(Hypertension. 1996;28:961-966.)
© 1996 American Heart Association, Inc.
Articles |
Losartan Blocks Aldosterone and Renal Vascular Responses to Angiotensin II in Humans
Vanderbilt University Medical Center, Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Nashville, Tenn.
In vitro and animal studies have demonstrated that the effect of angiotensin II (Ang II) on aldosterone is mediated through the Ang II type 1 receptor. However, it has been difficult to demonstrate an effect of Ang II type 1 receptor blockade on aldosterone levels in human studies. One possible explanation is that subjects have not been studied under salt-controlled conditions. Therefore, we examined the effects of losartan on the aldosterone and renal plasma flow responses to Ang II infusion in six normotensive subjects under low and high salt conditions. Ang II was infused in graded doses (0.3 to 10 ng/kg per minute) in the presence and absence of losartan (a single 50-mg oral dose). Renal plasma flow was assessed by measurement of para-aminohippurate clearance. Blood pressure, plasma aldosterone levels (low salt conditions only), and para-aminohippurate clearance were measured before and after each Ang II dose. Losartan had no effect on baseline systolic pressure but attenuated the systolic pressure response to exogenous Ang II during both low salt (0.7±1.9 versus 6.7±1.4 mm Hg, P=.001) and high salt (2.0±1.9 versus 12.3±2.1 mm Hg, P=.006) conditions. Under low salt conditions, losartan reduced the baseline plasma aldosterone level from 1135±204 to 558±102 pmol/L (P=.015) and blocked the aldosterone response to Ang II (-49±110 versus +436±83 pmol/L, P=.019). During high salt conditions, losartan had no effect on baseline renal plasma flow but attenuated the renal plasma flow response to Ang II (-90.1±15.1 versus -185.1±2.6 mL/min per 1.73 m2, P=.013). These data confirm that losartan lowers both basal and exogenous Ang II–stimulated aldosterone levels under low salt conditions. Losartan does not significantly affect baseline renal plasma flow but does attenuate the renal plasma flow response to exogenous Ang II under high salt conditions.
Key Words: losartan • angiotensin II • receptors, angiotensin • aldosterone • renal circulation
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