Effect of Citrus paradisi extract and juice on arterial pressure both in vitro and in vivo

Citrus paradisi (grapefruit) consumption is considered as beneficial and it is popularly used for the treatment of a vast array of diseases, including hypertension. In the present study, the coronary vasodilator and hypotensive effects of Citrus paradisi peel extract were assessed in the Langendorff isolated and perfused heart model and in the heart and lung dog preparation. In both models, Citrus paradisi peel extract decreased coronary vascular resistance and mean arterial pressure when compared with control values (60 ± 15 × 10⁷ dyn s cm^?5 vs 100 ± 10 × 10⁷ dyn s cm^?5 and 90 mmHg vs 130 ± 15 mmHg, respectively). These decreases in coronary vascular resistance and mean arterial pressure were blocked when isolated and perfused hearts and mongrel dogs were pre‐treated with L‐NAME. In humans, Citrus paradisi juice decreased diastolic arterial pressure and systolic arterial pressure both in normotensive and hypertensive subjects. Citrus paradisi juice produced a greater decrease in mean arterial pressure when compared with Citrus sinensis juice, cow milk and a vitamin C‐supplemented beverage. However, more detailed studies are required to isolate, purify and evaluate the chemical compounds responsible for this pharmacological effect and to clarify its possible role for treating hypertension. Copyright © 2009 John Wiley & Sons, Ltd.     

电刺激糖尿病大鼠血管舒张神经反应性变化的研究

目的 :研究不同病期的糖尿病大鼠外周血管舒张神经是否发生病变。方法 :将不同病期链佐霉素(STZ)性糖尿病及对照组大鼠制成毁脑脊髓大鼠模型 ,在用六烃季胺阻断内源性去甲肾上腺素释放及在甲氧明升压基础上 ,对比观察了脊髓内电刺激诱发的外周血管舒张效应。结果 :4周和 8周糖尿病大鼠脊髓内电刺激诱发的血管舒张反应未见明显改变 ,而 12周糖尿病大鼠反应性明显降低。结论 :随着糖尿病病程的延长及病情的进展 ,外周血管舒张神经可能发生病变而导致其功能降低。     

Haemodynamic effects of different doses of dopexamine hydrochloride in low cardiac output states following cardiac surgery.

We studied the haemodynamic effects of dopexamine hydrochloride, a beta 2-adrenergic agonist with dopaminergic (DA1) activity, in 20 patients with low cardiac output following surgery for coronary artery bypass grafting and/or valve replacement or repair. Following titration of four doses (1, 2, 4 and 6 micrograms.kg-1.min-1), the dose producing the optimal response was infused for up to 48 h (five patients). During the infusion, significant increases in cardiac index and stroke volume were accompanied by significant decreases in systemic vascular resistance. Heart rate increased significantly up to 6 h and thereafter returned to control levels. Mean blood pressure was reduced but did not fall below 60 mmHg. However, in five patients treated for 48 h mean blood pressure had returned to control levels. Unwanted effects (tachycardia and hypotension) were seen chiefly at higher doses, leading us to conclude that infusion rates of 4 micrograms.kg-1.min-1 or less will be useful in the treatment of low cardiac output following cardiac surgery.     

Haemorheologic studies in patients with reduced coronary vasodilator capacity but normal coronary angiogram (syndrome X)

The cause of syndrome X, i.e. typical angina, positive exercisetest, normal coronary angiogram, normal resting cardiac function,but reduced coronary vasodilator capacity is still unknown.The purpose of the study was to investigate blood fluidity asa possible cause of syndrome X. Haematocrit, plasma viscosity,erythrocyte aggregation, and erythrocyte deformability wereexamined in 14 patients with syndrome X (group 1), 24 patientswith typical angina, positive exercise test, but normal coronaryvasodilator capacity (group 2), and 37 patients with atypicalchest pain and normal coronary arteries (control group). Coronaryvasodilator capacity was determined by the argon method. Comparedwith normals, patients with syndrome X showed an elevated plasmaviscosity (1.31 ±0.05 mPas vs l.26±0.04 mPas,2P>001), an elevated erythrocyte photometric aggregationindex (141 ±27% vs 100 ±23%, 2?>001) and areduced erythrocyte filterability (0.51 ±0.12 vs 0.66± 0.09, 2P > 0.01). Significant differences in thehaemorheologic parameters between group 1, group 2 and the controlgroup, however, were not detected. Multiple regression analysisdid not reveal a significant relationship between coronary vasodilatorcapacity and the haemorheologic parameters tested. The datasuggest that the reduction in coronary vasodilator capacityin patients with syndrome X cannot be attributed to haemorheologicalterations.     

Long-term effects of pinacidil in hypertensive dialysis patients

Summary In an open study, thirteen chronic dialysis patients with nonvolume dependent uncontrolled hypertension were treated with pinacidil for a mean period of 43 weeks. Seven patients were taking concomitant antihypertensive therapy. Twelve patients achieved long-term blood pressure control on a mean dose of 33 mg/day. The baseline supine blood pressure was 184/116 mmHg. After 1 week it had fallen to 161/95 mmHg and blood pressure control was maintained over the study period.Patient weight remained stable. The baseline reading was 61.6 kg and at the end of the study it was 59.7 kg. Pulse rate did not change significantly. For the eight patients not taking beta-blockers the mean change in pulse rate was 7.6 beats/min supine and 6.3 beats/min erect (NS). Pretrial urea and creatinine were 27.6 mmol/l and 1027 µmol/l and after 25 weeks they were 29.6 mmol/l and 1087 µmol/l, respectively (NS). Four patients had ECG evidence of left ventricular hypertrophy before the study and one on completion of the trial. Five patients showed correction of T-waves on their ECG's. Six patients experienced side effects, none of which warranted withdrawal of treatment. These findings suggest that pinacidil is a valuable alternative treatment for hypertensive dialysis patients.     

Impaired endothelium-dependent vasodilation of coronary resistance vessels in severely stunned porcine myocardium

The effect of stunning on endothelium-dependent responses of resistance vessels in vivo remains of interest. We utilized the coronary pressure-flow relationship during maximal vasodilation in anesthetized swine to identify subtle changes in flow reserve within stunned myocardium. Prior to and following stunning, the coronary pressure-flow relationship during maximal doses of intracoronary adenosine was compared with that of the endothelium-dependent vasodilator ATP. In 11 anesthetized swine, 30 min of partial LAD occlusion and 40 min of reperfusion reduced fractional shortening from 16±4% to 6±5% (p<0.05). This caused a rigtward shift of the coronary pressure-flow relationships during infusions of either adenosine or ATP, suggestive of increased extra vascular compressive forces. With adenosine, the slope of the linear portion of the relationship (i.e., coronary pressures >30 mmHg) was 1.31±0.54 ml/min-mmHg at baseline and 1.30±0.55 ml/min-mmHg following stunning (NS). With ATP however, the slope decreased from 1.34±0.48 ml/min-mmHg at baseline to 1.08±0.47 ml/min-mmHg following reperfusion (p<0.05), indicating an attenuation of endothelium-dependent vasodilator capacity. In five of the animals, the slope of the pressure-flow relationship during intracoronary nitroprusside was unchanged post-stunning, side was unchanged post-stunning, which is similar to the adenosine results. In conclusion, the data support the hypothesis that endo-thelium-dependent vasodilation of resistance vessels in the intact animal is altered within severely stunned myocardium. The rightward shift of the coronary pressure-flow relation ships with both classes of vasodilators suggest that extra vascular factors may also play a role in limiting coronary flow reserve.Supported by grants from the Minnesota Medical Foundation, American Heart Association-Minnesota Affiliate and VA Merit Review (E.O.M.)     

Studies on vasodilatation in the hand on exposure to heat

Summary In five subjects whose hands were exposed to heat, no depletion in the plasma kininogen level was observed when vasodilatation occurred. This might be due to the admixture of arterial and venous blood following the opening of arterio-venous (A-V) anastomoses. The small rise obtained by warming was not significant (P>0.1). Consequently, the drop in kinonogen concentration recorded when the hand was allowed to cool to an ambient temperature of 23 C as compared with the basal level and that during the period of warming, was also found to be non-significant.In another nine subjects whose A-V kininogen values were determined when their hands were immersed in a water bath at 37 C, a significant A-V difference of the kininogen content was obtained.From this work, it is concluded that no appreciable depletion of venous kininogen concentration was obtained on hand warming. It is possible that sweat glands, vasodilator nerve fibres and the release of kinins contribute in part to the dilatation that occurs.Possible patho-physiological mechanisms involved are discussed.     

EFFECT OF RESERPINE ON RELAXANT RESPONSES OF CANINE FEMORAL ARTERIAL STRIPS

1 We studied relaxant responses to adenosine, glyceryl trinitrate, and hydralazine in control (n = 5) and reserpine pretreated (1 mg/kg i.m., 24 h prior; n = 5) canine femoral arterial strips contracted with noradrenaline. 2 Reserpine did not alter contractile responses to noradrenaline. 3 Reserpine pretreated tissues were supersensitive to glyceryl trinitrate, but not to adenosine or hydralazine.     

急性心力衰竭治疗的新药重组人松弛素

目的:最近重组人松弛素的临床试验为急性心力衰竭(AHF)的治疗提供了新的希望,笔者主要对重组人松弛素的作用机制、药理学特性、临床特征及治疗AHF的作用做一综述。方法:使用Pubmed/Medline database对文献进行查找,收集到21篇相关文献。结果 :研究表明重组人松弛素显著改善AHF患者的症状,缩短住院时间,降低病死率。目前的资料表明这些临床益处与重组人松弛素的多效性有关,包括改善全身、心脏和肾脏血流动力学,通过抗炎、抗细胞死亡、抗纤维化、抗心肌肥厚及促进血管新生保护细胞和器官免受损伤。结论 :重组人松弛素是一种有前景的治疗AHF药物。正在进行中的研究旨在验证先前的试验结果、安全性和血流动力学效应,探讨这些效应的分子机制。