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121.
Inhibition of nitric oxide synthase enhances contractile response of ventricular myocytes from streptozotocin-diabetic rats 总被引:1,自引:0,他引:1
The contractile hyporesponsiveness of the streptozotocin diabetic rat heart in vitro to β-adrenergic agonists is eliminated
when the heart is perfused with NG-nitro-l-arginine methyl ester (l-NAME), a non-selective inhibitor of nitric oxide synthase (NOS). The following study evaluated the hypothesis that an increased
production of NO/cGMP within the diabetic myocyte inhibits the β-adrenergic-stimulated increase in calcium current and contractile
response. Male Sprague-Dawley rats were given an intravenous injection of streptozotocin (60 mg/kg). After 8 weeks, L-type
calcium currents were recorded in ventricular myocytes using the whole cell voltage-clamp method. Shortening of isolated myocytes
was determined using a video edge detection system. cAMP and cGMP were measured using radioimmunoassay. Nitric oxide production
was determined using the Griess assay kit. Basal cGMP levels and nitric oxide production were elevated in diabetic myocytes.
Shortening of the diabetic myocytes in response to isoproterenol (1 μM) was markedly diminished. However, there was no detectable
difference in the isoproterenol-stimulated L-type calcium current or cAMP levels between control and diabetic myocytes. Acute
superfusion of the diabetic myocyte with l-NAME (1 mM) decreased basal cGMP and markedly enhanced the shortening response to isoproterenol but did not alter isoproterenol-stimulated
calcium current. These data suggest that increased production of NO/cGMP within the diabetic myocyte suppressed β-adrenergic
stimulated shortening of the myocyte. However, NO/cGMP apparently does not suppress shortening of the myocyte by inhibition
of the β-stimulated calcium current. 相似文献
122.
Rücker B Almeida ME Libermann TA Zerbini LF Wink MR Sarkis JJ 《Molecular and cellular biochemistry》2007,306(1-2):247-254
In the present study we investigate the biochemical properties of the members of NPP family in synaptosomes prepared from
rat heart left ventricles. Using p-nitrophenyl-5′-thymidine monophosphate (p-Nph-5′-TMP) as substrate for E-NPPs in rat cardiac synaptosomes, we observed an alkaline pH dependence, divalent cation dependence
and the K
M
value corresponded to 91.42 ± 13.97 μM and the maximal velocity (V
max
) value calculated was 63.79 ± 3.59 nmol p-nitrophenol released/min/mg of protein (mean ± SD, n = 4). Levamisole (1 mM), was ineffective as inhibitor of p-Nph-5′-TMP hydrolysis in pH 8.9 (optimum pH for the enzyme characterized). Suramin (0.25 mM) strongly reduced the hydrolysis
of p-Nph-5′-TMP by about 46%. Sodium azide (10 and 20 mM) and gadolinium chloride (0.3 and 0.5 mM), E-NTPases inhibitors, had
no effects on p-Nph-5′-TMP hydrolysis. RT-PCR analysis of left ventricle demonstrated the expression of NPP2 and NPP3 enzymes, but excluded
the presence of NPP1 member. By quantitative real-time PCR we identified the NPP3 as the enzyme with the highest expression
in rat left ventricle. The demonstration of the presence of the E-NPP family in cardiac system, suggest that these enzymes
could contribute with the fine-tuning control of the nucleotide levels at the nerve terminal endings of left ventricles that
are involved in several cardiac pathologies. 相似文献
123.
In the infarcted rat heart, the increase of NO occurs in the hypertrophied myocardium of non-infarcted areas and its antihypertrophic
efficacy has been well established. As another endogenous regulator and the reliable index of heart pathology, B-type natriuretic
peptide also exhibits the antihypertrophic properties in many tissues by elevating intracellular cGMP. Several studies indicate
that natriuretic peptides family may exert some actions in part via a nitric oxide pathway following receptor-mediated stimulation
of iNOS. Therefore, it raises our great interest to ask what role NO plays in the antihypertrophic actions of B-type natriuretic
peptide in cardiomyocytes. Incubation of cardiomyocytes under mild hypoxia for 12 h caused a significant increase in cellular
protein content, protein synthesis and cell surface sizes. This growth stimulation was suppressed by exogenous B-type natriuretic
peptide in a concentration dependent manner. Furthermore, the generation of intracellular cGMP, the upregulation of iNOS mRNA
expression, the increase of iNOS activity and subsequent nitrite generation in hypertrophic cardiomyocytes was also increased
by B-type natriuretic peptide. AG, a selective iNOS inhibitor, inhibited the upregulation of iNOS expression and the increase
of iNOS activity by the combination of B-type natriuretic peptide/mild hypoxia or by the combination of 8-bromo-cGMP/mild
hypoxia. Rp-8-br-cGMP, cGMP dependent protein kinase inhibitor, attenuated the actions of B-type natriuretic peptide and 8-bromo-cGMP
which increases intracellular cGMP independent of B-type natriuretic peptide. In conclusion, our present data suggest that
B-type natriuretic peptide exerted the antihypertrophic effects in cardiomyocytes, which was partially attributed to induction
of iNOS-derived NO by cGMP pathway. 相似文献
124.
Mubagwa K Gwanyanya A Zakharov S Macianskiene R 《Archives of biochemistry and biophysics》2007,458(1):73-89
Magnesium regulates various ion channels in many tissues, including those of the cardiovascular system. General mechanisms by which intracellular Mg(2+) (Mg(i)(2+)) regulates channels are presented. These involve either a direct interaction with the channel, or an indirect modification of channel function via other proteins, such as enzymes or G proteins, or via membrane surface charges and phospholipids. To provide an insight into the role of Mg(i)(2+) in the cardiovascular system, effects of Mg(i)(2+) on major channels in cardiac and smooth muscle cells and the underlying mechanisms are then reviewed. Although Mg(i)(2+) concentrations are known to be stable, conditions under which they may change exist, such as following stimulation of beta-adrenergic receptors and of insulin receptors, or during pathophysiological conditions such as ischemia, heart failure or hypertension. Modifications of cardiovascular electrical or mechanical function, possibly resulting in arrhythmias or hypertension, may result from such changes of Mg(i)(2+) and their effects on cation channels. 相似文献
125.
Tateishi K Ashihara E Honsho S Takehara N Nomura T Takahashi T Ueyama T Yamagishi M Yaku H Matsubara H Oh H 《Biochemical and biophysical research communications》2007,352(3):635-641
Recent evidence suggested that human cardiac stem cells (hCSCs) may have the clinical application for cardiac repair; however, their characteristics and the regulatory mechanisms of their growth have not been fully investigated. Here, we show the novel property of hCSCs with respect to their origin and tissue distribution in human heart, and demonstrate the signaling pathway that regulates their growth and survival. Telomerase-active hCSCs were predominantly present in the right atrium and outflow tract of the heart (infant > adult) and had a mesenchymal cell-like phenotype. These hCSCs expressed the embryonic stem cell markers and differentiated into cardiomyocytes to support cardiac function when transplanted them into ischemic myocardium. Inhibition of Akt pathway impaired the hCSC proliferation and induced apoptosis, whereas inhibition of glycogen synthase kinase-3 (GSK-3) enhanced their growth and survival. We conclude that hCSCs exhibit mesenchymal features and that Akt/GSK-3beta may be crucial modulators for hCSC maintenance in human heart. 相似文献
126.
Estradiol can act to protect against hippocampal damage resulting from transient global ischemia, but little is known about the functional consequences of such neuroprotection. The present study examines whether acute estradiol administered prior to the induction of transient global ischemia protects against hippocampal cell death and deficits in performance on a spatial learning task. Ovariectomized female rats were primed with estradiol benzoate or oil vehicle 48 and 24 h prior to experiencing one of three durations of 4-vessel occlusion (0, 5, or 10 min). Performance on the cued and hidden platform versions of the Morris water maze was assessed 1 week following ischemia. On the cued platform task, neither hormone treatment nor ischemia significantly influenced acquisition. When tested on the hidden platform task, however, oil-treated rats exhibited impairments in spatial learning after either 5 or 10 min of ischemia while estradiol-treated rats showed no impairments after 5 min of ischemia and only mild impairments after 10 min of ischemia. Immediately following behavioral testing, rats were perfused and survival of CA1 pyramidal cells was assessed. Ischemia was associated with the loss of CA1 pyramidal cells but rats that received estradiol prior to ischemia showed less severe damage. Furthermore, the extent of cell loss was correlated with degree of spatial bias expressed on a probe trial following hidden platform training. These findings indicate that acute exposure to estradiol prior to ischemia is both neuroprotective and functionally protective. 相似文献
127.
扩张型心肌病是一种以左心室和,或右心室扩大、心肌收缩功能受损为主要特征的心肌疾病,是除冠心病和高血压以外导致心力衰竭的主要病因之一。家族性扩张型心肌病约占扩张型心肌病的35%。目前为止,发现的和扩张型心肌病相关的基因突变主要是心肌蛋白基因突变和细胞骨架蛋白基因突变,此外还有线粒体DNA的突变和能量代谢相关的基因突变。本文对引起家族性扩张型心肌病的分子遗传进展进行了总结。 相似文献
128.
Background
Implantable Cardioverter-defibrillators (ICD) reduce mortality in survivors of cardiac arrest (CA). We investigated the predictors of mortality after ICD implantation in survivors of CA.Methods
Retrospective review of clinical records and social security death index of all patients who received an ICD in a preexisting database of survivors of CA at the University of Pittsburgh Medical Center was performed. Multivariate analyses using the Cox proportional hazard model were performed with backward elimination to identify independent predictors of the time to death, and Kaplan-Meier curves were plotted.Results
Eighty patients (64 men) with a mean age of 64.4±12.5 years were followed for 4.7±2.3 years after ICD implantation. Survival rates were 93.8%, 65% and 50% at 1, 5, and 10 years, respectively. Independent predictors of time to death were determined to include age (hazard ratio (HR) = 1.91 per 10-year increase, p = 0.003), serum creatinine ≥ 1.3 mg/dL (HR = 2.56, p = 0.004), and QRS width >120 ms (HR = 5.14, p = 0.012).Conclusions
In this sample of ICD recipients secondary to CA, older age, elevated serum creatinine, and wider QRS duration were independent predictors of mortality. The presence of more than one risk factor in the same patient was associated with higher mortality rates. Whether interventions such as biventricular pacing can offset this increase risk of death warrants further investigation. 相似文献129.
Rosman J Dhillon S Mayer A Hanon S Paul S 《Indian pacing and electrophysiology journal》2007,7(4):215-217
Background
Cardiac Resynchronization Therapy (CRT) is indicated for the treatment of advanced heart failure with severe systolic dysfunction and intraventricular conduction delay. Patient selection for this technology is vital, though it remains unclear which patients benefit most from CRT. We tested the hypothesis that patients with non-ischemic cardiomyopathy have a superior mortality benefit from CRT than ischemic cardiomyopathy patients.Methods
We evaluated 95 CRT patients to determine which factors predict mortality.Results
Patients with non-ischemic cardiomyopathy had a significantly better prognosis than patients with ischemic cardiomyopathy.Conclusion
Larger prospective studies can substantiate this finding and better delineate which patients benefit most from CRT. 相似文献130.
目的总结和分析同期施行冠状动脉搭桥和心脏瓣膜手术的体外循环方法。方法125例患者分为3组:M组(冠脉病变及二尖瓣病变)75例,A组(冠脉病变及主动脉瓣病变)34例,D组(冠脉病变及二尖瓣和主动脉瓣病变)16例。心肌保护采用4:1冷含血停搏液,应用单纯顺灌、顺灌逆灌结合、顺灌桥灌结合、顺逆灌和桥灌结合技术。结果术中转流平稳,血流动力学稳定,监测指标均在正常范围,无手术死亡。结论同期施行冠状动脉搭桥和心脏瓣膜手术,术中良好的心肌保护方法和合理的体外循环灌注是保证手术顺利成功的重要因素。 相似文献