Kelm M, Feelisch M, Krebber T, Motz W, Strauer B E
Department of Cardiology, Heinrich-Heine-University, Düsseldorf, FRG.
J Vasc Res. 1993 May-Jun;30(3):132-8. doi: 10.1159/000158987.
Although the content of histamine in myocardial tissue is high, its contribution to the regulation of coronary blood flow has not been clearly defined. The aim of the present study was to investigate whether or not nitric oxide (NO), an important modulator of coronary vascular tone, is involved in histamine-induced coronary vasomotion and to characterize which histaminergic receptor subtype mediates this process. Isolated, constant-flow-perfused guinea pig hearts were challenged with histamine, the H1-receptor agonist pyridylethylamine (PYR) and the H2-receptor agonist dimaprit (DIM). Apart from coronary perfusion pressure (CPP), left ventricular pressure (LVP) and the development of contractile force (dp/dt), the release of NO and cyclic GMP (cGMP) were continuously measured. Histamine and DIM induced concentration dependently a coronary vasodilatation with an almost 50% decrease in CPP paralleled by an enhancement of LVP and dp/dt by more than 80%. PYR selectively reduced CPP by 47% without affecting LVP and dp/dt. Histamine- and PYR-induced coronary vasodilatation were paralleled by a more-than-twofold increase in basal cGMP release from isolated hearts, whereas DIM exerted no effects on cGMP release. Oxyhemoglobin (4 microM), an effective scavenger of NO, shifted the concentration-response curve for histamine- and PYR-induced changes in CPP significantly to the right and in parallel inhibited the increase in cGMP release. Histamine and PYR rapidly (within 2 s) decreased CPP, while the onset of DIM-induced coronary vasodilatation followed changes in LVP with a lag period of 10 s. Histamine increased basal NO release concentration dependently by a maximum of 351 +/- 21 pmol/min.(ABSTRACT TRUNCATED AT 250 WORDS)
虽然心肌组织中的组胺含量很高，但其对冠状动脉血流调节的作用尚未明确界定。本研究的目的是调查一氧化氮（NO），一种冠状动脉血管张力的重要调节因子，是否参与组胺诱导的冠状动脉血管运动，并确定哪种组胺能受体亚型介导这一过程。用组胺、H1受体激动剂吡啶乙胺（PYR）和H2受体激动剂二甲双胍（DIM）刺激离体的、恒流灌注的豚鼠心脏。除了冠状动脉灌注压（CPP）、左心室压力（LVP）和收缩力的发展（dp/dt）外，还连续测量NO和环磷酸鸟苷（cGMP）的释放。组胺和DIM浓度依赖性地诱导冠状动脉舒张，CPP降低近50%，同时LVP和dp/dt增强超过80%。PYR选择性地使CPP降低47%，而不影响LVP和dp/dt。组胺和PYR诱导的冠状动脉舒张伴随着离体心脏基础cGMP释放增加两倍以上，而DIM对cGMP释放无影响。氧合血红蛋白（4 microM），一种有效的NO清除剂，使组胺和PYR诱导的CPP变化的浓度-反应曲线显著右移，并同时抑制cGMP释放的增加。组胺和PYR迅速（2秒内）降低CPP，而DIM诱导的冠状动脉舒张的起始跟随LVP的变化，有10秒的延迟期。组胺浓度依赖性地增加基础NO释放，最大增加量为351±21 pmol/min。（摘要截断于250字）
