Influence of losartan on alpha-adrenoceptor-mediated vasoconstrictor response in humans.
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.
Harada
K
K
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan. kahikeko@jichi.ac.jp
Kawaguchi
A
A
Ohmori
M
M
Fujimura
A
A
D000328:Adult; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D005385:Fingers / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine; D019808:Losartan