Atrial natriuretic peptide and glomerular hyperfiltration during onset of spontaneous diabetes mellitus.
The mechanisms responsible for the elevation of glomerular filtration rate (GFR) in early stages of insulin-dependent diabetes mellitus (IDDM) are undefined. The objectives of this study were to define the temporal pattern of onset of glomerular hyperfiltration in the spontaneously diabetes-prone (BB/DP) rat and to evaluate the possible role of atrial natriuretic peptide (ANP) as the primary mediator of the observed alterations in renal hemodynamics. GFR was significantly higher (1.38 +/- 0.07 ml.min-1 x g-1; n = 5) in moderately hyperglycemic BB/DP rats (blood glucose > 270 mg/dl) 14 days after the onset of IDDM compared with age-matched diabetes-resistant rats (BB/DR), which averaged 1.03 +/- 0.07 ml.min-1 x g-1 (n = 7). Circulating ANP levels in moderately hyperglycemic BB/DP rats 1, 7, and 14 days after onset of IDDM were within the normal range, averaging 100 +/- 21, 57 +/- 12, and 65 +/- 6 pg/ml, respectively, and were not significantly different (P > 0.05) from ANP levels in age-matched normoglycemic BB/DR rats. To further test the role of ANP in glomerular hyperfiltration, an ANP receptor antagonist was infused into anesthetized BB/DP rats (n = 10) 14 days after onset of IDDM, after baseline measurements of mean arterial pressure, renal hemodynamics, and renal fluid and electrolyte excretions. ANP receptor antagonism caused a significant reduction in mean arterial pressure from 120 +/- 3 to 103 +/- 2 mmHg; however, there were no significant effects of ANP receptor blockade on GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
Okwueze
M I
MI
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Opgenorth
T J
TJ
von Geldern
T W
TW
Vari
R C
RC
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood* / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006029:Glycosuria; D007113:Immunity, Innate; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011913:Rats, Inbred BB; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors; D012079:Renal Circulation / Q000187:drug effects; D044005:Tetrahydroisoquinolines; D010130:p-Aminohippuric Acid
D001786:Blood Glucose; D010446:Peptide Fragments; D044005:Tetrahydroisoquinolines; C078792:A 71915; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D010130:p-Aminohippuric Acid