TY - JOUR
T1 - Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide- and kinin-dependent mechanism
AU - Xu, B
AU - Xiao-hong, L
AU - Lin, G
AU - Queen, L
AU - Ferro, A
PY - 2002
Y1 - 2002
N2 - 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 (NOx, which reflects local NO biosynthesis) concentration in this system were determined. 3. Intra-arterial verapamil, nifedipine or amlodipine 10 [mu]mol kg-1 each reduced perfusion pressure. Pre-treatment with intra-arterial NG-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor) 1 [mu]mol 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 NOx, from 9.1+/-0.4 [mu]M to 14.1 +/-0.5 [mu]M (P=0.005). 5. The bradykinin B2 receptor antagonist HOE 140, 30 mg kg-1, attenuated the reduction in perfusion pressure and abolished the rise in venous NOx 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
AB - 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 (NOx, which reflects local NO biosynthesis) concentration in this system were determined. 3. Intra-arterial verapamil, nifedipine or amlodipine 10 [mu]mol kg-1 each reduced perfusion pressure. Pre-treatment with intra-arterial NG-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor) 1 [mu]mol 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 NOx, from 9.1+/-0.4 [mu]M to 14.1 +/-0.5 [mu]M (P=0.005). 5. The bradykinin B2 receptor antagonist HOE 140, 30 mg kg-1, attenuated the reduction in perfusion pressure and abolished the rise in venous NOx 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
UR - http://www.scopus.com/inward/record.url?scp=0036016107&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0704753
DO - 10.1038/sj.bjp.0704753
M3 - Article
SN - 1476-5381
VL - 136
SP - 375
EP - 382
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 3
ER -