| Endogenous opiod peptides and opiod receptors, which is widespreadly existing in diverse systems, play important roles in central analgesia as well as in the regulation of cardiovascular functions. Rich opiod receptors are found existing in the membrane of cardiac myocytes and in blood vessel wall. The cells in the heart are capable of producing EOP, suggesting opiod peptides act on the cardiovascular system. Since EOP and opiod receptors are deeply involved in the regulation of many peripheral organs and in the initiation and development of heart diseases, the researches on them are significant both in physiology and in pathology.Three subtypes, μ, δ and κ , of opiod receptors exist in the heart, in which the κ subtype is dominant. Lots of previous researches already reported that, activation of the opiod receptors induces such physiological effects like the decrease in the contractility of cardiac myocytes and the dilation of blood vessels, they are also involved in the pathological processes like arrathemia and the reperfusion after ischemia.Sympathetic-catecolamine system is indispensable in themaintaining of the function of the heart and the homeostasis of blood pressure. Moreover, adjustment of the corresponding receptors and their intracellular effectiveness may cause many cardiovascular diseases, including hypertension , anginapectoris, arrhythmia, heart failure and so on. It was already discovered that opiod peptides not only co-exist with non-adrenaline in the sympathetic terminals, but also regulate the adrenergic control on cardiac function as well.U50,488H, a specific K receptor agonist, were found to down-regulate both the contractile function of the heart and the increment in contractility induced by B receptor agonist in vivo. Since the contraction of the cardiac myocytes are closely related to the calcium influx and to the calcium homeostasis, it is inferred that U50,488H regulates the intracellular calcium and this is testified.In the present study, the effects of U50,488H on the contractility, the concentration of intracellular calcium, and the property of L-type calcium channels of single myocytes were investigated, the inter-relations between opiod receptor and 3 receptor before and after hypoxia were determind as well.1.Objectives of the work(1) To observe the action of U50,488H on the contractile amplitude of single rat cardiac myocytes.(2) To observe the effects of U50,488H on the calcium transient in rat ventricular myocytes.(3) To observe the effects of U50,488H on the L-type calcium channels in rat ventricular myocytes.(4) To study the interaction between opiod receptor and P receptor in normal rat ventricular myocytes.(5) To investigate the changes and mechanisms of the interaction between opiod receptor and P receptor in rat ventricular myocytes subjected to hypoxia.2. Methods of the work(1) Rat ventricular myocytes were isolated by conventionalenzyme action, hypoxia of the cell was produced by continuously bubbling nitrogen gas.(2)IonOptix moving edges detection system was employed in the recording of the contraction and calcium transient in single cells.(3) Whole-cell patch clamp technique was used to observe L-type calcium current.3. Main results of the work(1)U50,488H (100 nmol/L-100 umol/L) reduced the contractile amplitude of the myocytes in a dose-dependent manner (P<0.01, compared with control) and this effect of reduction was blocked by both Nor-BNI, a specific K receptor blocker and PTX, a Gi protein inhibitor. Iso (1 nmol/L-1 umol/L) increased the amplitude of the single cell contraction evoked by electric stimulation, also in a dose-dependent way, while this effect of augmentation was inhibited by U50,488H(P<0.01, compared with control).(2) U50,488H ( 100 nmol/L-100 umol/L ) dose-dependently reduced the amplitude of calcium transient in cardiac myocytes (P<0.01, compared with control) and this effect of was also blocked by either nor-BNI or PTX...
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