肾小球微血管构型的扫描电子显微镜观察

应用微血管铸型扫描电镜技术研究8例成人肾脏的肾小球微血管构筑,结果发现:1.输入小动脉在肾小球血管极处分为2～5支小球内小叶微动脉。输入小动脉血管铸型的直径为126.35±20.5μm。2.肾小球是由小球内小叶微动脉、毛细血管、毛细血管网小叶间交通支和毛细血管输出根所构成的近似于球状体,小球内每个毛细血管网小叶均是一个独立的机能解剖学单位;3.299个肾小球均有一支输出小动脉,只有一个肾小球有两支输出小动脉。输出小动脉的血管铸型直径为91.35±11.7μm。4.输出小动脉起始处具有毛细血管前括约肌装置,此结构在调控肾小球内的微循环血流有着重要意义。     

Sympathetic a-adrenergic control of large-bore arterial vessels,arterioles and veins,and of capillary pressure and fluid exchange in whole-organ cat skeletal muscle

The sympathetic nervous control of the vascular bed of cat gastrocnemius muscle was studied with a new whole-organ technique which permits simultaneous, continuous and quantitative measurements of capillary pressure (P_c), capillary fluid exchange and resistance reactions in the whole vascular bed and in its three consecutive sections: large-bore arterial vessels (> 25 μm), arterioles (< 25 μm) and veins. The results demonstrated a distinct neural control of all three consecutive vascular sections, graded in relation to the rate of nerve excitation up to maximum at 16 Hz. Stimulation at high rates, which in the steady state caused an average rise of overall regional resistance from 15.3 to 120 PRU (7.8-fold increase), thus raised large-bore arterial vessel resistance from 8.8 to 64 PRU (7.3-fold increase), arteriolar resistance from 4.5 to 49 PRU (10.9-fold increase) and venous resistance from 2.0 to 7 PRU (3.5-fold increase). The rate of resistance development (PRU s^-1) of the sympathetic constrictor response was much higher in the arteriolar than in the other sections, which indicates that the neural control is especially prompt and efficient in the arterioles. A passive component was shown to contribute to the described responses only on the venous side, but in no case by more than 10% of the total sympathetic venous resistance response, which thus is mainly active. Of special functional importance was that the new technique provided information about the adrenergic control of P_c, in absolute figures. From the control value of 19 mmHg, graded sympathetic stimulation caused a graded decline in P_c, at maximum constriction by about 7 mmHg. This resulted in marked net transcapillary fluid absorption, in turn increasing plasma volume.     

压力超负荷大鼠心、肺、肾血管重构的动态研究

目的 探讨压力超负荷与大鼠心、肺、肾内小动脉形态学重建的关系。方法 采用缩窄腹主动脉造成大鼠压力负荷模型，将大鼠随机分为两组：假手术组（SOG)和手术组(OG)。每组分为术后1、2、4、7、14、21、30、45、60d 9个时间点，对大鼠心、肺、肾组织连续切片，采用光镜配合计算机图像分析技术检测三个脏器小动脉几何形态的动态改变。结果 (1)随着压力负荷的增加，心、肺、肾小动脉的形态学重建可能存在时间顺序。(2)平均动脉压和造模时间与小冠状动脉和肾小动脉的壁腔比显著相关，而对小冠状动脉的管壁面积无影响；收缩压和造模时间与肾小动脉的管壁面积显著相关；造模时间与肺小动脉的壁腔比和管壁面积显著相关。结论 压力超负荷与心、肺、肾小血管的动态重构关系密切。小冠状动脉的重建以中膜平滑肌细胞的重排为主，肺、肾内小动脉的重建则可能存在中膜平滑肌细胞的肥大和增殖。     

Correlation between time lag of arterial–plethysmographic waveforms and systemic vascular resistance: a prospective study

Blood pressure (BP), a surrogate of cardiac output (CO), is also dependent on systemic vascular resistance (SVR). But SVR is not routinely monitored in daily clinical practice. We hypothesise that the time difference between the peripheral arterial waveform and the finger plethysmographic waveform (time lag index - TLi) could indicate the systemic vascular resistance. In this study, we correlated TLi with the systemic vascular resistance measured by minimally invasive CO monitor (pulse contour analysis). SVR changes in response to administration of mannitol were studied. American Society of Anesthesiologists (ASA) class I and II patients undergoing major intracranial surgeries were recruited. Arterial cannulation and pulse-oximetry recordings were done in the same limb. Arterial and plethysmographic waveforms were recorded before mannitol infusion (baseline) and at every 10 minutes for 60 minutes after the termination of mannitol infusion. Simultaneously, SVR was recorded from the Vigileo FLotrac CO monitor. Using custom-made programme, the time difference between both waveforms was calculated and corrected for heart rate (TLi). The correlation between time lag and the systemic vascular resistance was assessed using a mixed effect model, adjusting for the subject. Data of one hundred subjects were analysed. Following mannitol administration, there was a significant decrease in the SVR and the TLi (p?β?=?877.16, p?=?.008). The high beta coefficient suggests that when SVR increases, the TLi also increase and vice versa. A strong correlation between SVR and TLi was demonstrated for a given patient. Further studies are needed to explore the possibility of utilising this parameter to follow up changes in SVR in an individual patient at a particular point in time in different clinical scenarios.     

Mechanisms of enhanced basal tone of brain parenchymal arterioles during early postischemic reperfusion: role of ET-1-induced peroxynitrite generation

The contributions of vasoconstrictors (endothelin-1 (ET-1), peroxynitrite) and endothelium-dependent vasodilatory mechanisms to basal tone were investigated in parenchymal arterioles (PAs) after early postischemic reperfusion. Transient middle cerebral artery occlusion (tMCAO) was induced for 2 hours with 30 minutes reperfusion in male Wistar rats and compared with ischemia alone (permanent MCAO (pMCAO); 2.5 hours) or sham controls. Changes in lumen diameter of isolated and pressurized PAs were compared. Quantitative PCR was used to measure endothelin type B (ET_B) receptors. Constriction to intravascular pressure (‘basal tone'') was not affected by tMCAO or pMCAO. However, constriction to inhibitors of endothelial cell, small- (SK) and intermediate- (IK) conductance, Ca²⁺-sensitive K⁺ channels (apamin and TRAM-34, respectively) were significantly enhanced in PAs from tMCAO compared with pMCAO or sham. Addition of the ET_B agonist sarafotoxin caused constriction in PAs from tMCAO but not from sham animals (21±4% versus 3±3% at 1 nmol/L; P<0.01) that was inhibited by the peroxynitrite scavenger FeTMPyP (5,10,15,20-tetrakis (N-methyl-4′-pyridyl) porphinato iron (III) chloride) (100 μmol/L). Expression of ET_B receptors was not found on PA smooth muscle, suggesting that constriction to sarafotoxin after tMCAO was due to peroxynitrite and not ET_B receptor expression. The maintenance of basal tone in PAs after tMCAO may restrict flow to the ischemic region and contribute to infarct expansion.     

Signaling pathways of mechanotransduction in arteriolar endothelium and smooth muscle cells in hypertension

Hypertension, a disease with a high incidence in the population, affects all parts of the cardiovascular system. Studying the alteration of vasomotor responses of microvessels of hypertensive animals or responses of vessels following short-term increases in hemodynamic forces helps us to better understand the underlying cellular signaling events responsible for their functional adaptation. These adaptations are likely to precede the structural remodeling of arterioles, resulting in irreversible increases in peripheral vascular resistance in hypertension. Although malfunction of several mechanisms can lead to the development of hypertension, hemodynamic forces (such as pressure and shear stress) are increased in all forms of hypertension. Thus, local mechanisms that sense the level of these forces and transduce the signals into vasomotor responses must be affected in all forms of hypertension. The endothelium has a central role in the early functional adaptations. Pressure-induced myogenic constriction is enhanced due to the augmented release of endothelium-derived constrictor factors that modulate arteriolar smooth muscle sensitivity to Ca(2+). In contrast, flow/shear stress-induced dilation of arterioles is reduced in hypertension, due to the impaired mediation of the response by nitric oxide (NO). The magnitude of impairment is gender specific, primarily due to an estrogen-dependent enhancement of NO release in females. It is proposed that the elevated hemodynamic forces present in hypertension may themselves initiate these alterations, probably by enhancing the release of reactive oxygen species (ROS; produced by xanthine oxidase, NAD(P)H oxidoreductase, eNOS, etc.), which then interfere with the synthesis and/or action of endothelium-derived mediators. Interfering early on with these mechanisms may prevent the development of irreversible structural changes of the microcirculation observed in hypertension.     

Studies on the role of prostaglandins in the regulation of retinal blood flow

Prostaglandin E₁ was injected close to retinal arterioles by iontophoresis. Vasodilatation apparently similar to that caused by hypercapnia or hypoxia was observed. Inhibitors of prostaglandin synthetase were injected into the circulation. There was a reversible inhibition of the retinal vasodilation normally induced by hypercapnia. It is concluded that prostaglandin E₁ satisfies two criteria for a candidate for a mediator of hypercapnia-induced arteriolar dilatation. The effect of hypoxia appears more complicated.     

LOW DOSE INDAPAMIDE PLUS PERINDOPRIL COMBINATION EFFECTS ON CARDIOVASCULAR STRUCTURE AND FUNCTION IN GENETIC HYPERTENSION

1. Although the fixed combination preparations of thiazide and angiotensin-converting enzyme inhibitor are gaining wide acceptance in clinical practice, data on the basic pharmacology of the combinations are relatively limited. The long-term structural and functional effects of a fixed low dose (0.24 + 0.76 mg/kg per day) combination of indapamide + perindopril (I + P,S5590) is spontaneously hypertensive rats (SHR) were examined in the present study. 2. Male SHR (10-12 weeks) were treated with I + P or vehicle for 8 weeks. The blood pressure and heart rate were monitored by weekly measurements. At the end of the treatment period, left ventricular, aortic and intramyocardial coronary arteriole structures were assessed. Contractile and relaxant properties of mesenteric arteries were determined by wire-myography. 3. Indapamide + perindopril combination caused a significant lowering of both systolic (P < 0.001) and diastolic (P < 0.001) blood pressures. Left ventricle plus septum:bodyweight ratio (P < 0.001), aortic medial cross-sectional area (P < 0.05) and media:lumen ratios (P < 0.005) were all significantly reduced by I + P treatment. In contrast, the effect of I + P on intramyocardial coronary vascular structure did not reach statistical significance. There was some improvement in endothelium-independent vasorelaxation of mesenteric vessels but contractile responses to noradrenaline and calcium were unaffected by treatment. 4. In summary, a low dose I + P combination treatment of SHR partly normalizes both systolic and diastolic blood pressures. Cardiac and larger vessel hypertrophy was reversed but intramyocardial coronary arteriole structure was not as readily regressed by the end of the study.