Losartan and captopril follow different mechanisms to decrease pressor responses in the pithed rat

Hitomi Yokoyama, Shinya Minatoguchi, Masatoshi Koshiji, Yoshihiro Uno, Masao Kakami, Chisato Nagata, Hiroyasu Ito, Hisayoshi Fujiwara

研究成果: ジャーナルへの寄稿学術論文査読

7 被引用数 (Scopus)

抄録

1. We investigated the effects of losartan and captopril on noradrenaline (NA) release and vascular reactivity to NA in the pithed rat. 2. The presser responses to sympathetic nerve stimulation (SNS) before and after i.v. administration of captopril (1 mg/kg), losartan (1 and 10 mg/kg), sodium nitroprusside (SNP; 5 μg/kg per min), losartan (1 mg/kg) + captopril (1 mg/kg), captopril (1 mg/kg) + losartan (1 mg/kg) or the bradykinin B2 receptor antagonist HOE 140 (1 mg/kg) + captopril (1 mg/kg) were measured. Plasma NA concentrations were measured during 60 s SNS before and after losartan (1 mg/kg), captopril (1 mg/kg), SNP (5 μg/kg per min) or HOE 140 (1 mg/kg) + captopril (1mg/kg). Presser responses to exogenous NA were measured before and after administration of losartan (1 mg/kg), captopril (1 mg/kg), HOE 140 (1 mg/kg) + captopril (1 mg/kg) or the nitric oxide synthase (NO) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) + captopril (1 mg/kg). 3. Captopril, losartan and SNP decreased frequency-response curves to a similar extent. The captopril-induced decrease in presser responses to SNS was restored by pretreatment with HOE 140. Adding captopril to losartan decreased the curve more than did adding losartan to captopril. Both losartan, captopril and HOE 140 + captopril significantly decreased the plasma NA concentration after SNS (34.1 ± 5.0, 27.4 ± 2.6 and 41.4 ± 8.1%, respectively). Sodium nitroprusside did not change the plasma NA concentration after SNS (3.8 ± 28.2%). The dose-response curves to i.v. NA were not affected by losartan, but were significantly decreased by captopril. However, responses to NA that were reduced by captopril were restored to control values by pretreatment with HOE 140 or L-NAME. 4. We suggest that both losartan and captopril decrease presser responses to SNS by inhibiting NA release from sympathetic nerve endings; however, captopril also decreases 'vascular reactivity' to NA, which is mediated by nitric oxide produced by activation of the bradykinin B2 receptors.

本文言語英語
ページ(範囲)697-705
ページ数9
ジャーナルClinical and Experimental Pharmacology and Physiology
24
9-10
DOI
出版ステータス出版済み - 1997
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生理学
  • 薬理学
  • 生理学(医学)

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