Angiotensinase A gene expression and enzyme activity in isolated glomeruli of diabetic rats.
One of the characteristics of early diabetic nephropathy is glomerular hyperfiltration and hyperperfusion. Many factors have been suggested to induce glomerular hyperperfusion among which are an increased production of vasodilatory prostanoids, an increased synthesis of nitric oxide, a reduced responsiveness of afferent glomerular arterioles to vasoconstrictor stimuli due to diabetic metabolic disturbances and a decreased receptor density for angiotensin II. It has been known for years that angiotensin II is formed locally due to the local activation of the renin angiotensin system. The local angiotensin II concentration, however, is not only regulated by the synthesis rate but also by the local degradation through activation of an aminopeptidase. The main finding of the present study was that the mRNA expression and activity of the angiotensin II degrading enzyme, angiotensinase A, was increased twofold in diabetic rats at 5 weeks and that the increase in mRNA expression was suppressed by insulin therapy and short-term treatment with the angiotensin II antagonist saralasin, whereas angiotensinase A enzyme activity was only reduced by saralasin and not by insulin. These results demonstrate that the angiotensin II degrading exopeptidase angiotensinase A is activated in diabetic glomeruli. This increased activity may be an additional mechanism to explain glomerular hyperfiltration and hyperperfusion in early diabetic nephropathy.
Thaiss
F
F
Department of Internal Medicine, University Hospital, Hamburg, Germany.
Wolf
G
G
Assad
N
N
Zahner
G
G
Stahl
R A
RA
D000419:Albuminuria; D000626:Aminopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D005919:Glomerular Filtration Rate; D043384:Glutamyl Aminopeptidase; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007328:Insulin / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000473:pathology; D007700:Kinetics; D008297:Male; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D012504:Saralasin / Q000494:pharmacology; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D000804:Angiotensin II; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase; D012504:Saralasin