扎普司特和谷胱甘肽翻转豚鼠离体气管对硝普钠的耐受性

上皮完整或去上皮的豚鼠离体气管以300 μmol·L^-1硝普钠(SNP)预处理1 h,使SNP对抗乙醋甲胆碱气管收缩作用的剂量反应曲线右移1.3-1.5 倍, 最大舒张率下降41%-58%,形成SNP气管松弛作用的耐受性. 8-溴环鸟苷酸可模拟SNP在豚鼠离体气管形成的SNP耐受性, 谷胱甘肽(1 mmol·L^-1)及环核苷酸磷酸二酯酶(PDE) Ⅴ抑制剂扎普司特(30 μmol·L^-1)均可部分翻转SNP 的气管松弛作用耐受性,而蛋白合成抑制剂环己酰亚胺(10 μmol·L^-1)对SNP的耐受性无预防作用.结果表明SNP可产生豚鼠离体气管松弛耐受性, 这可能是由于气管平滑肌中环鸟苷酸(cGMP)积聚而下调鸟苷酸环化酶(GC)活性和上调PDEⅤ活性.     

吡那地尔与硝苯啶对大鼠离体工作心脏的影响

在大鼠离体工作心脏上，ＡＴＰ敏感性Ｋ＋通道开放剂吡那地尔（ＰＩＮ）１～１０μｍｏｌ／Ｌ可加快心率，１０μｍｏｌ／Ｌ产生负性肌力作用，使主动脉射量略有下降，但不影响冠脉流量。０．１μｍｏｌ／Ｌ二氢吡啶类钙拮抗剂硝苯啶（ＮＩＦ）可减慢心率，降低主动脉射量，１．０μｍｏｌ／ＬＮＩＦ有明显的负性肌力及负性频率作用，主动脉射量显著下降，冠脉流量变化不明显。提示ＰＩＮ及ＮＩＦ均可直接作用于心脏，但二者的作用性质及作用强度不同，ＰＩＮ有较轻的正性频率和负性肌力作用，ＮＩＦ有明显的负性频率和负性肌力作用     

Involvement of endothelium-derived NO in the basal tone and in the vasodilator responses to muscarinic agonists in the rat isolated mesenteric arterial bed

Summary— To investigate the involvement of nitric oxyde (NO) derived from endothelial cells in the control of vascular tone in the rat mesenteric vascular bed, the effects of different procedures known to interfere with the NO-cyclic GMP pathway were evaluated both on the basal tone and on the vasodilatory responses to four muscarinic agonists. To this aim, rat isolated mesenteric vascular beds were perfused at constant pressure. Water infusion significantly increased the resting perfusion pressure whereas L-NOARG, L-NAME and methylene blue were devoid of effect. In noradrenaline-preconstricted vascular bed, the perfusion pressure was significantly increased after water or L-NAME infusion. The vasodilator response induced by subsequent addition of acetylcholine in bolus was not significantly modified by pre-treatment with indomethacin but was significantly reduced by water infusion. Reponses to acetylcholine and to three other muscarinic agonists -carbachol, oxotremorine or McNeil A 343- were assessed. Incubation with L-NAME did not modify the initial peak falls of the agonists except for Mc Neil A 343, whereas it significantly reduced the area under the pressure trace for all the substances. The latter effect was reversed after a subsequent incubation with L-Arginine. Finally, L-NAME strongly and significantly increased the drop in perfusion pressure and the area under the pressure trace following bolus of glyceryl trinitrate. These results suggest that in the mesenteric arterial bed of the rat, which can be considered as a resistant arteries preparation, basal tone appears to be controlled by a factor other than NO. Moreover, the vasodilator responses of muscarinic agonists are affected by L-NAME in their second late sustained phase only, which probably relies on a de novo synthesis of endothelium derived-NO. Finally, endothelium derived-NO exerts inhibitory effects both on the sensitivy of the vascular smooth muscle to glyceryl trinitrate and on the magnitude of its contraction in the presence of noradrenaline, two types of effects which are sensitive to L-NAME.     

Features of the hemodynamic response to amyl nitrite inhalation: Ew aspects of an old tool

Although amyl nitrite inhalation (ANI) antedates current short acting vasodilators as a clinically useful pharcologic stressor, few clinicians are aware of the subtle hemonamic actions of this agent. This study examined transients left and right heart hemodynamics after ANI in seven men ages 44 ± 7 years) undergoing elective cardiac catheterization. -fidelity central aortic (AoP), left ventricular (LVP), pulonary artery (PAP), right ventricular (RVP), and right atrial (PAP) pressures were simultaneously recorded from left and right heart multisensor catheters. As expected, ANI caused an fall in Ao pressure (27%; p<0.01) and reflex (p<0.001). Little change was noted in PAP, RVP, RAP, or end-diastolic pressures or the time constant of LV isovolnetric relaxation (tau). LV ejection time decreased 23 ± 10 (p<0.05) and RV ejection time did not change. Baroreflex was similar during pressure fall and recovery (6.4 ± vs. 6.1 ± 3.6 ms/mmHg), however hysteresis (p<0.05) was. Aortic pressure waveforms also changed following ANI. Changes were determined to be in part a consequence of the atanuation and delay in arterial wave reflections. This study the understanding of the complex nature of the hemodynamic response associated with ANI.     

Chronic oral vasodilator therapy to control heart failure in postinfarction ventricular septal defect

This report describes a 70-year-old woman with biventricular failure following an anteroseptal infarction complicated by interventricular septal rupture. Treatment with nitroprusside followed by oral hydralazine eliminated the failure and reduced the shunt from 2.75 to 1 to 1.7 to 1. She is asymptomatic post-discharge. Chronic medical therapy including oral vasodilators may be an acceptable alternative to surgery in a small minority of patients with this complication of myocardial infarction.     

Lidoflazine: Double-blind trial of a new coronary vasodilator in angina pectoris

Summary Lidoflazine, a new coronary vasodilator, has been tested in 31 cases of angina pectoris in a double-blind cross-over study. It diminished significantly the frequency of attacks and nitroglycerine consumption of the more severe cases, but its effects were less marked in milder cases. The results are discussed in relation to other anti-anginal drugs. The necessity for a preliminary run-in period in studies of angina pectoris is emphasized and the occurrence of carry-over effects between lidoflazine and the placebo is discussed.     

Effects of a stable prostaglandin analogue,L-644,122, in healthy and hypertensive men

Summary L-644,122 is a chemically stable vasodilator prostaglandin analogue. It is a selective renal vasodilator in dogs. The object of the present study was to determine whether it increases effective renal plasma flow (ERPF) in man. L-644,122 was administered intravenously to 4 healthy volunteers and by mouth to 4 mild hypertensives. It did not increase ERPF. Instead it acted as a non-specific vasodilator, lowering diastolic blood pressure and increasing heart rate. An unexpected increase in glomerular filtration rate (19% greater than placebo) after low dose intravenous L-644,122 merits further study.     

Vasodilator therapy with hydralazine induces angiotensin AT2 receptor-mediated cardiomyocyte growth in mice lacking guanylyl cyclase-A

Background and purpose:

Recent clinical guidelines advocate the use of the isosorbide dinitrate/hydralazine combination in treatment for heart failure. However, clinical and laboratory evidence suggest that some vasodilators may induce cardiac hypertrophy under uncertain conditions. This study investigated the effects and underlying mechanism of action of the vasodilator hydralazine on cardiac growth.

Experimental approach:

Wild-type mice and animals deficient in guanylyl cyclase-A (GCA) and/or angiotensin receptors (AT₁ and AT₂ subtypes) were treated with hydralazine (≈24 mg·kg⁻¹·day⁻¹ in drinking water) for 5 weeks. Cardiac mass and/or cardiomyocyte cross-sectional area, fibrosis (van Giessen-staining) and cardiac gene expression (real-time RT-PCR) were measured.

Key results:

Hydralazine lowered blood pressure in mice of all genotypes. However, this treatment increased the heart and left ventricular to body weight ratios, as well as cardiomyocyte cross-sectional area, and cardiac expression of atrial natriuretic peptide mRNA in mice lacking GCA. Hydralazine did not affect cardiac hypertrophy in wild-type mice and mice lacking either AT₁ or AT₂ receptors alone. However, the pro-hypertrophic effect of hydralazine was prevented in mice lacking both GCA and AT₂, but not GCA and AT₁ receptors. However, hydralazine did decrease cardiac collagen deposition and collagen I mRNA (signs of cardiac fibrosis) in mice that were deficient in GCA, or both GCA and AT₂ receptors.

Conclusions and implications:

The vasodilator hydralazine induced AT₂ receptor-mediated cardiomyocyte growth under conditions of GCA deficiency. However, attenuation of cardiac fibrosis by hydralazine could be beneficial in the management of cardiac diseases.     

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Abstract

A life-threatening intoxication, requiring ventilatory support, is reported from the ingestion of 3.05?g of buflomedil, a peripheral vasodilator. Buflomedil at a dosage of 50?mg/kg weight produces seizures. Hypotension is not a specific symptom of intoxication. Buflomedil poisoning can be easily confused with other drugs, especially tricyclic antidepressants.