학술논문
가토 신장기능에 미치는 K+ 통로 개구제 WAY120491의 영향
Effects of K+ Channel Opener WAY120491 on Renal Function in Rabbits가토 신장기능에 미치는 K+ 통로 개구제 WAY120491의 영향
Effects of K+ Channel Opener WAY120491 on Renal Function in Rabbits가토 신장기능에 미치는 K+ 통로 개구제 WAY120491의 영향
Document Type
Article
Author
Source
Kidney Research and Clinical Practice(구 대한신장학회지). Jan 01, 2003 22(1):53
Subject
Language
Korean
ISSN
2211-9132
Abstract
목적 : 이 연구는 K^+ 통로 개구제(channel opener)가 신장기능에 미치는 영향을 구명하고자 한 것이다. 방법 : 이 연구에서는 benzopyran 유도체 WAY120491의 신혈류역학적 효과와 신세뇨관의 기능에 미치는 영향을 밝히고자 정상 가토와 신성고혈압 가토 (two-kidney on clip Goldblatt hypertensiv rabbits)에서 일측 신동맥내 약물 투여 방법으로 그 효과를 관찰하였다. 결과 : 정상 가토에서 WAY120491의 신동맥내 투여는 전신혈압의 변화 없이 사구체 여과율과 신혈장류량을 용량 의존적으로 증가시켰다. WAY120491은 요량, 유리수분 배설량, 요중 Na^+ 및 K^+ 배설량을 용량 의존적으로 증가시켰다. 소량의 glibenclamide 투여는 WAY120491의 신혈류역학적 효과와 요량 및 유리수분 배설량 증가 효과를 효과적으로 차단하였다. 이때 요중 Na^+ 배설 증가 효과는 glibenclamide에 의하여 차단되지 않았다. 신성고혈압 가토에서 WAY120491은 대조군과 정량적으로 차이 없는 신혈ㄹ 역학적 효과와 신세뇨관 효과를 보였으나 WAY120491 투여 중지 후 관찰돤 요량 감소 효과는 신성고혈압 가토에서는 관찰되지 않았다. 결론 : K^+ 통로 개구제인 WAY120491은 신장내 ATP 의존적인 K^+ 통로를 경유하여 사구체 여과율, 신혈장류량, 요량 및 유리수분배설량 그리고 요중 K^+ 와 Na^+ 배설량의 증가를 일으키며, 이러한 효과는 신성고혈압 가토에서도 비슷하게 나타난다.
Background : K^+ channel opener has been considered as a vasorelaxing agent working through hyperpolarization of vascular smooth muscle cells. Renal tubules-proximal, thick ascending limb of Henle and cortical collecting duct-are the site of the diversity of the K^+ channel. ATP-sensitive K^+ channel has been observed in the apical membranes of the thick ascending limb of Henle and collecting duct, and basolateral membrane of the proximal tubule. It was also shown that K^+ channel opener increased renal hemodynamics and elicited diuretic and natriuretic effects. Methods : To clarify the renal effects of WAY120491, a K^+ channel opener, experiments were performed in unanesthetized normotensive and renal hypertensive rabbits allowing unilateral renal arterial infusion of agent. Results : Intrarenal arterial infusion (0.13, 0.32 and 0.64 ㎍/kg/min), of WAY120941 increassed C_PAH, C_Cr, urine volume, U_NaV, U_KV and C_H2O, Renal hemodynamic effects and increments of urine volume and free water clearance were complately blocked by glibenclamide (8.2 ㎍/kg/min), while increments of U_NaV and FE_Na were not significantly affected. Fenal hemodynamic and tubular effects of WAY120491 were not significantly different in two-kidney one clip Goldblatt hypertensive rabbits from sham-operated rabbits. Conclusions : These results suggest that WAY120491 elicits renal effects through ATP-sensitive K^+ channel in the renal vasculatures and renal tubules and the renal effects of WAT120491 may not be altered in the hypertension.
Background : K^+ channel opener has been considered as a vasorelaxing agent working through hyperpolarization of vascular smooth muscle cells. Renal tubules-proximal, thick ascending limb of Henle and cortical collecting duct-are the site of the diversity of the K^+ channel. ATP-sensitive K^+ channel has been observed in the apical membranes of the thick ascending limb of Henle and collecting duct, and basolateral membrane of the proximal tubule. It was also shown that K^+ channel opener increased renal hemodynamics and elicited diuretic and natriuretic effects. Methods : To clarify the renal effects of WAY120491, a K^+ channel opener, experiments were performed in unanesthetized normotensive and renal hypertensive rabbits allowing unilateral renal arterial infusion of agent. Results : Intrarenal arterial infusion (0.13, 0.32 and 0.64 ㎍/kg/min), of WAY120941 increassed C_PAH, C_Cr, urine volume, U_NaV, U_KV and C_H2O, Renal hemodynamic effects and increments of urine volume and free water clearance were complately blocked by glibenclamide (8.2 ㎍/kg/min), while increments of U_NaV and FE_Na were not significantly affected. Fenal hemodynamic and tubular effects of WAY120491 were not significantly different in two-kidney one clip Goldblatt hypertensive rabbits from sham-operated rabbits. Conclusions : These results suggest that WAY120491 elicits renal effects through ATP-sensitive K^+ channel in the renal vasculatures and renal tubules and the renal effects of WAT120491 may not be altered in the hypertension.