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Snyder VL Turner M Li PK El-Sharkawy A Dunphy G Ely DL 《The Journal of steroid biochemistry and molecular biology》2000,73(5):251-256
The objective of this study was to examine the response of tissue steroid sulfatase (STS) levels in hypertensive rat strains, when blood pressure (BP) was lowered by different techniques at an early age. A 4×3 factoral design was used, in which males (n=6–8) from four rat strains (WKY, SHR, SHR/a, SHR/y) at 4 weeks of age, were randomly assigned to one of three treatment groups: a hydralazine group, a castration group and a control group. BP was measured by the tail cuff technique and verified by tail catheter at the end of the experiment. BP was significantly reduced by both treatments in the hypertensive strains (SHR, SHR/a, SHR/y) compared to respective control groups. At 15–17 weeks of age, animals were euthanized and heart, kidney, adrenal glands and liver were assayed for STS levels. The major trend in tissue STS was that castration significantly lowered: adrenal, heart and liver STS in specific strains. In conclusion, castration and hydralazine significantly lowered the BP in the hypertensive rat strains, but only castration consistently lowered STS levels across strains implicating testosterone as a regulator of tissue STS. 相似文献
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Raul A. Dulce Omer Yiginer Daniel R. Gonzalez Garrett Goss Ning Feng Meizi Zheng Joshua M. Hare 《The Journal of biological chemistry》2013,288(9):6522-6533
Although the combined use of hydralazine and isosorbide dinitrate confers important clinical benefits in patients with heart failure, the underlying mechanism of action is still controversial. We used two models of nitroso-redox imbalance, neuronal NO synthase-deficient (NOS1−/−) mice and spontaneously hypertensive heart failure rats, to test the hypothesis that hydralazine (HYD) alone or in combination with nitroglycerin (NTG) or isosorbide dinitrate restores Ca2+ cycling and contractile performance and controls superoxide production in isolated cardiomyocytes. The response to increased pacing frequency was depressed in NOS1−/− compared with wild type myocytes. Both sarcomere length shortening and intracellular Ca2+ transient (Δ[Ca2+]i) responses in NOS1−/− cardiomyocytes were augmented by HYD in a dose-dependent manner. NTG alone did not affect myocyte shortening but reduced Δ[Ca2+]i across the range of pacing frequencies and increased myofilament Ca2+ sensitivity thereby enhancing contractile efficiency. Similar results were seen in failing myocytes from the heart failure rat model. HYD alone or in combination with NTG reduced sarcoplasmic reticulum (SR) leak, improved SR Ca2+ reuptake, and restored SR Ca2+ content. HYD and NTG at low concentrations (1 μm), scavenged superoxide in isolated cardiomyocytes, whereas in cardiac homogenates, NTG inhibited xanthine oxidoreductase activity and scavenged NADPH oxidase-dependent superoxide more efficiently than HYD. Together, these results revealed that by reducing SR Ca2+ leak, HYD improves Ca2+ cycling and contractility impaired by nitroso-redox imbalance, and NTG enhanced contractile efficiency, restoring cardiac excitation-contraction coupling. 相似文献
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Daiber A Oelze M Coldewey M Kaiser K Huth C Schildknecht S Bachschmid M Nazirisadeh Y Ullrich V Mülsch A Münzel T Tsilimingas N 《Biochemical and biophysical research communications》2005,338(4):1865-1874
The hemodynamic and anti-ischemic effects of nitroglycerin (GTN) are rapidly blunted as a result of the development of nitrate tolerance. Hydralazine has been shown to prevent tolerance in experimental and clinical studies, all of which may be at least in part secondary to antioxidant properties of this compound. The antioxidant effects of hydralazine were tested in cell free systems, cultured smooth muscle cells, isolated mitochondria, and isolated vessels. Inhibitory effects on the formation of superoxide and/or peroxynitrite formation were tested using lucigenin and L-012 enhanced chemiluminescence as well as DHE-fluorescence. The peroxynitrite scavenging properties were also assessed by inhibition of nitration of phenol. Prevention of impairment of NO downstream signaling and GTN bioactivation was determined by measurement of P-VASP (surrogate parameter for the activity of the cGMP-dependent kinase-I, cGK-I) and mitochondrial aldehyde dehydrogenase (ALDH-2) activity. Hydralazine dose-dependently decreased the chemiluminescence signal induced by peroxynitrite from SIN-1 and by superoxide from HX/XO in a cell free system, by superoxide in smooth muscle cells and mitochondria acutely challenged with GTN. Moreover, hydralazine inhibited the peroxynitrite-mediated nitration of phenols as well as proteins in smooth muscle cells in a dose-dependent fashion. Finally, hydralazine normalized impaired cGK-I activity as well as impaired vascular ALDH-2 activity. Our results indicate that hydralazine is a highly potent radical scavenger. Thus, the combination with isosorbide dinitrate (ISDN) will favorably influence the nitroso-redox balance in the cardiovascular system in patients with congestive heart failure and may explain at least in part the improvement of prognosis in patients with chronic congestive heart failure. 相似文献
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目的:探讨肼苯哒嗪对疝修补术后患者慢性疼痛发生率的影响。方法:选择单侧腹股沟疝患者48人,随机分为实验组(T组)和对照组(c组)各24例,在术前3天至术后4天共7天内接受药物或安慰荆治疗。其中T组每日两次,每次10mg肼苯哒嗪,C组同样方式给予安慰剂。测量患者术后4天内的平均动脉)Z(MAP)、心率(HR)、NRS急性疼痛评分以及术后3月、6月S—LANSS慢性疼痛评分。结果:T组患者术后MAP明显低于C组(P〈0.05),HR两组相比无差异(P〉0.05);两组患者术后急性疼痛程度相比无统计学差别(P〉0.05);T组患者在术后3月和6月慢性疼痛发生率明显低于C组(P〈0.05)。结论:常规剂量肼苯哒嗪可以用于术后患者,对疝修补术后急性疼痛无影响,但可以明显降低术后慢性疼痛的发生率。 相似文献
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目的:探讨肼苯哒嗪对疝修补术后患者慢性疼痛发生率的影响。方法:选择单侧腹股沟疝患者48人,随机分为实验组(T组)和对照组(C组)各24例,在术前3天至术后4天共7天内接受药物或安慰剂治疗。其中T组每日两次,每次10mg肼苯哒嗪,C组同样方式给予安慰剂。测量患者术后4天内的平均动脉压(MAP)、心率(HR)、NRS急性疼痛评分以及术后3月、6月S-LANSS慢性疼痛评分。结果:T组患者术后MAP明显低于C组(P<0.05),HR两组相比无差异(P>0.05);两组患者术后急性疼痛程度相比无统计学差别(P>0.05);T组患者在术后3月和6月慢性疼痛发生率明显低于C组(P<0.05)。结论:常规剂量肼苯哒嗪可以用于术后患者,对疝修补术后急性疼痛无影响,但可以明显降低术后慢性疼痛的发生率。 相似文献
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