Hom G J, Jandhyala B S
J Pharmacol Exp Ther. 1984 Aug;230(2):275-83.
Cerebroventricular infusion of ouabain (10(-6) M) in cerebrospinal fluid produced significant increases in renal blood flow and reductions in renal vascular resistance in chloralose anesthetized, vagotomized dogs; these renal effects were not accompanied by any changes in arterial blood pressure and heart rate. Infusion of a higher concentration of ouabain (10(-5) M) enhanced significantly blood pressure, heart rate, renal vascular resistance and reduced renal blood flow. The renal vasodilator effects precipitated by lower concentration of ouabain have not been documented before and the mechanisms involved in these observations were investigated in the present study. Pretreatment of the dogs with indomethacin did not prevent renal vasodilator effects of ouabain, indicating that prostaglandins were not involved. Acute renal denervation abolished these actions suggesting that these renal vascular effects were mediated neurogenically. In the dogs, pretreated with i.v. sulpiride, a dopamine receptor antagonist, central infusions of ouabain (10(-6) M) produced significant increases in blood pressure, renal vascular resistance and reduced renal blood flow. These effects were opposite to those noted in control animals. These data suggested that vasodilatation induced by central ouabain was mediated via activation of renal dopaminergic fibers. Prior intraventricular infusion of small doses of sulpiride that antagonized central dopamine receptors, without affecting peripheral sites, also prevented but did not reverse the renal effects of ouabain. Selective blockade of central alpha receptors with phentolamine also abolished ouabain-induced renal vasodilatation. In addition, after central alpha receptor blockade ouabain increased arterial blood pressure. In the dogs pretreated with i.v. phentolamine, cerebroventricular ouabain did not produce any changes in these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
在脑脊液中向氯醛糖麻醉、迷走神经切断的犬脑室内注入哇巴因(10⁻⁶ M)可显著增加肾血流量并降低肾血管阻力;这些肾脏效应并未伴随动脉血压和心率的任何变化。注入更高浓度的哇巴因(10⁻⁵ M)可显著提高血压、心率、肾血管阻力并减少肾血流量。较低浓度哇巴因引发的肾血管舒张作用此前未见报道,本研究对这些观察结果所涉及的机制进行了研究。用吲哚美辛预处理犬并未阻止哇巴因的肾血管舒张作用,表明前列腺素不参与其中。急性肾去神经支配消除了这些作用,提示这些肾血管效应是由神经介导的。在用静脉注射舒必利(一种多巴胺受体拮抗剂)预处理的犬中,向脑室内注入哇巴因(10⁻⁶ M)可显著提高血压、肾血管阻力并减少肾血流量。这些效应与对照动物中观察到的相反。这些数据表明,中枢性哇巴因诱导的血管舒张是通过激活肾多巴胺能纤维介导的。事先脑室内注入小剂量舒必利拮抗中枢多巴胺受体,而不影响外周部位,也可预防但不能逆转哇巴因的肾脏效应。用酚妥拉明选择性阻断中枢α受体也消除了哇巴因诱导的肾血管舒张。此外,在中枢α受体阻断后,哇巴因可升高动脉血压。在用静脉注射酚妥拉明预处理的犬中,脑室内注入哇巴因对这些参数未产生任何变化。(摘要截短于250字)