(Hypertension. 2000;36:122.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Effect of Angiotensin II Antagonist Eprosartan on Hyperglycemia-Induced Activation of Intrarenal Renin-Angiotensin System in Healthy Humans
From the Departments of Medicine and Radiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Suzette Y. Osei, MD, PhD, University of Pennsylvania School of Medicine, Division of Endocrinology, Diabetes and Metabolism, 778 Clinical Research Building, 415 Curie Blvd, Philadelphia, PA 19104. E-mail sosei2{at}mail.med.upenn.edu
Abstract—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 (
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.
Key Words: hemodynamics • kidney • glomerular filtration rate • hyperglycemia • sodium • angiotensin II
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