Sy. Osei et al., Effect of angiotensin II antagonist eprosartan on hyperglycemia-induced activation of intrarenal renin-angiotensin system in healthy humans, HYPERTENSIO, 36(1), 2000, pp. 122
Citations number
25
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
We have previously reported that hyperglycemia in healthy human subjects in
creased the renal vasodilator response to the angiotensin-converting enzyme
inhibitor captopril. This observation raised intriguing possibilities rele
vant to the pathogenesis of nephropathy in patients with diabetes mellitus.
To ascertain whether the effect of captopril was indeed mediated by a redu
ction in angiotensin II (Ang II) formation, we performed another study in w
hich an Ang II antagonist, eprosartan, was used in place of captopril. Nine
healthy subjects were studied in high sodium balance (ie, sodium intake 20
0 mmol/d). On the first day, the subjects received 600 mg eprosartan orally
, and renal plasma flow (RPF) and glomerular filtration rate (GFR) were mea
sured. Glucose was infused intravenously on the second and third study days
to increase plasma glucose to a level below the threshold for glycosuria (
approximate to 8.8 mmol/L). Eprosartan at a dose of 600 mg or placebo was a
dministered randomly on the second or third study day 1 hour after initiati
on 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 wa
s administered during hyperglycemia. Eprosartan, conversely, did not affect
RPF and GFR in normoglycemic subjects. GFR was not affected by either hype
rglycemia or eprosartan. Neither plasma renin activity nor plasma Ang II co
ncentration changed during hyperglycemia, suggesting that the hormonal resp
onses responsible for the enhanced renal vasodilator response to eprosartan
occurred within the kidney. The enhancement of the renal vasodilator effec
t of eprosartan during hyperglycemia is consistent with activation of the i
ntrarenal renin-angiotensin system.