Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/13543
Title: Role of angiotensin II and bradykinin in experimental diabetic nephropathy. Functional and structural studies.
Authors: Allen, Terri J;Cao, Zemin;Youssef, S;Hulthen, U L;Cooper, Mark E
Affiliation: Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg West, Australia.
Issue Date: 1-Oct-1997
Citation: Diabetes; 46(10): 1612-8
Abstract: We explored the relative roles of the suppression of angiotensin II and the prevention of bradykinin degradation in mediating the renoprotective effects of ACE inhibitors in experimental diabetic nephropathy. Over a 24-week period, we studied male Sprague-Dawley diabetic and control rats and Sprague-Dawley diabetic rats treated with the ACE inhibitor ramipril, the angiotensin II-AT1 receptor antagonist valsartan, the bradykinin-B2 receptor antagonist HOE 140 (icatibant), and a combination of ramipril and icatibant. Serial measurements of urinary albumin excretion, blood pressure, and glycated hemoglobin were performed monthly. After 6 months, the animals were killed for the measurement of kidney weight and the assessment of glomerular ultrastructure. Over 24 weeks, urinary albumin excretion showed a continuous rise in the untreated diabetic rats. Both ramipril and valsartan, which were equihypotensive, prevented the increase in urinary albumin excretion over the whole study period. Icatibant therapy did not attenuate the antialbuminuric effect of the ACE inhibitor, nor did it have any effect as the sole therapy. Diabetes was associated with increased glomerular basement membrane thickness, glomerular volume, and total mesangial volume. Both ACE inhibition and angiotensin II receptor antagonism attenuated the glomerular ultrastructural changes to a similar degree. Icatibant did not attenuate the effects of ramipril on glomerular morphology. ACE inhibitors and angiotensin II-AT1 receptor blockers appear to confer similar benefits in experimental diabetic nephropathy, and bradykinin-B2 receptor blockers do not influence this effect. These findings suggest that the blockade of angiotensin II is the major pathway responsible for renoprotection afforded by ACE inhibition in experimental diabetic nephropathy.
Internal ID Number: 9313758
URI: http://ahro.austin.org.au/austinjspui/handle/1/13543
URL: http://www.ncbi.nlm.nih.gov/pubmed/9313758
Type: Journal Article
Subjects: Albuminuria
Angiotensin II.chemistry.physiology
Angiotensin-Converting Enzyme Inhibitors.therapeutic use
Animals
Blood Pressure
Bradykinin.analogs & derivatives.chemistry.pharmacology.physiology
Bradykinin Receptor Antagonists
Diabetes Mellitus, Experimental.pathology.physiopathology
Diabetic Nephropathies.etiology.prevention & control
Kidney.pathology
Kidney Glomerulus.ultrastructure
Male
Organ Size
Ramipril.therapeutic use
Rats
Rats, Sprague-Dawley
Tetrazoles.therapeutic use
Valine.analogs & derivatives.therapeutic use
Appears in Collections:Journal articles

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