Milanez Maycon I O, Cabral Antônio M, Pires José G P, Bergamaschi Cássia T, Campos Ruy R, Futuro Neto Henrique A, Silva Nyam F
Cardiovascular Division, Department of Physiology, Universidade Federal de São Paulo, Escola Paulista de Medicina, Brazil.
Faculdades Integradas São Pedro, FAESA, Vitória, ES, Brazil.
Heliyon. 2019 Dec 19;5(12):e03066. doi: 10.1016/j.heliyon.2019.e03066. eCollection 2019 Dec.
The contribution of intrarenal alpha-2 adrenergic receptors in mediating the enhanced renal excretory responses evoked by the alpha-2-agonist xylazine was examined in a model of cirrhosis in rats. In sham-operated rats, xylazine (0.2 mg/kg, .) increased diuresis and natriuresis (urine flow, control: 78 ± 12.1, 10 min: 155 ± 17, 20 min: 194 ± 19, 30 min: 146 ± 16, 40 min: 114 ± 13, 50 min: 95 ± 10.5 μl/min/g; urinary sodium excretion, control: 6.75 ± 2.08, 10 min: 7.12 ± 2.1, 20 min: 13.4 ± 4.6, 30 min: 14.6 ± 4.02, 40 min: 12.05 ± 2.35, 50 min: 12.7 ± 2.45 μeq/min/g), which was accompanied by a significant reduction in renal sympathetic nerve activity (RSNA) (control: 100, 10 min: 39.5 ± 5.8, 20 min: 53 ± 8.8, 30 min: 72 ± 7.0, 40 min: 83 ± 5.0, 50 min: 94 ± 6.1 AU). Xylazine (0.2 mg/kg) in cirrhotic animals, despite resulting in a significant reduction in RSNA (control: 100, 10 min: 73 ± 4.3*, 20 min: 70 ± 5.0*, 30 min: 76 ± 7.0*, 40 min: 85 ± 5.5*, 50 min: 92 ± 4.8* AU), was unable to increase natriuresis. A higher dose (20 mg/kg) of xylazine was not capable of increasing natriuresis and diuresis, even in the presence of a robust reduction in RSNA. Renal denervation did not alter the onset and time course of cirrhosis. The results indicated that during the development of cirrhosis, there is an adaptive process that disables the intrarenal alpha-2 adrenoceptor mechanisms that selectively promote water and urinary sodium excretion via a sympathetic renal nerve-independent mechanism. Thus, in cirrhotic rats, the diuresis/natriuresis induced by xylazine is independent on RSNA. Intrarenal and/or hormonal changes are probably involved in the impairment of xylazine-induced diuresis/natriuresis in cirrhosis.
在大鼠肝硬化模型中，研究了肾内α-2肾上腺素能受体在介导α-2激动剂赛拉嗪引起的增强的肾脏排泄反应中的作用。在假手术大鼠中，赛拉嗪（0.2mg/kg，静脉注射）增加了利尿和利钠作用（尿流量，对照组：78±12.1，10分钟：155±17，20分钟：194±19，30分钟：146±16，40分钟：114±13，50分钟：95±10.5μl/min/g；尿钠排泄，对照组：6.75±2.08，10分钟：7.12±2.1，20分钟：13.4±4.6，30分钟：14.6±4.02，40分钟：12.05±2.35，50分钟：12.7±2.45μeq/min/g），同时肾交感神经活动（RSNA）显著降低（对照组：100，10分钟：39.5±5.8，20分钟：53±8.8，30分钟：72±7.0，40分钟：83±5.0，50分钟：94±6.1任意单位）。在肝硬化动物中，赛拉嗪（0.2mg/kg）尽管导致RSNA显著降低（对照组：100，10分钟：73±4.3*，20分钟：70±5.0*，30分钟：76±7.0*，40分钟：85±5.5*，50分钟：92±4.8*任意单位），但不能增加利钠作用。更高剂量（20mg/kg）的赛拉嗪即使在RSNA显著降低的情况下也不能增加利钠和利尿作用。肾去神经支配并未改变肝硬化的发生和进程。结果表明，在肝硬化发展过程中，存在一个适应性过程，使肾内α-2肾上腺素能受体机制失活，该机制通过不依赖肾交感神经的机制选择性促进水和尿钠排泄。因此，在肝硬化大鼠中，赛拉嗪诱导的利尿/利钠作用不依赖于RSNA。肾内和/或激素变化可能参与了肝硬化中赛拉嗪诱导的利尿/利钠作用受损的过程。
