Endothelial and smooth muscle properties of coronary and mesenteric resistance arteries in spontaneously hypertensive rats compared to WKY rats

Summary— To investigate if the functional alterations observed in resistance arteries of spontaneously hypertensive rats (SHRs) were also present at the coronary level, in vitro experiments were performed in mesenteric resistance arteries (MRA) and in right (RIC) and left interventricular coronary (LIC) arteries taken from 15–25-week-old SHR and age-matched Wistar Kyoto rats WKYs. Using a passive extension protocol, internal diameters corresponding to 100 mmHg intraluminal pressure (D₁₀₀) were determined and vessels were set up to a normalized internal diameter (0.9 D₁₀₀). SHR mesenteric resistance arteries had a significantly smaller diameter compared to WKY arteries, whereas both types of SHR coronary arteries had a greater diameter compared to those of WKY rats. In arteries in the absence of contracting agonist, nitro-L-arginine (NOLA, 100 μM) induced a progressive rise in basal tone, which could be reversed by subsequent addition of L-arginine (100 μM) but not D-arginine (100 μM). When expressed as percent of maximal contractions induced by agonists (noradrenaline, NA [10 μM] in MRA; serotonin, 5-HT [10 μM], in RIC and LIC), these contractions were significantly stronger in WKY compared to SHR coronary and mesenteric resistance arteries. In NA-precontracted MRA and 5HT-precontracted coronary arteries in the presence of indomethacin (10 μM), the magnitude of acetylcholine-induced maximal relaxations (expressed as percent of maximal contractions induced by agonists) was greater in WKY compared to SHR arteries. After a 30-min incubation period, NOLA (100 μM) completely inhibited relaxations induced by acetylcholine (0.01–10 μM) in all types of precontracted arteries. Subsequent additions of sodium nitroprusside, (SNP, 10 μM) induced complete relaxations in all preparations. These results show that a basal release of NO or NO-like compound by endothelial cells is present in isolated mesenteric resistance and coronary arteries of WKY rats and SHRs. The contribution of endothelium-derived relaxing factor-nitric oxide (EDRF-NO) to arterial tone was lower in MRA compared to coronary arteries in both strains and in SHR compared to WKY arteries. In the SHR preparations, the impaired relaxation induced by acetylcholine appeared to be due to a functional alteration of the endothelium in the presence of normal reactivity of the smooth muscle cells.     

THE INCREASE OF FEMORAL ARTERIAL FLOW BY STIMULATING THE DORSAL AND VENTRAL MEDULLA IN CATS

1. In chloralose-urethane anaesthetized cats, the dorsal cardiovascular reactive area (DCRA) in the parvocellular reticular nucleus dorsomedial to the facial nucleus, and the ventral cardiovascular reactive area (VCRA) ventromedial to the facial nucleus, were stimulated by microinjections of sodium glutamate (100–200 nmol) or electric current. 2. Stimulation of DCRA, with a long latency of 15–20 s, elicited a marked increase of blood flow in the contralateral femoral artery with little change to moderate increase in systemic arterial blood pressure (ABP). In the relatively dorsal portion of DCRA, however, a smaller increase of blood flow in the ipsilateral femoral artery was elicited. 3. On the other hand, stimulation of VCRA with a short latency (3–5 s) evoked an increase of blood flow in both femoral arteries which was more prominent on the contralateral side. The responses were accompanied with decreases in the blood flow of other vascular beds with only a slight increase or minimal change in ABP. 4. The data suggest that DCRA and VCRA are both viscerotopically organized to alter the resistance of individual vascular beds for redistribution of blood flow.     

肺血管扩张在肝肺综合征发病机制中作用的研究进展

肺血管扩张是肝肺综合征的主要发病机制,然而导致HPS肺血管扩张的机制相当复杂,至今仍不清楚.目前认为肺血管内巨噬细胞聚积和雌激素升高导致的血管活性因子增多和活性增强可能与此有关,近年来这方面的研究很多,本文对此作一综述.     

Hand and finger skin temperatures in convective and contact cold exposure

The present study aimed at investigating the spatial variability of skin temperature (T _sk) measured at various points on the hand during convective and cold contact exposure. A group of 8 subjects participated in a study of convective cooling of the hand (60 min) and 20 subjects to contact cooling of the finger pad (5 min). Experiments were carried out in a small climatic chamber into which the hand was inserted. For convective cold exposure,T _sk was measured at seven points on the palmar surface of the fingers of the left hand, one on the palmar surface and one on the dorsal surface of the hand. The air temperature inside the mini-chamber was 0, 4, 10 and 16°C. With the contact cold exposure, the subjects touched at constant pressures an aluminium cube cooled to temperatures of –7, 0 and 7°C in the same mini-chamber. ContactT _sk was measured on the finger pad of the index finger of the left hand. TheT _sk of the proximal phalanx of the index finger (on both palm and back sides), and of the middle phalanx of the little finger was also measured. The variation ofT _sk between the proximal and the distal phalanx of the index finger was between 1.5 to 10°C during the convective cold exposure to an air temperature of 0°C. Considerable gradients persisted between the hand and fingers (from 2 to 17°C at 0°C air temperature) and between the phalanges of the finger (from 0.5 to 11.4°C at 0°C air temperature). The onset of cold induced vasodilatation (CIVD) on different fingers varied from about 5 to 15 min and it did not always appear in every finger. For contact cold exposure, whenT _sk on the contact skin cooled down to nearly 0°C, the temperature at the area close to the contact skin could still be 30°C. Some cases of CIVD were observed in the contact skin area, but not on other measuring points of the same finger. These results indicated that local thermal stimuli were the main determinents of CIVD. Representative hand skin temperature may require five or more measuring points. Our results strongly emphasised a need to consider the large spatial and individual variations in the prediction and modelling of extremity cooling.     

The effects of nisoldipine alone and in combination with beta-adrenoceptor blockade on systemic haemodynamics and myocardial performance in conscious pigs

The peak effects of 10 mg nisoldipine p.o. with or without 80mg propranolol p.o. on systemic and regional haemodynamics inconscious pigs were investigated. Nisoldipine increased heartrate (70%), cardiac output (67%) and maxLVdP/dt (75%), but decreasedmean arterial pressure (21%) as systemic vascular conductanceincreased by 120%. Left ventricular systolic and end-diastolicpressures were not affected. Vasodilatation occurred in mostorgans. The increase in left ventricular blood flow (150%) favouredthe epicardial (195%) over the endocardial (110%) layers. Asa result the endo–epi blood flow ratio decreased by 30% When nisoldipine was administered simultaneously with propranolol,heart rate (29%), cardiac output (35%) and systemic vascularconductance (65%) increased, but maxL VdP/dt did not change.Mean arterial (18%) and left ventricular systolic (10%) pressuredecreased; left ventricular end-diastolic pressure was againunaffected. In most organs vasodilatation was attenuated, butstill present, compared to the changes after nisoldipine alone.The increase in epicardial blood flow (70%) again exceeded thatin endocardial blood flow (35%), however, the endo–epiratio decreased by only 15%. In the presence of propranolol,nisoldipine did not exert a negative inotropic action whilethe reflex-tachycardia was attenuated. In addition, no detrimentaleffects on perfusion of regional vascular beds were observed.     

冠心病患者肱动脉内皮和非内皮依赖性舒张机能的变化

采用高分辨力超声法测定 6 6例冠心病患者和 33例对照者在反应性充血时和含服硝酸甘油后的肱动脉内径变化。结果显示 :冠心病组血流介导的和硝酸甘油所致的肱动脉舒张反应均明显低于对照组 (均为 P <0 .0 5 ) ;血流介导的肱动脉舒张反应与高密度脂蛋白胆固醇呈正相关 ,与肱动脉基础内径、年龄和低密度脂蛋白胆固醇呈负相关 ;而硝酸甘油所致的肱动脉舒张反应则与血流介导的肱动脉舒张反应呈正相关 ,与肱动脉基础内径呈负相关。提示冠心病患者内皮依赖性和非内皮依赖性血管舒张机能均受损     

Direct cardiac and vascular actions of adrenomedullin in conscious sheep

1. Adrenomedullin (ADM) is a recently characterized circulating hormone which affects haemodynamic, renal and pituitary function in mammals. We have shown previously that in sheep, ADM produces vasodilatation together with increases in cardiac output and contractility. However, whether these effects are direct or mediated by autonomic reflexes is unclear. The present study examined the cardiovascular actions of an intravenous infusion of ADM in conscious, chronically instrumented sheep with either sympathetic, parasympathetic or autonomic ganglion blockade, to determine the role of the autonomic nervous system in mediating these cardiovascular changes.
2. Human ADM (1–52) was infused for 60 min at 2 μg kg⁻¹ h⁻¹ following: (1) saline control, (2) combined α/β-adrenoceptor (sympathetic) blockade (proporanolol 0.4 mg kg⁻¹ h⁻¹+phentolamine 0.15 mg kg⁻¹ h⁻¹ for 20 h), (3) muscarinic (parasympathetic) blockade (methscopolamine 0.05 mg kg⁻¹ h⁻¹ for 20 h) or (4) ganglion blockade (hexamethonium 3 mg kg⁻¹ h⁻¹ for 4 h). Measurements were made of mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), total peripheral conductance (TPC), maximal aortic flow (Fmax) and maximal rate of change of aortic flow (dF/dt).
3. ADM reduced MAP by 3±1 mmHg, and increased CO (1.2±0.2 l min⁻¹), HR (14±2 beats min⁻¹), TPC (21±3 ml min⁻¹ mmHg⁻¹), Fmax (2.3±0.8 l min⁻¹) and dF/dt (86±21 l min⁻¹ s⁻¹) in normal sheep. In animals with α/β blockade, similar changes were observed with ADM. However, during muscarinic blockade, the increases in HR (32±4 beats min⁻¹), CO (2.1±0.4 l min⁻¹), TPC (31±4 ml min⁻¹ mmHg⁻¹), Fmax (4.0±0.6 l min⁻¹), and dF/dt (150±12 l min⁻¹ s⁻¹) produced by ADM were enhanced. During ganglion blockade, ADM produced a greater reduction in MAP (−10±2 mmHg) compared to controls (−3±1 mmHg). However, there was no increase in HR. The changes in CO, TPC and contractility were similar to those observed in control animals.
4. These results suggest that the vasodilator effects of ADM on the periphery and its ability to increase CO and cardiac contractility are not mediated by the autonomic nervous system, but are probably the result of direct actions of ADM on the heart and vasculature.

     

益气化痰活血法对血脂正常的高血压患者血管内皮功能的影响

目的:探讨益气化痰活血法对血脂正常的原发性高血压(Essential Hypertension,EH)患者血管内皮功能的影响。方法:218例EH患者按1∶1随机分为对照组和试验组。前者给予常规西医治疗,后者在常规治疗基础上加用益气化痰活血法。治疗30d,比较两组的临床效果、内皮依赖性血管舒张功能(Flow-mediated Vasodilation,FMD)和收缩压。结果:疗程结束时,试验组总有效率显著高于对照组(97.25%VS 86.24%,P0.05);试验组FMD显著高于对照组[(8.17±0.85)%VS(6.26±0.74)%,P0.05];试验组SBP明显低于对照组[(128.64±17.35)VS(134.72±19.57),P0.05]。结论:在常规西医治疗基础上加用益气化痰活血法能显著提高血脂正常EH患者的临床疗效,改善FMD和降低SBP。