Normal TGF responsiveness during chronic treatment with angiotensin-converting enzyme inhibition - Role of AT1 receptors

Acute inhibition of angiotensin II formation by angiotensin-converting enzy me inhibition (ACE-I) attenuates tubuloglomerular feedback (TGF) responsive ness. This has been proposed to facilitate sodium excretion, which contribu tes to the antihypertensive effects of ACE-I. However, in previous experime nts in spontaneously hypertensive Fawn-hooded rats, TGF responses were norm al during chronic ACE-I treatment. In the present study, we investigated TG F:responsiveness during chronic ACE-I treatment in normotensive rats and th e involvement of changes in nitric oxide or angiotensin II activity. Maximu m TGF responses were assessed in control Sprague-Dawley rats and in rats ac utely (acute ACE-1,3 mug/min IV) and chronically (chronic ACE-I, 100 mg/L P O 2 to 3 weeks + acute 3 mug/min enalaprilat IV) treated with ACE-I. In all groups, TGF responses were also assessed during late proximal tubular perf usion with 1 mmol/L nitro-L-arginine. In a last group, the chronic ACE-I tr eatment was combined with acute ACE-I and high doses of intrarenal losartan (acute 3 mug/min enalaprilat IV + 50 mg/kg losartan). The maximum TGF resp onses in acutely treated ACE-I rats were strongly attenuated (0.7 +/- 0.4 m m Hg versus 6.5 +/- 0.8 mm Hg in control rats, P < 0.05), Mean arterial pre ssure was lower in the chronically treated ACE-I group (107 + 5 mm Hg versu s 126 +/- 5 mm Hg in control rats, P < 0.05); however, TGF responses were n ormal (6.4 +/- 0.9 mm Hg). Intraluminal nitro-L-arginine infusion did not i nfluence TGF responses during acute ACE-I (2.31 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 wi th ACE-I with superimposed acute infusion of losartan or chronically treate d with losartan, TGF responses were significantly attenuated (1.8 +/- 0.8 m m 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 TG F responses. This phenomenon appears to be mediated by AT1 receptors, becau se acute treatment with losartan in rats chronically treated with ACE-I and chronic treatment with losartan lead to strong attenuation of TGF response s.