Effects Of Calcium Channel Blockers On Histamine-induced Contracion Of Isolated Coronary Arteries

OBJECTIVE The study was designed to compare the effects of nifedipine, nimodipine, verapamil, diltiazm on the histamine-induced contraction of isolated pig coronary arteries and mechanism. METHODS The preparation of pig isolated coronary artery strips. The artery strips were suspended from tension energy transducer (JH-2,Beijing) and were observed with MS2000 computer system. The dose-response curves of histamine were done in the condition of without calcium antagonists or low concentration or secondary concentration or high concentration calcium antagonists. The result of maximum contractile response induced by 10-3 mol/l histamine was regarded as 100%. Then we calculate the percentage of contractile response induced by histamine of each concentration. RESULT 1,Coronary artery began to contract by10-6 mol/l histamine. The peak of contraction induced by 10-3 mol/l histamine. Histamine induced concentration-dependent increase in tone of coronary artery smooth muscle. 2,Four calcium antagonists inhibited the contraction role of left coronary artery induced by histamine. Pretreatment with 10-8,10-7,10-6mol/l nifedipine produced the role that inhibited the vasoconstriction induced by 10-3 mol/l histamine were 49.0±6.7,22.1%±5.1%,15.4%±3.7% of matched control respectively. Pretreatment with 10-8,10-7,10-6mol/l nimodipine produced the role that inhibited the vasoconstriction induced by histamine were 64.9±9.8,37.7%±9.8%,24.0%±7.8% of matched control respectively. Pretreatment with 10-7mol/l,10-6mol/l,10-5mol/l verapamil produced the role that inhibited the vasoconstriction induced by histamine were 81.6%±8.6%,43.6%±7.3%,24.1%±16.4% of matched control respectively. Pretreatment with 10-7mol/l,10-6mol/l,10-5mol/l diltiazem produced the role that inhibited the vasoconstriction induced by histamine were 90.2%±3.6%,59.1%±7.1%,45.5%±10.3% of matched control respectively.The PD2'values of nifedipine, nimodipine, verapamil, diltiazem were 8.12±0.28,7.33±0.46,5.92±0.45,5.37±0.41. 3. Four calcium antagonists inhibited the contraction role of right coronary artery induced by histamine. Pretreatment with 10-8,10-7,10-6mol/l nifedipine produced the role that inhibited the vasoconstriction induced by 10-3 mol/l histamine were 47.6±7.5,22.2%±5.3%,16.1%±5.2% of matched control respectively. Pretreatment with 10-8,10-7,10-6mol/l nimodipine produced the role that inhibited the vasoconstriction induced by histamine were 64.7±10.9%,38.2%±9.1%,22.6%±8.0% of matched control respectively. Pretreatment with 10-7mol/l,10-6mol/l,10-5mol/l verapamil produced the role that inhibited the vasoconstriction induced by histamine were 80.0%±8.6%,44.1%±7.1%,22.1%±2.9% of matched control respectively. Pretreatment with 10-7mol/l,10-6mol/l,10-5mol/l diltiazem produced the role that inhibited the vasoconstriction induced by histamine were 89.3%±3.7%,58.6%±6.3%,44.1%±9.2% of control respectively. The PD2'values of nifedipine, nimodipine, verapamil, diltiazem were 8.17±0.32, 7.33±0.48, 5.97±0.40,5.28±0.34. CONCLUSION Histamine could induced concentration-dependent increase in coronary artery tone. Histamine-induced contraction of coronary artery did not show transparent difference of locus.Histamine could contract coronary artery to a plateau type quickly and transiently. The subsequent sustained inferior contraction could maintain some time. The mechanism was as follow. In the presence of extracellular ca2+ ,histamine induced an elevation of cytosolic ca2+ concentrations of a peak and plateau type. Four calcium antagonist inhibited noncompetitively the effect that histamine induced the coronary artery contraction. The effect of dihydropyridine calcium antagonist was stonger than verapamil and diltiazem significantly by PD2'values. The inhibitory effects of ca2+ antagonist on the histamine-induced contraction or spasm of coronary artery may relate to their drug property.