当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide- and kinin-dependent mechanism.

Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide- and kinin-dependent mechanism.

Abstract：

:1. We investigated the nitric oxide (NO) dependence of vasorelaxation in response to different calcium channel blockers (CCB), in rabbit femoral artery in vivo. 2. Anaesthetized rabbits underwent femoral artery ligation, and blood from the proximal artery was returned distal to the ligature through a constant infusion pump. The effects of local injection of CCB on perfusion pressure and plasma nitrite+nitrate (NO(x), which reflects local NO biosynthesis) concentration in this system were determined. 3. Intra-arterial verapamil, nifedipine or amlodipine 10 micromol x kg(-1) each reduced perfusion pressure. Pre-treatment with intra-arterial N(G)-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor) 1 micromol x kg(-1) did not affect responses to verapamil or nifedipine, but attenuated the reduction in perfusion pressure to amlodipine, from 33.2+/-2.1% to 22.5+/-1.6% (P=0.002). 4. Intra-arterial amlodipine--unlike verapamil or nifedipine--increased femoral venous NO(x), from 9.1+/-0.4 microM to 14.1+/-0.5 microM (P=0.005). 5. The bradykinin B2 receptor antagonist HOE 140, 30 mg x kg(-1), attenuated the reduction in perfusion pressure and abolished the rise in venous NO(x) concentration, following intra-arterial amlodipine. 6. Amlodipine potently inhibited serum angiotensin converting-enzyme (ACE) activity in vitro, as effectively as enalapril at similar concentrations. 7. These results suggest that the vasorelaxant effects of nifedipine and verapamil are NO-independent, whereas those of amlodipine are partly NO-dependent, in rabbit femoral artery in vivo. This effect of amlodipine occurs through B2 receptor activation, and may be related to an increase in local bradykinin through inhibition of ACE.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Xu B,Xiao-hong L,Lin G,Queen L,Ferro A

doi

10.1038/sj.bjp.0704753

subject

Has Abstract

pub_date

2002-06-01 00:00:00

pages

375-82

issue

3

eissn

0007-1188

issn

1476-5381

journal_volume

136

pub_type

杂志文章

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