Evidence against increased glomerular pressure initiating diabetic nephropathy.
Studies were carried out to determine whether exaggerated glomerular hydraulic pressure (PG) initiates the development of glomerular pathology and proteinuria in insulin-dependent diabetic rats. Normotensive (WKY) and hypertensive rats (SHR) were made diabetic by streptozotocin injection. One group of SHR diabetic rats was treated with antihypertensive drugs to reduce blood pressure. One week after onset of diabetes, micropuncture determinations of PG, measured by stopped-flow technique, revealed that PG was higher in WKY diabetics than in non-diabetic WKY controls, and that PG was even higher in SHR diabetics (P less than 0.05). Similarly prepared groups of animals were followed for six months, approximately one fifth to one third of the expected life span of these rats. Tail systolic blood-pressure measurements documented continuous severe systolic-hypertension in SHR diabetics, normal pressure in the WKY diabetics and hypotension in the SHR diabetics treated continuously with antihypertensive drugs. Urinary protein excretion, measured monthly, was statistically the same in all groups, with no evidence of a progressive rise in the SHR diabetics. PG measured in two rats from each group after four months of diabetes was similar to values found after one week of diabetes. Semiquantitative histologic scoring of glomerular mesangial expansion after six months of diabetes failed to demonstrate any significant difference between the normotensive WKY diabetics and the hypertensive SHR diabetics. These observations suggest that elevated PG does not in itself initiate glomerular pathology or proteinuria in diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D005919:Glomerular Filtration Rate; D007678:Kidney Glomerulus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D011312:Pressure; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation