Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide‐ and kinin‐dependent mechanism
- 1 June 2002
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 136 (3), 375-382
- https://doi.org/10.1038/sj.bjp.0704753
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.Keywords
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