Abstract
The angiotensin type 1 (AT1) receptor antagonist, losartan (orally administered), decreases vasoconstrictor effects of angiotensin II (Ang II). Oral losartan is converted into the active metabolite, Exp3174, which causes most of the antagonistic effects. Effects of losartan as such have not been studied after its intra-arterial administration in humans. Therefore, we investigated the effects of both intra-arterially and orally administered losartan on AT1-receptor-mediated vasoconstriction. Forearm vascular resistance (FVR) was determined by venous occlusion plethysmography in 24 healthy subjects. Ang II (0.01, 0.1, 1.0, and 10.0 ng/kg/min) was infused into the brachial artery, before and after losartan, administered intra-arterially (dose range 100-3000 ng/kg/min) or orally (50 mg once daily for 5 days). Ang II concentration-dependently increased FVR (P < 0.05); tachyphylaxis did not occur. Losartan alone did not change FVR. Intra-arterially infused losartan dose-dependently inhibited Ang-II-induced vasoconstriction. At a concentration of 10(-8) M Ang II, losartan reduced FVR, as a percentage of baseline values, from 287 +/- 30 to 33 +/- 8% (mean +/- s.e.m.; P < 0.05). Orally given losartan reduced FVR from 297 +/- 40 to 73 +/...Continue Reading
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