The actions of azelnidipine, a dihydropyridine‐derivative Ca antagonist, on voltage‐dependent Ba²⁺ currents in guinea‐pig vascular smooth muscle

Background and purpose:

Although azelnidipine is used clinically to treat hypertension its effects on its target cells, Ca²⁺ channels, in smooth muscle have not been elucidated. Therefore, its effects on spontaneous contractions and voltage‐dependent L‐type Ca²⁺ channels were investigated in guinea‐pig portal vein.

Experimental approach:

The inhibitory potency of azelnidipine on spontaneous contractions in guinea‐pig portal vein was compared with those of other dihydropyridine (DHP)‐derived Ca antagonists (amlodipine and nifedipine) by recording tension. Also its effects on voltage‐dependent nifedipine‐sensitive inward Ba²⁺ currents (I_Ba) in smooth muscle cells dispersed from guinea‐pig portal vein were investigated by use of a conventional whole‐cell patch‐clamp technique.

Key results:

Spontaneous contractions in guinea‐pig portal vein were reduced by all of the Ca antagonists (azelnidipine, K_i=153 nM; amlodipine, K_i=16 nM; nifedipine, K_i=7 nM). In the whole‐cell experiments, azelnidipine inhibited the peak amplitude of I_Ba in a concentration‐ and voltage‐dependent manner (‐60 mV, K_i=282 nM; −90 mV, K_i=2 μM) and shifted the steady‐state inactivation curve of I_Ba to the left at −90 mV by 16 mV. The inhibitory effects of azelnidipine on I_Ba persisted after 7 min washout at −60 mV. In contrast, I_Ba gradually recovered after being inhibited by amlodipine, but did not return to control levels. Both azelnidipine and amlodipine caused a resting block of I_Ba at ‐90 mV. Only nifedipine appeared to interact competitively with S(‐)‐Bay K 8644.

Conclusions and implications:

These results suggest that azelnidipine induces long‐lasting vascular relaxation by inhibiting voltage‐dependent L‐type Ca²⁺ channels in vascular smooth muscle.

DOI: 10.1038/sj.bjp.0706919

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