作者: Jeong, Lacey S ; Chandler, Selena ; Hakobyan, Tatevik ; Shockling, Lindsay ; Kimball, Kelly ; Hoff, Ellianna ; Chen, Yeong-Renn ; Kegecik, Karlina ; Srivastava, Geetika ; Kolz, Christopher ; Kang, Patrick T ; Pucci, Thomas ; Jabir, Abdur Rahman ; Dong, Feng ; Ohanyan, Vahagn ; Jia, Zhenyu ; Joshi, Hirva ; Shabani, Parisa ; Chilian, William M ; Chen, Chwen-Lih ; Sisakian, Hamayak ; Yin, Liya

AbstractBackground and aimsTakotsubo syndrome (TTS) is a conundrum without consensus about the cause. In a murine model of coronary microvascular dysfunction (CMD), abnormalities in myocardial perfusion played a key role in the development of TTS.Methods and resultsVascular Kv1.5 channels connect coronary blood flow to myocardial metabolism and their deletion mimics the phenotype of CMD. To determine if TTS is related to CMD, wild-type (WT), Kv1.5−/−, and TgKv1.5−/− (Kv1.5−/− with smooth muscle-specific expression Kv1.5 channels) mice were studied following transaortic constriction (TAC). Measurements of left ventricular (LV) fractional shortening (FS) in base and apex, and myocardial blood flow (MBF) were completed with standard and contrast echocardiography. Ribonucleic Acid deep sequencing was performed on LV apex and base from WT and Kv1.5−/− (control and TAC). Changes in gene expression were confirmed by real-time-polymerase chain reaction. MBF was increased with chromonar or by smooth muscle expression of Kv1.5 channels in the TgKv1.5−/−. TAC-induced systolic apical ballooning in Kv1.5−/−, shown as negative FS (P < 0.05 vs. base), which was not observed in WT, Kv1.5−/− with chromonar, or TgKv1.5−/−. Following TAC in Kv1.5−/−, MBF was lower in LV apex than in base. Increasing MBF with either chromonar or in TgKv1.5−/− normalized perfusion and function between LV apex and base (P = NS). Some genetic changes during TTS were reversed by chromonar, suggesting these were independent of TAC and more related to TTS.ConclusionAbnormalities in flow regulation between the LV apex and base cause TTS. When perfusion is normalized between the two regions, normal ventricular function is restored.

2001-09-01·American Journal of Physiology-Heart and Circulatory Physiology2区 · 医学

Effect of estrogen replacement therapy on distribution of myocardial blood flow in female anesthetized rabbits

2区 · 医学

Article

作者: Kingma, J. G. ; Rouleau, J. R. ; Blouin, A. ; Lavallée, B. ; Bélanger, A. ; Dagnault, A. ; Simard, D.

Estrogen replacement therapy reduces risk of cardiovascular events by altering coronary vasoregulation and distribution of blood flow. Vessel reactivity and blood flow distribution were assessed in anesthetized female rabbits in the following groups: 1) sham, 2) ovariectomy, 3) ovariectomy + 17β-estradiol, and 4) ovariectomy + dehydroepiandrosterone. After a 2-wk treatment, cardiac hemodynamics, vascular reserve, and blood flow were evaluated during the following infusions: 1) NaCl, or vehicle (0.5 ml/min), 2) acetylcholine (2 mg/kg), 3) isoproterenol (2 mg · kg−1 · min−1), and 4) chromonar (8 mg/kg). In hearts from ovariectomized rabbits, autoregulatory blood flow was preserved despite lower diastolic perfusion pressures (55 ± 8 vs. 64 ± 8 mmHg in sham) and rate-pressure product (14.4 ± 0.8 vs. 19.3 ± 0.8 beats/min · mmHg×10−3). Estrogen replacement therapy restored coronary pressure and reserve, and all drugs increased vascular conductance. In conclusion, in hearts from ovariectomized rabbits, vascular reserve declined because coronary pressure was lower; however, blood flow was preserved at a higher level than expected for oxygen demand. Estrogen replacement therapy restores myocardial oxygen supply-demand indices and returns coronary pressure-flow data to levels observed in animals with intact ovaries.

1996-02-19·FEBS Letters3区 · 生物学

Antioxidants differentially affect nuclear factor κB‐mediated nitric oxide synthase expression in vascular smooth muscle cells

3区 · 生物学

Article

作者: Markus Hecker ; Christiane Preiβ ; Rudi Busse ; Valérie B. Schini-Kerth

Increased ‘oxidative stress’ resulting in the activation of nuclear factor κB (NF‐κB) is thought to play a crucial role in the cytokine‐mediated expression of the inducible isoform of nitric oxide synthase (iNOS) in different cell types. Therefore, the effects of four different antioxidants, carbocromen, chrysin, 3,4‐dichloroisocoumarin (DCI) and N‐acetylserotonin (NAS), on iNOS expression were investigated in vascular smooth muscle cells (VSMC). All antioxidants strongly reduced the phorbol ester‐stimulated superoxide anion formation in native VSMC. Carbocromen (200 μM) and chrysin (50 μM) had no effect, while NAS (1 mM) abolished the increase in nitrine production and iNOS protein abundance in cultured VSMC exposed to interleukin‐1β (IL‐1β, 60 U/ml) or the adenylyl cyclase activator forskolin (10 μM). DCI also revealed a marked inhibitory effect in IL‐1β‐stimulated VSMC, but was less effective in cells treated with forskolin. DCI, but not NAS, also suppressed the activation of NF‐κB in VSMC exposed to IL‐1β, while no significant NF‐κB activation was detected in forskolin‐treated cells. These findings demonstrate that antioxidants differentially affect iNOS expression in VSMC both at the transcriptional level by preventing the activation of NF‐κB and at the post‐transcriptional level, presumably by promoting iNOS mRNA or protein degradation. They also suggest that reactive oxygen intermediates do not play a role in the activation of NF‐κB by IL‐1β in VSMC, and that transcripton factors other than NF‐κB mediate the induction of iNOS expression by elevating the intracellular concentration of cyclic AMP.

100 项与盐酸卡波罗孟相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	盐酸卡波罗孟	C01DX05	DB13279

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
心绞痛	中国	锦州九泰药业有限责任公司	1996-01-01
心律失常	中国	锦州九泰药业有限责任公司	1996-01-01
冠状动脉疾病	中国	锦州九泰药业有限责任公司	1996-01-01
心肌梗塞	中国	锦州九泰药业有限责任公司	1996-01-01