Captopril ameliorates the decreased Na+,K(+)-ATPase activity in the retina of streptozotocin-induced diabetic rats.
OBJECTIVE
To examine the effect of captopril, an angiotensin-converting enzyme (ACE) inhibitor, on the activity of retinal sodium-potassium ATPase (Na,K-ATPase) and the activity of ACE in the serum and retina of streptozotocin (STZ)-induced diabetic rats.


METHODS
Experimental diabetes was induced in male Long-Evans rats by a single intraperitoneal injection of STZ (55 mg/kg body weight). Some groups of normal and diabetic animals were treated with captopril (10 mg/kg per day) added to the drinking water for either a week or a month. After 2 and 4 months of diabetes, the specific activity of retinal total Na,K-ATPase was determined. The components of the activity of Na,K-ATPase caused by the alpha 1 and alpha 3 isoforms were pharmacologically separated by their different sensitivity to ouabain. The activity of ACE in the serum and retina was measured by radioassay using benzoyl-gly-gly-gly as substrate (10(5) cpm, 5 mM).


RESULTS
The total Na,K-ATPase activity was decreased significantly after 2 (16%, P < 0.02) and 4 months (15%, P < 0.02) of diabetes. At both time points examined, the activities of the alpha 1-low-ouabain-affinity isoform and the alpha 3-high-ouabain-affinity isoform of retinal Na,K-ATPase were significantly reduced compared to those of age-matched controls (alpha 1, 9% to 14%, P < 0.05; alpha 3, 14% to 19%, P < 0.05 and P < 0.02 respectively). After 1 month of captopril administration, the activities of both Na,K-ATPase isoforms were at control level in 2-month diabetic rats, whereas they were restored only partially in 4-month diabetic rats. In age-matched normal animals, 1 month of captopril treatment did not alter the specific activities of either Na,K-ATPase isoform. One week or 1 month of captopril administration to diabetic rats did not change the activities of retinal Na,K-ATPase isoforms. Serum ACE activity was elevated significantly in both groups of untreated STZ rats (55% and 40%, respectively). One month of captopril administration further increased the ACE levels in 2- and 4-month diabetic rats (101% and 94%, respectively) and also enhanced significantly the serum ACE activity in normal animals (131%) versus the basal values. In contrast, retinal ACE activity was decreased significantly in both groups of untreated STZ rats (approximately 37%). Captopril exerted a significant inhibitory effect on the retinal ACE activity in 2- and 4-month diabetic rats (37% and 31%, respectively) compared to untreated diabetic animals as well as in normal rats (29%).


CONCLUSIONS
These data suggest that stimulation of retinal Na,K-ATPase activity in diabetes is most likely one of the mechanisms through which captopril can improve retinal complications. The effect of captopril seems to be related to local effects in the retina. Whether the inhibition of retinal ACE is part of the mechanism of action of captopril requires further study.
Ottlecz
A
A
College of Optometry, University of Houston, Texas 77204-6052, USA.
Bensaoula
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents; D001786:Blood Glucose / Q000032:analysis; D002216:Captopril / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology; D003930:Diabetic Retinopathy / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013311:Streptozocin
D000806:Angiotensin-Converting Enzyme Inhibitors; D000900:Anti-Bacterial Agents; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010042:Ouabain; D013311:Streptozocin; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D000254:Sodium-Potassium-Exchanging ATPase