氟伐他汀对自发性高血压大鼠阻力血管结构和功能的影响

目的 探讨氟伐他汀对自发性高血压大鼠（ＳＨＲ）阻力血管结构和功能的影响。方法 ＳＨＲ大鼠出生后８周给予氟伐他汀２０ｍｇ．ｋｇ＾－１．ｄ＾－１。应用计算机图象分析,计算血管壁腔比,观察三组大鼠肠系膜动一级分支及主动脉结构变化,采用离体的主动脉和肠系膜动脉环在管活性药物：去甲肾上腺素和硝普钠反应的敏感性,观察治疗后血管的功能变化。结果 治疗８周后,氟伐他汀组（ＳＨＲｆｌｕ）收缩压比对照组（ＳＨＲ）平均     

Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions

Oxygen transport imposes a possible constraint on the brain''s ability to sustain variable metabolic demands, but oxygen diffusion in the cerebral cortex has not yet been observed directly. We show that concurrent two-photon fluorescence imaging of endogenous nicotinamide adenine dinucleotide (NADH) and the cortical microcirculation exposes well-defined boundaries of tissue oxygen diffusion in the mouse cortex. The NADH fluorescence increases rapidly over a narrow, very low pO₂ range with a p₅₀ of 3.4±0.6 mm Hg, thereby establishing a nearly binary reporter of significant, metabolically limiting hypoxia. The transient cortical tissue boundaries of NADH fluorescence exhibit remarkably delineated geometrical patterns, which define the limits of tissue oxygen diffusion from the cortical microcirculation and bear a striking resemblance to the ideal Krogh tissue cylinder. The visualization of microvessels and their regional contribution to oxygen delivery establishes penetrating arterioles as major oxygen sources in addition to the capillary network and confirms the existence of cortical oxygen fields with steep microregional oxygen gradients. Thus, two-photon NADH imaging can be applied to expose vascular supply regions and to localize functionally relevant microregional cortical hypoxia with micrometer spatial resolution.     

A quantitative ultrastructural study of juxtaglomerular arterioles in IDDM patients with micro- and normoalbuminuria

Summary Hyalinization of juxtaglomerular arterioles is prominent in advanced diabetic nephropathy and may have important functional consequences. We studied the early stages of diabetic renal disease using kidney biopsy material from insulin-dependent diabetic patients, 8 with normal albumin excretion rate (<15 /min) and 16 with microalbuminuria (15–200 g/min). Ten living non-diabetic kidney donors served as a control group. Median duration of diabetes was 9.5 years (range 5–31) in patients with normoalbuminuria, and 12 years (7–22) in patients with microalbuminuria (p=0.27). The tissue was sectioned systematically, 1-m thick sections for light microscopy at 10-m intervals, and thin sections for electron microscopy taken at 60-m intervals. The arterioles were identified as afferent or efferent, and total profiles were photographed (magnification 7500×), providing a systematic independent sample for measurements using standard stereological methods. Patients with microalbuminuria had significantly increased arteriole parameters compared with the control group: for afferent and efferent arterioles the volume fraction of matrix/media, means and (coefficient of variation, CV), was 0.47 (0.16) vs 0.33 (0.19) (p=0.0009), and 0.62 (0.14) vs 0.45 (0.23) (p=0.0004) and matrix-T, expressing amount of matrix per unit arteriolar surface, 2.38 (0.38) m vs 1.44 (0.30) m (p=0.004), and 1.62 (0.28) m vs 1.03 (0.34) (p=0.0009). Patients with normoalbuminuria showed no significant differences from the control group, and had lower values than microalbuminuric patients for all parameters except the afferent matrix-T. In the normoalbuminuric group a correlation was found between parameters for afferent arterioles and those for glomerular structure. In conclusion there is arteriolar accumulation of extracellular material in the early phase of diabetic nephropathy, concomitant with early glomerulopathy.Abbreviations IDDM Insulin-dependent diabetes mellitus - GFR glomerular filtration rate - AER albumin excretion rate - matrix-T matrix thickness - ND non-diabetic subjects - D_NA IDDM patients with normal albumin excretion rate - D_MI IDDM patients with microalbuminuria - RPF renal plasma flow - CV coefficient of variation     

The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood‐Brain Barrier Permeability

Objective : We investigated the effect of estrogen replacement on the structure and function of penetrating brain arterioles (PA) and blood‐brain barrier (BBB) permeability. Materials and Methods : Female ovariectomized Sprague‐Dawley rats were replaced with estradiol (E₂) and estriol (E₃) (OVX + E;N=13) and compared to ovariectomized animals without replacement (OVX; N=14) and intact controls (CTL, proestrous; N=13). Passive and active diameters, percent tone, and passive distensibility of pressurized PA were compared. In addition, BBB permeability to Lucifer Yellow, a marker of transcellular transport, was compared in cerebral arteries. Results : Ovariectomy increased myogenic tone in PA, compared to CTL, that was not ameliorated by estrogen treatment. Percent tone at 75 mmHg for CTL vs. OVX and OVX + E was 44±3% vs. 51±1% and 54±3% (P<0.01 vs. CTL for both). No differences were found in passive diameters or distensibility between the groups. BBB permeability increased 500% in OVX vs. CTL animals; however, estrogen replacement restored barrier properties: flux of Lucifer Yellow for CTL, OVX, and OVX + E was (ng/mL): 3.4±1.2, 20.2±5.3 (P<0.01 vs. CTL), and 6.15±1.2 (n.s.). Conclusions : These results suggest that estrogen replacement may not be beneficial for small‐vessel disease in the brain, but may limit BBB disruption and edema under conditions that cause it.     

Hypoxia inhibits contraction but not calcium channel currents or changes in intracellular calcium in arteriolar muscle cells

OBJECTIVE: We tested the hypothesis that hypoxia inhibits currents through L-type Ca(2+) channels and inhibits norepinephrine-induced rises in intracellular Ca(2+) in cremasteric arteriolar muscle cells, thus accounting for the inhibitory effect of hypoxia on norepinephrine-induced contraction of these cells. METHODS: Single smooth muscle cells were enzymatically isolated from second-order and third-order arterioles from hamster cremaster muscles. The effects of hypoxia (partial pressure of oxygen: 10-15 mm Hg) were examined on Ba(2+) (10 mM) currents through L-type Ca(2+) channels by use of the perforated patch clamp technique. Also, the effect of hypoxia on norepinephrine-induced calcium changes was studied using Fura 2 microfluorimetry. RESULTS: Hypoxia inhibited the norepinephrine-induced (10 microM) contraction of single arteriolar muscle cells by 32.9 +/- 5.6% (mean +/- SE, n = 4). However, hypoxia had no significant effect on whole-cell currents through L-type Ca(2+) channels: the peak current densities measured at +20 mV were -3.83 +/- 0.40 pA/pF before hypoxia and -3.97 +/- 0.36 pA/pF during hypoxia (n = 15; p > 0.05). In addition, hypoxia did not inhibit Ca(2+) transients in arteriolar muscle cells elicited by 10 microM norepinephrine. Instead, hypoxia increased basal Ca(2+) (13.8 +/- 3.2%) and augmented peak Ca(2+) levels (29.4 +/- 7.3%) and steady-state Ca(2+) levels (15.2 +/- 5.4%) elicited by 10 microM norepinephrine (n = 21; p < 0.05). CONCLUSIONS: These data indicate that hypoxia inhibits norepinephrine-induced contraction of single cremasteric arteriolar muscle cells by a mechanism that involves neither L-type Ca(2+) channels nor norepinephrine-induced Ca(2+) mobilization. Instead, our findings suggest that hypoxia must inhibit norepinephrine-induced contraction by affecting a component of the signaling pathway that lies downstream from the increases in Ca(2+) produced by this neurotransmitter.     

高血压病患者脉压差与颈动脉粥样硬化的相关性研究

目的探讨高血压病患者脉压差与颈动脉粥样硬化斑块的发生率及颈动脉内中膜厚度(IMT)的相关性。方法通过多普勒超声检查70例高血压患者颈动脉粥样硬化斑块及IMT,计算出这些患者的脉压差,观察脉压差与颈动脉粥样硬化斑块的发生率及与颈动脉内中膜厚度(IMT)的相关性。结果脉压差大的患者其颈动脉粥样硬化斑块的发生率及IMT均增高(P<0．05)。结论脉压差与颈动脉粥样硬化斑块和IMT相关,脉压差可促进动脉粥样硬化的形成和发展。     

The Effects of Diuretics on Intracellular Ca2+ Dynamics of Arteriole Smooth Muscles as Revealed by Laser Confocal Microscopy

The regulation of cytosolic Ca²⁺ homeostasis is essential for cells, including vascular smooth muscle cells. Arterial tone, which underlies the maintenance of peripheral resistance in the circulation, is a major contributor to the control of blood pressure. Diuretics may regulate intracellular Ca²⁺ concentration ([Ca²⁺]_i) and have an effect on vascular tone. In order to investigate the influence of diuretics on peripheral resistance in circulation, we investigated the alteration of [Ca²⁺]_i in testicular arterioles with respect to several categories of diuretics using real-time confocal laser scanning microscopy. In this study, hydrochlorothiazide (100 µM) and furosemide (100 µM) had no effect on the [Ca²⁺]_i dynamics. However, when spironolactone (300 µM) was applied, the [Ca²⁺]_i of smooth muscles increased. The response was considerably inhibited under either extracellular Ca²⁺-free conditions, the presence of Gd³⁺, or with a treatment of diltiazem. After the thapsigargin-induced depletion of internal Ca²⁺ store, the spironolactone-induced [Ca²⁺]_i dynamics was slightly inhibited. Therefore, the spironolactone-induced dynamics of [Ca²⁺]_i can be caused by either a Ca²⁺ influx from extracellular fluid or Ca²⁺ mobilization from internal Ca²⁺ store, with the former being dominant. As tetraethylammonium, an inhibitor of the K⁺ channel, slightly inhibited the spironolactone-induced [Ca²⁺]_i dynamics, the K⁺ channel might play a minor role in those dynamics. Tetrodotoxin, a neurotoxic Na⁺ channel blocker, had no effect, therefore the spironolactone-induced dynamics is a direct effect to smooth muscles, rather than an indirect effect via vessel nerves.