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(Hypertension. 1997;30:240-246.)
© 1997 American Heart Association, Inc.

Articles

Renal Hemodynamic Response to an Angiotensin II Antagonist, Eprosartan, in Healthy Men

Deborah A. Price; Jose Mario De'Oliveira; Naomi D. L. Fisher; ; Norman K. Hollenberg

From the Departments of Medicine and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.

Abstract In view of the vasodilator potential of angiotensin-converting enzyme (ACE) inhibition via prostaglandins and kinins, we asked why renin inhibition induces a larger renal vasodilator response than ACE inhibitors in healthy humans in earlier studies. One possibility was that there was a more complete blockade of the renin system, which could also be achieved by an angiotensin II antagonist, eprosartan. We measured the hormonal and renal hemodynamic responses to eprosartan doses, from 10 to 400 mg in 9 healthy young men in balance on a 10-mmol/d sodium intake. The threshold eprosartan dose to influence renal perfusion was <10 mg, and the 100-mg dose induced a near-maximal vasodilator response of 135±19.7 mL · min^-1 · 1.73 m². When the dose was increased to 400 mg, there was a modest additional increase of 147±57 mL · min^-1 · 1.73 m^–2. A highly significant dose-related fall in arterial blood pressure occurred (r=-.97; P<.001), with no indication of a maximal response at 400 mg. In 6 additional subjects, we compared responses to eprosartan on a high salt and a low salt diet. The renal response to 200 mg eprosartan on a high salt diet, 26.0±6.6 mL · min^-1 · 1.73 m^–2, was significantly less than that seen with the low salt diet (P<.001). There was no renal partial agonist angiotensin-like effect of eprosartan. Eprosartan reduced sharply the pressor, renal vascular, and hormonal responses to exogenous angiotensin II. The renal vasodilator response to the angiotensin II antagonist eprosartan closely resembles responses to renin inhibition and exceeds previously reported responses to ACE inhibitors. Thus, eprosartan probably exerted its effect via the angiotensin receptor. More complete blockade of the renin system can be achieved by pharmacological interruption at this level, a finding that could have therapeutic implications.

Key Words: angiotensin II • aldosterone • renin • antihypertensive agents • renal circulation

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