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Nisoldipine‐induced relaxation in intact and skinned smooth muscles of rabbit coronary arteries
Author(s) -
Itoh T.,
Kanmura Y.,
Kuriyama H.,
Suzuki H.
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb10141.x
Subject(s) - nisoldipine , contraction (grammar) , depolarization , caffeine , chemistry , acetylcholine , tonic (physiology) , muscle contraction , biophysics , calcium , membrane potential , medicine , biology , biochemistry , nifedipine , organic chemistry
1 In smooth muscles of the rabbit coronary artery, nisoldipine inhibited the phasic and tonic responses of the contraction induced by 128 m m K (the IC 50 values were 4 × 10 −8 m and 1 × 10 −13 m , respectively). This agent also inhibited the tonic response of the acetylcholine (ACh) (10 −5 m )‐induced contraction (the IC 50 value was 3 × 10 −10 m ), but only slightly inhibited the phasic response (in 10 −7 m , 0.86 times the control). 2 Nisoldipine (<10 −7 m ) had no effect on the K‐induced depolarization of the membrane at any given concentration. This drug (5 × 10 −8 m ) did inhibit the oscillatory potential changes and spike potential evoked on the ACh‐induced slow depolarization. 3 After depletion of stored Ca from the polarized muscles (5.9 m m K), muscle cells accumulated Ca by application of 2.6 m m Ca without generation of contraction, i.e. a subsequently applied 20 m m caffeine produced the contraction in Ca‐free solution. Nisoldipine (<10 −7 m ) had little effect on this accumulation of Ca. 4 The rate of rise and time to reach the maximum amplitude of the 128 m m K‐ or ACh‐induced contraction (in 2.6 m m Ca) depended on the amount of stored Ca in cells. Nisoldipine (10 −8 m ) consistently inhibited the Ca‐induced contraction evoked in depolarized muscles (128 m m K), regardless of the amount of stored Ca. However, this agent (10 −8 m ) did not inhibit the Ca release from storage sites evoked by activation of the muscarinic receptor. 5 After prolonged superfusion (over 120 min) with Na‐ and Ca‐free solution (guanethidine and atropine were present), application of 2.6 m m Ca produced contraction which was inhibited by 10 −8 m nisoldipine, while the depolarization induced by application of these solutions was not inhibited by nisoldipine. 6 In saponin‐skinned muscles, nisoldipine had no effect on the contractile proteins, as estimated from the pCa‐tension relationship, or on the Ca accumulation into and Ca release from the Ca storage sites, as estimated from the caffeine‐induced contraction. 7 It is concluded that nisoldipine possesses a selective inhibitory action on voltage‐dependent Ca influx, when the Ca channel is activated by depolarization.