Amorena C, Castro A F
Instituto de Investigaciones Cardiológicas, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Am J Physiol. 1997 Feb;272(2 Pt 2):R691-4. doi: 10.1152/ajpregu.1997.272.2.R691.
Guanosine 3',5'-cyclic monophosphate (cGMP), a nitric oxide mediator, stimulates Na+/H+ exchange in brush-border vesicles of the renal cortex. The aim of the present work was to test whether the endothelium of the peritubular capillaries modulated the rate of proximal luminal acidification through the release of endothelium-derived nitric oxide (EDNO). Perfusion of the tubule lumen with dibutyryl cGMP increased net proton flux (J(H)). Two agents that elicit EDNO production, bradykinin (BK) and carbamylcholine (Cch), increased J(H) when added to the peritubular capillary perfusate. Bradykinin did not affect J(H) when the peritubular capillaries and the lumen were perfused with Na-free solution. Methylene blue (MB) and N(G)-nitro-L-arginine methyl ester (L-NAME) blocked the elevation in J(H) by Cch and also decreased basal J(H). Bradykinin increased cGMP content of isolated proximal convoluted tubules, but only if they were coincubated with endothelial cells. This effect of BK was blocked by L-NAME. The results suggest that the endothelium of the peritubular capillaries affects proximal tubule acidification through changes of cGMP in proximal tubule cells, probably via stimulation of Na+/H+ exchanger.
3',5'-环磷酸鸟苷(cGMP)是一种一氧化氮介质,可刺激肾皮质刷状缘小泡中的Na+/H+交换。本研究的目的是测试肾小管周围毛细血管内皮是否通过释放内皮衍生的一氧化氮(EDNO)来调节近端管腔酸化的速率。用二丁酰cGMP灌注肾小管腔可增加净质子通量(J(H))。两种可引发EDNO产生的物质,缓激肽(BK)和氨甲酰胆碱(Cch),添加到肾小管周围毛细血管灌流液中时可增加J(H)。当肾小管周围毛细血管和管腔用无钠溶液灌注时,缓激肽不影响J(H)。亚甲蓝(MB)和N(G)-硝基-L-精氨酸甲酯(L-NAME)可阻断Cch引起的J(H)升高,并且还降低基础J(H)。缓激肽可增加分离的近端曲管的cGMP含量,但前提是它们与内皮细胞共同孵育。BK的这种作用被L-NAME阻断。结果表明,肾小管周围毛细血管内皮可能通过刺激Na+/H+交换体,改变近端小管细胞中的cGMP,从而影响近端小管酸化。