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Influence of losartan on alpha-adrenoceptor-mediated vasoconstrictor response in humans
K Harada1, A Kawaguchi, M Ohmori
1Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan. kahikeko@jichi.ac.jp
To evaluate the influence of losartan on alpha-adrenoceptor-mediated vasoconstrictor response, we examined dorsal hand vein constrictor response to phenylephrine (16-8,192 ng/min) and fingertip vasoconstrictor response to cold stimulation with and without pretreatment with losartan (50 mg/day) for 3 days in nine healthy men. The effect of coadministration of angiotensin II (Ang II) (0.3 ng/min) on the venoconstrictor response also was evaluated. Oral pretreatment with losartan alone influenced neither of the responses. The log of the infusion rate of phenylephrine producing half-maximal venoconstriction [log(ED50)] was 2.69 +/- 0.10 (mean +/- SEM) for control and 2.68 +/- 0.09 for losartan, and the reduction ratio of fingertip blood flow was 68.1 +/- 4.0% for control and 66.7 +/- 4.3% for losartan. Coadministration of Ang II, however, significantly enhanced the venoconstrictor response to phenylephrine [log(ED50): 2.43 +/- 0.09, p < 0.05 vs. control], and the pretreatment with losartan attenuated this effect [log(ED50): 2.60 +/- 0.11]. These findings indicate that the alpha-adrenoceptor-mediated vasoconstrictor response is not influenced by losartan; however, it is enhanced by exogenous Ang II, and losartan attenuates the enhanced response, in healthy human subjects.
To evaluate the influence of losartan on alpha-adrenoceptor-mediated vasoconstrictor response, we examined dorsal hand vein constrictor response to phenylephrine (16-8,192 ng/min) and fingertip vasoconstrictor response to cold stimulation with and without pretreatment with losartan (50 mg/day) for 3 days in nine healthy men. The effect of coadministration of angiotensin II (Ang II) (0.3 ng/min) on the venoconstrictor response also was evaluated. Oral pretreatment with losartan alone influenced neither of the responses. The log of the infusion rate of phenylephrine producing half-maximal venoconstriction [log(ED50)] was 2.69 +/- 0.10 (mean +/- SEM) for control and 2.68 +/- 0.09 for losartan, and the reduction ratio of fingertip blood flow was 68.1 +/- 4.0% for control and 66.7 +/- 4.3% for losartan. Coadministration of Ang II, however, significantly enhanced the venoconstrictor response to phenylephrine [log(ED50): 2.43 +/- 0.09, p < 0.05 vs. control], and the pretreatment with losartan attenuated this effect [log(ED50): 2.60 +/- 0.11]. These findings indicate that the alpha-adrenoceptor-mediated vasoconstrictor response is not influenced by losartan; however, it is enhanced by exogenous Ang II, and losartan attenuates the enhanced response, in healthy human subjects.