Garr M D, Paller M S
Department of Medicine, University of Minnesota, Minneapolis 55455.
Am J Physiol. 1990 Jan;258(1 Pt 2):F211-7. doi: 10.1152/ajprenal.1990.258.1.F211.
Renal vasoconstriction and hypertension are major side effects of cyclosporine. We tested the acute effects of cyclosporine on renal and systemic vascular reactivity to norepinephrine, angiotensin II, and arginine vasopressin. Renal vascular reactivity was tested in anesthetized Sprague-Dawley rats with denervated kidneys. Renal blood flow was measured with an electromagnetic flow probe in response to graded intra-arterial infusions of vasoconstrictors before and after intravenous administration of cyclosporine. Cyclosporine augmented the decrease in renal blood flow and the increase in renal vascular resistance produced by intrarenal norepinephrine, angiotensin II, and arginine vasopressin. In these studies, systemic blood pressure did not change and cyclosporine caused no direct change in basal renal blood flow. In contrast, in conscious animals, cyclosporine did not increase the pressor response to intravenous norepinephrine or to angiotensin II. Rather, cyclosporine caused enhanced baroreflex slowing of heart rate and a decrease in the pressor response to both norepinephrine and angiotensin II. Even when the baroreceptor reflex was blocked by pentolinium, the pressor response to norepinephrine in cyclosporine-treated animals was diminished compared with vehicle-treated animals. Therefore, although cyclosporine augmented renal vasoconstriction in response to norepinephrine, angiotensin II, and arginine vasopressin, it did not acutely increase the systemic vascular response to these agents. Enhanced renal vascular responsiveness is an additional mechanism for cyclosporine-mediated renal vasoconstriction. Lack of enhanced peripheral vascular responsiveness suggests that hypertension is not likely to be due to direct effects on the systemic vasculature and is more likely to be a consequence of renal functional impairment.
肾血管收缩和高血压是环孢素的主要副作用。我们测试了环孢素对肾脏及全身血管对去甲肾上腺素、血管紧张素II和精氨酸加压素反应性的急性影响。在去神经支配肾脏的麻醉Sprague-Dawley大鼠中测试肾脏血管反应性。在静脉注射环孢素前后，通过电磁血流探头测量肾血流量，以响应动脉内分级输注血管收缩剂。环孢素增强了肾内去甲肾上腺素、血管紧张素II和精氨酸加压素引起的肾血流量减少和肾血管阻力增加。在这些研究中，全身血压没有变化，环孢素也未引起基础肾血流量的直接改变。相反，在清醒动物中，环孢素并未增加对静脉注射去甲肾上腺素或血管紧张素II的升压反应。相反，环孢素导致压力感受器反射引起的心率减慢增强，以及对去甲肾上腺素和血管紧张素II的升压反应降低。即使压力感受器反射被潘托铵阻断，与用赋形剂处理的动物相比，环孢素处理的动物对去甲肾上腺素的升压反应仍减弱。因此，尽管环孢素增强了对去甲肾上腺素、血管紧张素II和精氨酸加压素的肾血管收缩反应，但它并未急性增加对这些药物的全身血管反应。增强的肾血管反应性是环孢素介导的肾血管收缩的另一种机制。外周血管反应性未增强表明高血压不太可能是由于对全身血管系统的直接作用，而更可能是肾功能损害的结果。
