Increased sensitivity of cat cerebral arteries to serotonin upon elevation of transmural pressure

Segments of middle cerebral artery (MCA) were isolated from cat brains and cannulated allowing manipulation of transmural pressure (TP). These cannulated vessel segments were mounted in a specially fabricated myograph allowing measurement of internal diameter with the aid of a high resolution binocular microscope and a video imaging system. Internal diameter was then measured as a function of topically applied serotonin at 3 different levels of TP: 60, 100, and 140 mmHg. As TP was elevated from 60 to 140 mmHg the sensitivity to serotonin increased from an ED₅₀ value of 1.3×10^–8 to 3.5×10^–10 M. We have yet to explore the mechanisms involved in the pressure-mediated increase in cerebrovascular sensitivity to serotonin; however, it may be related to the muscle membrane depolarization we have observed previously in response to elevations in TP. Such findings may account for the discrepancies in dose ranges for serotonin thought to be activein vivo vs. the higher concentrations needed to elicit responses in isolated vessels.     

Influence of transmural pressure on myogenic responses of isolated cerebral arteries of the rat

We examined the diameter responses of isolated and pressurized posterior cerebral artery branches to various static and dynamic pressure alterations. These vessels, dissected from an anatomically identifiable location in the rat brain, developed tone when placed in a normal calcium physiological salt solution (1.6 mM Ca-PSS). Following a series of transmural pressure steps (Δp) of 25 or 50 mm Hg completed in 1–2 s and made every 5 min, they attained additional tone resulting in a mean luminal diameter of 139 μm at 100 mm Hg which was 35% less than their relaxed size measured in 1 mM EGTA-PSS. Continuous measurements of wall thickness and lumen diameter were obtained using a video electronic system in 1–2 mm long arterial segments, and autoregulatory gain factors calculated. Myogenic responses were obtained from each of 6 vessels taken from 6 WKY rats. Diameters following the step pressure changes were usually stable within 2–4 min. The data defined a myogenic regulatory pressure range from 49–145 mm Hg. Gain values averaged about 17% of that necessary for these arteries to maintain perfect flow autoregulation. Our results for myogenicity are comparable with the pressure range for blood flow autoregulation reported by others for the rat. We conclude that myogenic mechanisms, at least in this size artery, are partly responsible for flow autoregulation, and that they are supplemented by metabolic mechanisms operative in the intact rat brain. Research supported by grant HL 17335 from the NHLBI.     

Myogenic microvascular responses to change of transmural pressure A mathematical approach

The recently described static and dynamic myogenic responses in the sympathectomized skeletal muscle microvessels to a given transmural pressure (P_T) change applied at different rates (dP_Tldt) (Grände & Mellander 1978), were further analysed in this study with a mathematical approach. The hypothesis that myogenic reactions are triggered by and related to wall tension was also tested. The mathematical model was based on a force–equilibrium in the microvessel wall including passive forces related to vascular transmural pressure, elasticity, and wall–viscosity, and active myogenic forces related to wall tension and its rate of change. Great resemblance was demonstrated between microvascular resistance curves obtained with the model and corresponding curves observed in vivo, indicating that the model quite adequately can describe myogenic microvascular resistance responses to transmural pressure stimuli. The results support the myogenic hypothesis in general and, in particular, the concept of an important rate–sensitivity in myogenic microvascular control and are compatible with the view that myogenic reactions are triggered by and related to change of wall tension. The model, in addition, provided data for certain microvascular variables which are difficult to assess by in vivo observations, e.g. Young's modulus of elasticity, wall tension, its rate of change, and internal vessel radius, and it offered a means to define more precisely the role of physical factors like effects of Poiseuille's and Laplace's laws in vascular resistance regulation.     

The cerebral basal arterial network: morphometry of inflow and outflow components

The aim of this project was to study how the morphology of the incoming and outgoing arterial components of the cerebral basal arterial network influence the blood flow to the brain. The cerebral basal arterial network consists of the circulus arteriosus cerebri anteriorly and the basilar artery posteriorly. Diameters of inflow vessels (bilateral vertebral and internal carotid arteries), connecting vessels (anterior communicating, basilar and bilateral posterior communicating arteries) and outflow vessels (anterior, middle and posterior cerebral arteries) were measured and cross‐sectional areas calculated in 51 cadaveric brain specimens. The individual and the average cross‐sectional areas of inflow arteries (51.43 mm²) were significantly bigger than the major outflow arteries (37.76 mm²) but smaller than the combined cross‐sectional areas of outflow (37.76 mm²) and connecting (25.33 mm²) arteries. The difference in the size of arterial cross‐sectional area and the presence of the connecting arteries in the cerebral basal arterial network provides a mechanism for lowering peaks in pressure, and demonstrates a function of the cerebral basal arterial network.     

自发性高血压大鼠脑细小动脉神经肽Y分布的研究

为了解血管周围神经肽类分布与高血压时细小动脉构型重建之关系，我们采用自发性高血压大鼠（ＳＨＲ）软脑膜铺片技术，展示了血管网的各级分支，对血管系统进行了全面、立体的观察。并用免疫组织化学、图像分析仪对血管网上神经肽Ｙ（ＮＰＹ）分布进行定性定量分析。结果表明，ＳＨＲ大脑中动脉及其分支，小动脉、细动脉壁上含ＮＰＹ神经纤维分布表面积密度及ＮＰＹ抗体阳性反应物积分光密度均明显高于正常血压组（ＷＫＹ），这一实验结果揭示脑细小动脉含ＮＰＹ神经分布密度增加，使血管平滑肌营养调节作用增强，与其动脉收缩兴奋性增高，动脉平滑肌细胞肥大和高血压的发生发展有着明显关系。     

On the nature of basal vascular tone in cat skeletal muscle and its dependence on transmural pressure stimuli

The aim of the present study was to elucidate in some detail the characteristics of the intrinsic basal vascular tone in the adrenergically blocked skeletal muscle with regard to its extent and site along the vascular bed, its dependence on arterial pressure via static and dynamic transmural pressure stimuli, and its sensitivity to local metabolic influence. Basal tone, which apparently is of myogenic nature, was pronounced in ‘proximal arterial vessels’ (>25 μm i.d.) and in the ‘microvessels’ (<25 μm), but low in ‘large veins’. Its functional characteristics, however, were different in the ‘proximal arterial vessels’ and the ‘microvessels’. Normal basal tone in the ‘microvessels’ thus seemed to be intimately dependent on the arterial blood pressure level and, at least partly, initiated by its static mean pressure distension effect as well as by its dynamic pulse pressure oscillations. It could be virtually abolished by a transmural pressure decrease applied at fast rate (‘strong inhibitory dynamic transmural pressure stimulus’). Basal tone in the ‘proximal arterial vessels’, on the other hand, was little affected by arterial pressure and almost irresponsive to transmural pressure stimuli. Basal tone in the ‘microvessels’ was much more sensitive to metabolic stimuli than that in the ‘proximal arterial vessels’. The present results, viewed in the light of some recent electrophysiological studies on vascular smooth muscle, suggest that smooth muscle in the ‘microvessels’ is mainly of the spike-generating type, whereas that in the ‘proximal arterial vessels’ seems to be of different nature, possibly of the non-spike-generating type.     

脑动脉DSA形态分析及其意义

目的：探讨脑血管造影各主要动脉的投影规律及其分支的显示率，为脑血管疾病的影像诊断和介入治疗提供重要参考。方法：随机抽取140例全脑血管DSA系列图像，选择其中无脑血管疾病的51例进行观察。分别统计颈内动脉和椎动脉造影时正常脑血管各主要分支的显示率；归纳大脑前动脉A1段、大脑中动脉M1段及大脑后动脉P1段在平面上的投影规律并分析总结了脑动脉的正常解剖学特征及其变异。结果：①脑底动脉变异较大；②颈内动脉照影时OA、AChA、ACoA、PCoA、ACA和MCA的显示率分别为96.1％、92．2％、52．9％、69．6％、100％和100％；③椎动脉造影时PICA、AICA、BA、SCA、PCA和PCoA的显示率分别为66．7％、62．7％、100％、70．6％、80．4％和41．2％。结论：①尽管脑底血管实际解剖关系较为复杂，但造影时反映到平面上可简捷的用“水平、上升、下降”等来描述血管的形态和走行；②虽然是平面图像，通过调整投照体位仍可非常逼真的反映血流的动态变化。     

The infra-optic course of the anterior cerebral arteries: an anatomic case report

Although variations of the anterior part of the cerebral arterial circle of Willis are quite well known, though some anomalies are exceedingly rare. In a 61-year-old female individual, on both sides the precommunicating parts of the anterior cerebral artery were found to course inferiorly to the ipsilateral optic nerves. This anomaly was associated with an agenesis of a left posterior communicating artery. The anatomic features, the possible high prevalence of associated aneurysms of the anterior communicating artery complex as well as implications for surgical planning or endovascular treatment are outlined and embryologic considerations and discussed.     

Comparison of the effects of potassium and pH on the calibre of cerebral veins and arteries

The vasomotor responses of individual pial veins and arteries on the convexity of the cerebral cortex to perivascular microinjection of mock cerebrospinal fluid (CSF) containing various concentrations of potassium (K⁺) and of various pH (achieved by altering the bicarbonate, HCO ₃ ^– concentration) have been examined in cats anaesthetised with -chloralose.Microapplication of CSF containing 0 mM HCO ₃ ^– (pH 4.80) effected significant increases in calibre of pial veins and arteries of 9.3±2.4% and 38.2±4% respectively (mean calibre change ±SE), whereas CSF containing 22 mM HCO ₃ ^– (pH 7.45) which constricted pial arteries significantly (–18.5±2.9%) minimally altered venous calibre (–4.3 ±2.2%).Microapplication of CSF containing 0 mM potassium resulted in a significant reduction in pial arterial calibre (–11.4±2.8%) but failed to alter pial venous calibre (–0.3 ±0.6%). Perivascular microapplication of CSF containing moderately elevated potassium concentrations (10 mM) which effected marked, significant increases in pial arterial calibre (49.3±3.9%) did not significantly alter the calibre of the pial veins (mean response –1.6±2.4%). The perivascular administration of CSF containing a high concentration of potassium (40 mM) resulted in the significant constriction of both pial veins (–13.5±0.9%) and pial arteries (–47.2±6.3%). The magnitude of the response was significantly smaller in the pial veins.The relative insensitivity to K⁺ and pH of the pial veins as compared to pial arteries suggests that alteration in the chemical composition of the perivascular fluid are of lesser importance in the control of cerebrovascular capacitance than for the regulation of cerebrovascular resistance.     

Pharmacological characterization of postjunctional α-adrenoceptors in isolated feline cerebral and peripheral arteries

The vascular α-adrenoceptors in isolated feline cerebral, lingual and mesenteric arteries were characterized and compared. In the middle cerebral artery the relative order of potency for agonists was: clonidine>oxymetazoline>noradrenaline>phenylephrine which indicates that the postjunctional α-receptor in this vessel is of α₂-type. This view is further supported by the finding that yohimbine, but not prazosin, had a potent, mainly competitive blocking action. In peripheral arteries, clonidine was without effect. In these vessels, the potency difference between phenylephrine and oxymetazoline was more than 40 times less than in cerebral vessels. The pA₂-values for prazosin correlated well with pA₂-values found for the interaction of this drug with α₁-receptors in a variety of other tissues, thus suggesting the occurrence of an α₁-receptor in these arteries. However, the pA₂-values for yohimbine and rauwolscine correlated well with an α₂-receptor, suggesting also the presence of α₂-receptors. Schild plots for prazosin and rauwolscine in lingual arteries displayed slopes significantly lower than unity, which also supports the view of a mixture of α₁-and α₂-receptors in these vessels. However, the Schild plots for the antagonists in mesenteric arteries did not differ significantly from unity, a finding possibly indicating the presence of an α-receptor unable to differentiate between substances that in other tissues act preferentially on α₁- or α₂-receptors.     

卡介苗接种对高盐及肾动脉狭窄术诱导的高血压大鼠血压的影响

目的:观察卡介苗接种对高盐负荷及肾动脉狭窄所致高血压的影响,为寻找防治人类高血压的新方法提供实验依据。方法:以高盐食物喂饲及肾动脉狭窄术分别制作高盐性高血压(SH)及肾性高血压(RH)模型。高盐喂饲或肾动脉狭窄术后4周,选择高血压大鼠及正常对照大鼠进行实验。所有大鼠腹部皮下接种卡介苗一次,接种前及接种后每周测定血压变化情况,同时每时段收集24 h尿样并以Greiss反应法进行一氧化氮终产物NO₂^-及NO₃^-(UNOx)的测定。3周后大鼠分别取主动脉组织并用Western blot法检测iNOS蛋白水平。结果:卡介苗接种对正常大鼠血压无明显影响。但接种1周时,能使高血压大鼠的血压明显下降。其中尤以卡介苗接种+L-精氨酸作用明显。NO测定表明,卡介苗接种后体内NO生成明显增加。Western blot结果证明卡介苗接种后,高血压大鼠主动脉血管组织中iNOS蛋白明显高于正常大鼠。结论:卡介苗接种能通过激活iNOS/NO途径降低某些类型高血压大鼠的血压。     

A morphometric study of the effect of bilateral cervical sympathetic ganglionectomy on the architecture of pial arteries in spontaneously hypertensive and normotensive rats

The influence of the cranial sympathetic nerves on the architecture of pial arteries in normo- and hypertension was examined. For this purpose the effect of bilateral superior cervical ganglionectomy was evaluated in normotensive rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). The operations were performed at the age of 1 wk, which is just prior to the onset of ganglionic transmission. The length of the inner media contour was measured and the media cross-sectional area was determined planimetrically, with computerized digitalization of projected photographic images of transversely sectioned pial arteries. Four wk after sympathectomy there was a 20% reduction in media cross-sectional area and a consequent reduction in the ratio between media area and calculated luminal radius in the major pial arteries at the base of the brain in WKY but not in SHRSP. Conversely, in small pial arteries linear regression analysis showed that in WKY subjected to ganglionectomy the relationship between media cross-sectional area and luminal radius was significantly larger in arteries with a radius less than 21 μm compared to untreated WKY. No such effect was seen in the corresponding SHRSP vessels. In addition, the cross-sectional area of the internal elastic membrane (IEM) in the basilar arteries of WKY was measured by means of a computerized image-analysing system. Mean cross-sectional area of the IEM was approximately 45% larger following SE than in control animals. The present findings propose a ‘trophic’ role for the sympathetic perivascular nerves in large pial arteries of the rat. The increased media-radius ratio in the small pial arteries of the WKY following sympathectomy might reflect a compensatory hypertrophy due to reduced protection from the larger arteries against the pressure load. The inability to detect any morphometrically measurable effect of the sympathectomy in the cerebral arteries of SHRSP is probably explained by a marked growth-stimulating effect of the high pressure load in these animals.     

The effects of pinacidil and tolbutamide in feline pial arteries in situ

The vasomotor effect of the K⁺ channel opener pinacidil was investigated in feline pial arteries of the parietal cortex. Perivascular microapplication (5l in 40 sec) and an image splitting method for the measurement of vascular diameter were employed. Pinacidil (10^–11 –10^–7 M) induced concentration-dependent dilatations at 10^–9 M and higher concentrations. A maximal dilatation of about 42% was achieved at 10^–8 M, the dilatation at 10^–7 M was reduced to 22%. The sulphonylurea tolbutamide exerted per se no effect in pial arteries but it blocked concentration-dependently the pinacidil induced dilatation. This is consistent with the presence of ATP-sensitive K⁺ channels in pial arteries which are closed under resting conditions.