Effect of angiotensin II antagonist eprosartan on hyperglycemia-induced activation of intrarenal renin-angiotensin system in healthy humans.
We have previously reported that hyperglycemia in healthy human subjects increased the renal vasodilator response to the angiotensin-converting enzyme inhibitor captopril. This observation raised intriguing possibilities relevant to the pathogenesis of nephropathy in patients with diabetes mellitus. To ascertain whether the effect of captopril was indeed mediated by a reduction in angiotensin II (Ang II) formation, we performed another study in which an Ang II antagonist, eprosartan, was used in place of captopril. Nine healthy subjects were studied in high sodium balance (ie, sodium intake 200 mmol/d). On the first day, the subjects received 600 mg eprosartan orally, and renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured. Glucose was infused intravenously on the second and third study days to increase plasma glucose to a level below the threshold for glycosuria ( approximately 8.8 mmol/L). Eprosartan at a dose of 600 mg or placebo was administered randomly on the second or third study day 1 hour after initiation of glucose infusion. RPF increased (by 76+/-7 mL. min(-1). 1.73 m(-2), P<0.01) in response to sustained moderate hyperglycemia and then increased further (by 147+/-15 mL. min(-1). 1. 73 m(-2), P<0.01) when eprosartan was administered during hyperglycemia. Eprosartan, conversely, did not affect RPF and GFR in normoglycemic subjects. GFR was not affected by either hyperglycemia or eprosartan. Neither plasma renin activity nor plasma Ang II concentration changed during hyperglycemia, suggesting that the hormonal responses responsible for the enhanced renal vasodilator response to eprosartan occurred within the kidney. The enhancement of the renal vasodilator effect of eprosartan during hyperglycemia is consistent with activation of the intrarenal renin-angiotensin system.
Osei
S Y
SY
Departments of Medicine and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. sosei2@mail.med.upenn.edu
Price
D A
DA
Laffel
L M
LM
Lansang
M C
MC
Hollenberg
N K
NK
D000179:Acrylates / Q000494:pharmacology*; D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000097:blood; D003928:Diabetic Nephropathies / Q000209:etiology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013876:Thiophenes
D000179:Acrylates; D007093:Imidazoles; D013876:Thiophenes; D000804:Angiotensin II; C068373:eprosartan; D012083:Renin