The Effect of Captopril on Urinary Protein Excretion and Anionic Sites on Glomerular Basement Membrane in Puromycin Aminonucleoside Nephrosis in Rats

Park, Moon Soo; Lee, Hye Sun; Choi, Yong; Ko, Kwang Wook

Abstract

Captopril, an orally active ACE inhibitor, has been known to attenuate the protein excretion in animal model such as puromycin-aminonucleoside(PAN)- induced nephrotic rats or partially nephrectomized rats and clinical study, but the exact mechanism of its action has not been elucidated yet. Captopril interacts with several important vasoactive agents such as angiotensin, bradykinin, prostaglandin, etc., and then can alter the intrarenal hemodynamics. But it is unclear whether the antiproteinuric effect of captopril is mediated by its action on intrarenal hemodynamics. Because it has been found that the depletion of anionic sites(AS) on glomerular basement membrane (GBM) is the important pathophysiologic mechanism in PAN nephrosis, it can be postulated that captopril may reduce the proteinuria by the action on GBM anionic sites. But it needs the morphological evidence. To find out the mechanism of action of captopril on reducing proteinuria and the relationship with GBM anionic sites in PAN nephrosis, the author induced PAN nephrosis by intraperitoneal injection of PAN, (10mg/100g of body weight) in Sprague- Dawley rats and administered captopril per oral route(25mg/day/100g of body weight). GBM anionic sites were stained with polyethyleneimine(PEI) and cuprolinic blue, the cationic markers, and morphometry was done under the electronmicroscope. In PAN nephrotic rats(group A), systemic blood pressure was significantly elevated compared with normal control rats of group C, (157+/-17 vs. 128+/-14 mmHg, p<0.01). Captopril did not lower the systolic blood pressure significantly, but incresed the creatinine clerance(0.37+/-0.17 vs. 0.13+/-0.04ml/min/100g of body weight, P<0.05). In PAN+captopril group (group B), daily urinary excretion of protein began to attenuate from the sixth day compared with PAN group. On the final day of experiment(the 12nd day), captopril reduced the urinary protein excretion below the half of the amount of group A (20.3+/-5.3 vs. 44.1+/-17.1mg/24hr, P<0.01), but which did not decreased to that of normal group(9.7+/-2.7mg/24hr, P<0.01). The anionic sites on lamina rara externa showed reduction in number in group A (11.8+/-1.1/1000nm GBM) compared with normal group(19.3+/-0.7/1000nm, P<0.01), and in group B the loss of GBM anionic sites was significantly attenuated (16.1+/-1.1/1000nm, P<0.01). Captopril acts to reduce urinary protein excretion in PAN nephrotic rats, and which is associated with inhibition of depletion of GBM anionic sites, so that the action on the GBM anionic sites is thought to be one of the important mechanisms of antiproteinuric effect of captopril.