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(Hypertension. 2000;36:818.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Normal TGF Responsiveness During Chronic Treatment With Angiotensin-Converting Enzyme Inhibition

Role of AT1 Receptors

Erika Turkstra; Branko Braam; Hein A. Koomans

From the Department of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands.

Correspondence to Branko Braam, MD, PhD, Department of Nephrology and Hypertension, Room F03.226, University Medical Center Utrecht, PO Box 85500, 3508 GA, The Netherlands. E-mail brbraam{at}knoware.nl

Abstract—Acute inhibition of angiotensin II formation by angiotensin-converting enzyme inhibition (ACE-I) attenuates tubuloglomerular feedback (TGF) responsiveness. This has been proposed to facilitate sodium excretion, which contributes to the antihypertensive effects of ACE-I. However, in previous experiments in spontaneously hypertensive Fawn-hooded rats, TGF responses were normal during chronic ACE-I treatment. In the present study, we investigated TGF responsiveness during chronic ACE-I treatment in normotensive rats and the involvement of changes in nitric oxide or angiotensin II activity. Maximum TGF responses were assessed in control Sprague-Dawley rats and in rats acutely (acute ACE-I, 3 µg/min IV) and chronically (chronic ACE-I, 100 mg/L PO 2 to 3 weeks+acute 3 µg/min enalaprilat IV) treated with ACE-I. In all groups, TGF responses were also assessed during late proximal tubular perfusion with 1 mmol/L nitro-L-arginine. In a last group, the chronic ACE-I treatment was combined with acute ACE-I and high doses of intrarenal losartan (acute 3 µg/min enalaprilat IV+50 mg/kg losartan). The maximum TGF responses in acutely treated ACE-I rats were strongly attenuated (0.7±0.4 mm Hg versus 6.5±0.8 mm Hg in control rats, P<0.05). Mean arterial pressure was lower in the chronically treated ACE-I group (107±5 mm Hg versus 126±5 mm Hg in control rats, P<0.05); however, TGF responses were normal (6.4±0.9 mm Hg). Intraluminal nitro-L-arginine infusion did not influence TGF responses during acute ACE-I (2.3±0.4 mm Hg) but enhanced TGF responses during chronic ACE-I to the same extent as in control rats (14.5±2.3 versus 16.7±1.9 mm Hg, NS). In the rats chronically treated with ACE-I with superimposed acute infusion of losartan or chronically treated with losartan, TGF responses were significantly attenuated (1.8±0.8 mm Hg and 2.6±0.8 mm Hg, respectively; P<0.05 versus chronic ACE-I and control). Prolonged administration with ACE-I is associated with normal TGF responses. This phenomenon appears to be mediated by AT1 receptors, because acute treatment with losartan in rats chronically treated with ACE-I and chronic treatment with losartan lead to strong attenuation of TGF responses.

Key Words: renal circulation • renin-angiotensin system • microcirculation

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