Protective Effects of a Small Dose of Captopril on the Reduction of Glomerular Basement Membrane Anionic Sites in Spontaneously Hypertensive Rats with Streptozotocin-Induced Diabetes

• Published in: Journal of diabetes and its complications Vol. 12; no. 3; pp. 170 - 175
• Main Authors: Isogai, Sho, Kameyama, Masaaki, Iso, Kaoru, Yoshino, Gen
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.1998; Elsevier Science
• Subjects: Albuminuria; Animals; Antihypertensive agents; Basement Membrane - metabolism; Basement Membrane - pathology; Basement Membrane - ultrastructure; Biological and medical sciences; Blood Glucose - drug effects; Blood Pressure - drug effects; Body Weight; Captopril - pharmacology; Cardiovascular system; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - physiopathology; Diabetic Angiopathies - metabolism; Diabetic Angiopathies - pathology; Diabetic Angiopathies - physiopathology; Diabetic Nephropathies - physiopathology; Hypertension - physiopathology; Kidney Glomerulus - drug effects; Kidney Glomerulus - metabolism; Kidney Glomerulus - pathology; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Inbred SHR; Asia; Japan; Endocrinopathy; Animal model; Rat; Cardiovascular disease; Male; Assay; Prevention; Anionic site; Association; Complication; Kidney disease; Hypertension; Urine; Urinary system disease; Captopril; Diabetes mellitus; Treatment efficiency; Rodentia; Albumin; Electron microscopy; Pathology; Vertebrata; Chemotherapy; Mammalia; Nephropathy; Animal; Antihypertensive agent; ACE inhibitor
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/S1056-8727(97)00076-7

Angiotensin-converting enzyme (ACE) inhibitors have been used in several clinical trials to slow a progressive decline in glomerular function in patients with diabetic nephropathy independent of their effects on blood pressure. The purpose of this study was to clarify the mechanisms(s) through which an ACE inhibitor, captopril, exerts its protective effect on renal function using spontaneously hypertensive rats (SHR) with streptozotocin (STZ)-induced diabetes. Male SHRs were made diabetic by intravenous injection of STZ (45 mg/kg). One hundred or 25 mg/kg of captopril was administered daily for 4 weeks to them. Urine albumin excretion (UAE) rate was markedly increased in diabetic SHRs, while captopril treatment resulted in a significant suppression of UAE in diabetic SHRs, independent of both its daily dose and effects on blood pressure as well as glycemic control. Examination by electron microscope revealed that the number of anionic sites (AS) in the lamina rara externa per 1000 nm of glomerular basement membrane (GBM) was significantly decreased (22.9 ± 0.2 to 16.1 ± 0.3, p < 0.001), after induction of diabetes, whereas, significant recovery (18.2 ± 0.1, p < 0.001) could be obtained even by the smaller dose (25 mg/kg) of captopril which did not exert either antihypertensive or antidiabetic effect on diabetic SHRs. Thus, we demonstrate here the direct evidence that captopril, an ACE inhibitor, can protect against damage on GBM of diabetic SHR without controlling blood pressure as well as blood glucose level.