Sugino H, Shimada H
Department of Clinical Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Jpn J Pharmacol. 1987 Nov;45(3):343-8. doi: 10.1254/jjp.45.343.
Effect of isoproterenol on renal uric acid excretion was examined in oxonate-loaded and oxonate-nonloaded rats, using a clearance technique. Oxonate loading was performed by continuous infusion into the femoral vein. Isoproterenol (50 micrograms/kg, i.v.) induced antidiuresis and hyperuricemia accompanied with decreases in urinary excretion rate of uric acid, uric acid clearance, inulin clearance, and uric acid clearance/inulin clearance ratio in oxonate-nonloaded rats. These effects of isoproterenol were inhibited by propranolol (1 mg/kg, i.v.). Very similar results were obtained in oxonate-loaded rats; i.e., systemic blood pressure decreased synchronously with uric acid excretion by isoproterenol. In contrast, phenylephrine (100 micrograms/kg, i.v.) induced hypertensive, diuretic and slightly uricosuric results. In allopurinol-pretreated and oxonate-loaded rats, isoproterenol also decreased renal uric acid excretion and showed a less potent hyperuricemic effect than that observed in the animals not pretreated with allopurinol. In addition, in rats with ligated renal vessels, the hyperuricemic effect of isoproterenol was completely inhibited by allopurinol. These results suggest that isoproterenol-induced hyperuricemia is related not only to the stimulation of uric acid production, but also to the depression of renal uric acid excretion.
采用清除率技术，在注射氧嗪酸钾和未注射氧嗪酸钾的大鼠中研究了异丙肾上腺素对肾脏尿酸排泄的影响。通过股静脉持续输注进行氧嗪酸钾负荷。在未注射氧嗪酸钾的大鼠中，静脉注射异丙肾上腺素（50微克/千克）可引起抗利尿和高尿酸血症，同时伴有尿酸排泄率、尿酸清除率、菊粉清除率及尿酸清除率/菊粉清除率比值降低。异丙肾上腺素的这些作用被静脉注射的普萘洛尔（1毫克/千克）所抑制。在注射氧嗪酸钾的大鼠中获得了非常相似的结果；即异丙肾上腺素引起的尿酸排泄与系统血压同步下降。相比之下，静脉注射去氧肾上腺素（100微克/千克）可引起高血压、利尿及轻度促尿酸尿的结果。在预先用别嘌呤醇处理并注射氧嗪酸钾的大鼠中，异丙肾上腺素也降低了肾脏尿酸排泄，且其高尿酸血症作用比未用别嘌呤醇预处理的动物中观察到的作用弱。此外，在肾血管结扎的大鼠中，异丙肾上腺素的高尿酸血症作用被别嘌呤醇完全抑制。这些结果表明，异丙肾上腺素诱导的高尿酸血症不仅与尿酸生成的刺激有关，还与肾脏尿酸排泄的抑制有关。
