BACKGROUND: To elucidate the effect of the angiotensin type 1 (AT1) receptor antagonist (AT1RA) eprosartan (E) on renal hemodynamics in normotensive and borderline hypertensive subjects, we investigated the hormonal and renal hemodynamic responses during cardiopulmonary stress testing. METHODS: In a prospective, double-blind, randomized, placebo-controlled crossover study, the effects of E on renal plasma flow (RPF), renal blood flow (RBF), glomerular filtration rate (GFR), and the concentration of angiotensin II (Ang II) levels were measured with the subjects at rest and during perturbation of cardiopulmonary baroreceptors using lower body negative pressure (LBNP). Ten normotensive male subjects (NT) versus 14 males with mild hypertension (HT), matched for age and body mass index, who were all free of any medication, were randomly assigned to receive placebo or E 600 mg/day PO for seven days (intake phase 1). After a washout period of four weeks the subjects started the intake of the other substance for seven days in a crossover manner (intake phase 2). The measurements were taken on day 7 of both intake phases. RESULTS: During the LBNP test, RPF and RBF were reduced significantly in all subjects; GFR, however, decreased significantly during cardiopulmonary stress testing in the subjects taking the placebo (P < 0.05) and remained unchanged in those under treatment with AT1RA. Ang II levels increased significantly during cardiopulmonary stress test only in the subjects with hypertension who were on placebo, whereas the Ang II levels did not change in normotensive subjects or those treated with the AT1RA. CONCLUSIONS: The data confirm that with cardiovascular stress simulating orthostasis or volume depletion, subjects with AT1RA can maintain their GFR level, suggesting that AT1RA potentially is renoprotective. Additionally, the neurohumoral system is activated after cardiovascular stress in subjects even at an early stage of hypertension.