title: Blood pressure early in diabetes depends on a balance between glomerular filtration rate and the renin-angiotensin system.
abstract: Onset of diabetes increases plasma renin activity (PRA) and glomerular filtration rate (GFR), but blood pressure (BP) is normal. In this study, a 70% surgical reduction in kidney mass (RK) was used to decrease baseline GFR and to prevent hyperfiltration during diabetes, and angiotensin converting enzyme inhibitors (ACEI) were used to inhibit angiotensin II (AngII) production, to test the hypothesis that a balance between GFR and AngII is required for normal BP early in diabetes. Diabetes was induced with streptozotocin (STZ) (35 mg/kg intravenously); and after 7 days of hyperglycemia (range: 408 to 486 mg/dL), insulin was intravenously infused continuously for a 4-day normoglycemic recovery period. In normal kidney (NK) rats, diabetes increased PRA (2.4 +/- 0.6 to 4.6 +/- 0.5 ngAI/mL/h) and GFR (2.9 +/- 0.1 to 3.5 +/- 0.2 mL/min), and there was no change in mean arterial pressure (MAP) (89 +/- 1 v 91 +/- 1 mm Hg, measured 18 h/day). There was no change in either GFR or AngII during diabetes in RK+ACEI rats, and their MAP also did not change. Thus, the maintenance of normal MAP was accompanied by a balance between GFR and AngII in both of those groups. In NK+ACEI rats, however, GFR increased significantly with no change in AngII, and MAP decreased significantly during diabetes by approximately 8 mm Hg. In RK rats, PRA increased (0.5 +/- 0.1 to 2.6 +/- 0.5) but GFR did not increase, and MAP increased significantly by approximately 16 mm Hg. All rats were in sodium balance by day 4 of diabetes. These data support the hypothesis that normotension early in diabetes requires a balance between the increased AngII and GFR, and that BP will increase if AngII increases but GFR does not.
authors.affiliation: Department of Physiology and the Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912-3000, USA.
authors.forename: Modesto
authors.initials: M
authors.lastname: Rojas
authors.forename: Tracy D
authors.initials: TD
authors.lastname: Bell
authors.forename: LaShon C
authors.initials: LC
authors.lastname: Sturgis
authors.forename: Vanessa
authors.initials: V
authors.lastname: Springfield
authors.forename: Rajiv
authors.initials: R
authors.lastname: Janardhanan
authors.forename: Cassandra
authors.initials: C
authors.lastname: Fleming
authors.forename: Michael W
authors.initials: MW
authors.lastname: Brands
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000503:physiopathology* / Q000652:urine; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D002216:Captopril; D012964:Sodium; D012083:Renin