| The natriuretic peptides(NPs) are a family of vasoactive polypeptides possessing natriuretic diuretic and vasodilative actions. Recently, increasing attention has been paid to their inhibitory effects on cardiac hypertrophy and vascular remodeling in both basic research and clinical application. And some research reported that the ANP and CNP have the negative inotropic effects. Vasonatrin peptide (VNP) is a man-made new member of natriuretic peptide family. Previous studies have demonstrated that VNP was effective in preventing and treating hypoxic pulmonary hypertension and right ventricular hypertrophy. But the authors have not performed any experimental study to determine the effects of VNP on the twitch amplitude of cardiac myocytes. Arrhythmia is often concomitant of CHF so whether VNP regulates the permeability of cardiomyocyte ion needs to be investigated.The antiadrenergic action of NPs is expressed as a reduction in the Iso-induced enhancement of ventricular contractility, cardiomyocyte shortening, the magnitude of the calcium ions inward current and action potential duration and amplitude, and phosphorylation of various cellular proteins thought to be associated with contractile function.It is well accepted that the transient elevation of intracellular Ca2+ concentration ([Ca2+]i) is required for excitation-contraction coupling in the ventricular myocyte. The voltage-sensitive Ca2+ current is thought to initiate the generation of these transients, contributing to the elevation of [Ca2+]i and serving as a stimulus triggering the release of Ca2+ from the sarcoplasmic reticulum (SR). The transient increase in [Ca2+]i results in myocyte contraction. Activation of P -adrenergic receptors by Iso greatly increases the contractile activity of the myocardium, In part, by increasing the influx of Ca2+ through Ca2+ channels and enhancing the magnitude, and shortening the duration, of Ca2+ transients in ventricular myocytes. These effects are thought to result from the Iso-induced activation of adenylyl cyclase (AC), resulting in the phosphorylation by cAMP-dependent protein kinase of the Ca2+ channel and proteins associated with contractile responses.In the present study, we investigated the effects of VNP on the twitch amplitude, intracellular calcium transient, L-type calciumcurrent and the sodium current of the rat ventricular myocytes.1.Aims(1) To investigate the effects of Iso on the [Ca2+]i transient and twitch amplitude in the rat cardiomyocytes and underlying cell signal transductant mechanisms of VNP on the regulation of contractility.(2)To investigate the effects of VNP on Ica L and INaand reveal its mechanisms, so as to extend the research and use fields of VNP.(3)Iso may induce and accelerate much of cardiovascular diseases, so the effects which antagnoists its activation may provide potential protection and treatment of these dieases. NPs possesses these ability, so we investigated the effects of VNP, which may provide foundation to animal experiment, and then provide the potential for theapplication of VNP in the clinic. 2.Methods(l)Ventricular myocytes were isolated with a collagenase perfusion method. The calcium tolerant cells were obtained by the extracellular Ca2+ concentration increased gradually after isolation.(2)Measurement of myocyte twitch amplitude and calcium transient were performed using an optical video system. In order to understand the effects of VNP on the twitch amplitude, [Ca2+]i transient, and underlying intracellular signaling mechanism. We observed the effects of VNP on Iso-enhanced twitch amplitude and calcium transient, and in the presence of 8-Br-cGMP, HS-142-1 and MB.(3) The optical video system was also used to measure the twitch amplitude and calcium transient in the single myocytes. In order to elucidate the role of VNP in beta-receptor mediated signaling transduction, We determined the effects of VNP on twitch amplitude, calcium transient and production of cAMP, in the presence of iso, a beta-receptor agonist,and cholera tox...
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