department of Zoology, University of Toronto, Ramsay Wright Zoological Laboratories, Ontario, Canada.
J Endocrinol. 1994 Jul;142(1):19-28. doi: 10.1677/joe.0.1420019.
Angiotensin II (ANG II)-mediated catecholamine release and its possible contribution to the pressor response was assessed in baroreceptor-denervated rats. Neonatal male Sprague-Dawley rats were injected with the sympatholytic drug, guanethidine monosulphate (50 mg/kg s.c., 6 days/week) for 40 days. Plasma catecholamine concentrations were measured using a 3H-radioenzymatic assay as follows: (a) before and 30 s after the injection of saline or ANG II (79.3 pmol/kg i.v.), at the peak of the pressor response, then 50 s and 80 s thereafter, in guanethidine-treated (GUAN) and saline-injected (SHAM) rats, and (b) before and after adrenalectomy (ADX), following the same time-sequence for ANG II as in (a). Peak pressor responses to graded doses of ANG II (6.6, 26.4, 53.0 and 79.3 pmol/kg i.v.) were measured in GUAN+ADX and ADX rats. Destruction of peripheral sympathetic nerves was confirmed by measurements of plasma noradrenaline (NA), adrenaline (AD) and dopamine (DA) concentrations and by changes in pressor responses and heart rates following i.v. doses of tyramine. ANG II induced significantly (P < 0.05) greater pressor responses in GUAN+ADX rats than in ADX rats, especially after the 53.0 and 79.3 pmol/kg doses. Plasma AD concentrations increased within seconds after the pressor response to ANG II in both GUAN and SHAM rats but there was no change in plasma NA or DA concentrations (P < 0.05). ANG-II-mediated AD release from the adrenal medulla may contribute to the overall pressor action of the peptide. The vasculature became more sensitive to ANG II at a time when NA and DA depletion occurred following sympathectomy and/or adrenalectomy. This heightened sensitivity to ANG II was not due to a decrease in circulating ANG II in sympathectomized rats because even though plasma renin activity fell from 6.54 +/- 0.52 to 3.77 +/- 0.26 ng ANG I/ml per h it remained within the normal range.
在压力感受器去神经大鼠中评估了血管紧张素II（ANG II）介导的儿茶酚胺释放及其对升压反应的可能作用。新生雄性Sprague-Dawley大鼠皮下注射抗交感神经药物单硫酸胍乙啶（50 mg/kg，每周6天），持续40天。采用3H-放射酶法测定血浆儿茶酚胺浓度如下：（a）在注射生理盐水或ANG II（79.3 pmol/kg静脉注射）前及注射后30秒，在升压反应峰值时，然后在50秒和80秒后，分别测定胍乙啶处理组（GUAN）和注射生理盐水组（SHAM）大鼠的血浆儿茶酚胺浓度；（b）在肾上腺切除（ADX）前后，按照与（a）中ANG II相同的时间顺序测定血浆儿茶酚胺浓度。测定GUAN + ADX组和ADX组大鼠对不同剂量ANG II（6.6、26.4、53.0和79.3 pmol/kg静脉注射）的升压反应峰值。通过测定血浆去甲肾上腺素（NA）、肾上腺素（AD）和多巴胺（DA）浓度以及静脉注射酪胺后升压反应和心率的变化来确认外周交感神经的破坏。ANG II在GUAN + ADX组大鼠中诱导的升压反应显著（P < 0.05）大于ADX组大鼠，尤其是在53.0和79.3 pmol/kg剂量后。在GUAN组和SHAM组大鼠中，对ANG II的升压反应后数秒内血浆AD浓度均升高，但血浆NA或DA浓度无变化（P < 0.05）。ANG II介导的肾上腺髓质AD释放可能有助于该肽的整体升压作用。在交感神经切除术和/或肾上腺切除术后NA和DA耗竭时，血管系统对ANG II变得更加敏感。这种对ANG II的敏感性增强并非由于去交感神经大鼠循环ANG II的减少，因为尽管血浆肾素活性从6.54±0.52降至3.77±0.26 ng ANG I/ml per h，但仍在正常范围内。
