ACE inhibition has adverse renal effects during dietary sodium restriction in proteinuric and healthy rats

Angiotensin-converting enzyme inhibitors (ACEi) provide renoprotection. A low sodium diet enhances their efficacy. However, the added effect of sodium restriction on proteinuria and blood pressure is not invariably associated with better preservation of renal morphology, suggesting that the combination of ACEi with a low sodium diet can elicit renal structural abnormalities. To test this hypothesis, the effects of ACEi in combination with a control (CS) or a low sodium (LS) diet were investigated in healthy rats and in adriamycin nephrotic rats. After 3 weeks of treatment, rats were sacrificed and kidneys examined for renal structural abnormalities. In healthy rats, ACEi reduced blood pressure: the fall in blood pressure was significantly greater in the ACEi/LS group. Renal morphology was normal in the ACEi/CS group but severe interstitial damage was found in the ACEi/LS group. This was associated with increased interstitial macrophage influx and up-regulation of osteopontin, alpha-smooth muscle actin, and collagen III expression. In addition, ACEi/LS induced an increase in the total medial area of afferent arterioles. In nephrotic rats, ACEi/LS reduced both blood pressure and proteinuria, whereas only blood pressure was reduced in the ACEi/CS group. Mild interstitial damage was present in the ACEi/CS group but, strikingly, pronounced tubulo-interstitial abnormalities occurred in the ACEi/LS group, similar to those seen in ACEi/LS healthy rats, with similar changes in afferent arteriolar walls. In conclusion, the combination of ACEi/LS elicits pronounced renal interstitial abnormalities in healthy and nephrotic rats, despite a significant reduction of proteinuria in the latter. Considering their occurrence in healthy rats, these renal adverse effects cannot be due to specific characteristics of adriamycin nephrosis. Further studies should elucidate the mechanisms underlying these observations and their impact on long-term renoprotection.     

Retinal arterioles have impaired reactivity to hyperoxia in type 1 diabetes

Purpose: Diabetes has adverse effects on the retinal microvasculature. The purpose of this study was to compare the effects of inhalation of hypoxic, hyperoxic and normoxic–hypercapnic gas mixtures on retinal vessel diameter in people with and without diabetes. Methods: Sixty‐one participants (aged 24–50 years) 29 with (male : female ratio 2.6 : 1) and 32 without (male : female ratio 0.7 : 1) diabetes, inhaled hypoxic, hyperoxic and normoxic–hypercapnic gas mixtures for 3–5 mins. The diameters of arterioles and venules were measured using digital retinal images taken before and after gas inhalation. Results: There was no significant difference in the diameters of arterioles and venules prior to gas inhalation in people with and without diabetes. Inhalation of the hyperoxic gas mixture caused a statistically significant decrease in arteriolar and venular diameters without altering mean arterial pressure significantly. Arteriolar vasoconstriction in response to the hyperoxic gas mixture was significantly reduced in people with diabetes (3.95% versus 7.75%; p = 0.04), but venular vasoconstriction did not differ significantly. A hypoxic gas mixture caused increased arteriolar and venular diameter and a normoxic–hypercapnic gas mixture had no significant effect on vessel diameter. Responses to hypoxic and normoxic–hypercapnic gas did not differ significantly between diabetes and non‐diabetes subjects. Conclusions: Type 1 diabetes impairs retinal arteriolar responses to hyperoxia. Abnormalities in retinal arteriolar reactivity in response to oxygen may play a role in the development of diabetic retinopathy and this technique may represent a simple means of identifying early abnormalities in the reactivity of retinal arterioles in diabetes.     

不同年龄自发性高血压大鼠肾内小动脉的形态学重建

目的:探讨高血压大鼠年龄、高血压持续时间与肾内小动脉形态学重建的关系。方法:16,26,40和55周自发性高血压大鼠（SHR）,使肾内小动脉处于最大舒张状态后,在肾组织切片上用光镜配合计算机图像分析法观测肾内小动脉的几何形态。结果:与同龄正常血压大鼠(Wistar-Kyoto,WKY)相比,4个年龄组SHR肾内小动脉的壁厚、壁厚内径比都显著增大;外径在50-200 μm间的小动脉还伴有壁面积的增加;40和55周SHR外径在20-50 μm间的小动脉内径减小。肾内小动脉的形态学改变与年龄和高血压状态有关。结论:高血压是16-55周龄SHR肾内小动脉重建的主要因素,外径在50 μm以下的肾内小动脉的重建以中膜平滑肌细胞的重排为主,外径在50 μm以上的肾内小动脉的重建则存在中膜平滑肌细胞的增殖。     

IMPACT OF CYCLO-OXYGENASE BLOCKADE ON JUXTAMEDULLARY MICROVASCULAR RESPONSES TO ANGIOTENSIN II IN RAT KIDNEY

1. Experiments were designed to evaluate the hypothesis that cyclo-oxygenase products modulate the influence of angiotensin II (AII) on the renal juxtamedullary microvasculature of enalaprilat-treated rats. 2. The in vitro blood-perfused juxtamedullary nephron technique was utilized to provide access to afferent arterioles, efferent arterioles and descending vasa recta located in the outer stripe of the outer medulla. 3. Baseline afferent arteriolar diameter was 20.8 ± 1.9 μm in kidneys subjected to cyclo-oxygenase blockade (1μmol/L piroxicam), a value significantly lower than that observed in untreated kidneys (26.1 ± 1.0 μm). Baseline diameters of efferent arterioles and outer medullary descending vasa recta did not differ between untreated and piroxicam-treated groups. 4. Topical application of 1 nmol/L AII reduced blood flow through outer medullary descending vasa recta by 22 ± 6% in untreated kidneys and by 24 ± 7% in piroxicam-treated kidneys. 5. In untreated kidneys, AII (0.01–100nmol/L) produced concentration-dependent afferent and efferent arteriolar constrictor responses of similar magnitudes. Neither afferent nor efferent arteriolar AII responsiveness was significantly altered in piroxicam-treated kidneys, although afferent responses exceeded efferent responses at AII concentrations ≥ 10 nmol/L. 6. We conclude that endogenous cyclo-oxygenase products exert a vasodilator influence on juxtamedullary afferent arterioles under baseline conditions. Although cyclo-oxygenase inhibition had little effect on juxtamedullary microvascular responses to AII, the response to high AII concentrations may be modulated by cyclo-oxygenase products in a manner which delicately alters the relative influence of the peptide on pre- vs postglomerular resistances.     

Relationship among the reaction of the systemic arterial pressure,constriction of skeletal muscle arterioles,and norepinephrine-induced changes in the linear blood flow rate in rats subjected to whole-body γ-irradiation in a dose of 1 gy

The duration and amplitude of pressor reactions of AP to intravenous injection of norepinephrine remain unchanged 1, 3 and 5–6 days after irradiation. The duration of norepinephrine-induced changes in the diameter of arterioles of the thumb extensor muscle proper and the linear blood flow rate in them is decreased in irradiated animals. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 3, pp. 274–277, March, 1994     

PREVENTION OF STRUCTURAL ARTERIOLAR CHANGES IN DOCA HYPERTENSION WITH HYDRALLAZINE

Structural changes in resistance vessels were studied by (a) hindquarter perfusion; and (b) planimetry of cross-sections of renal arterioles in uninephrectomized rats treated for 10 weeks with saline and either DOCA (deoxycorticosterone acetate), DOCA plus hydrallazine, vehicle plus hydrallazine or vehicle only. DOCA-treated rats developed hypertension and structural change. Addition of hydrallazine prevented both hypertension and the development of structural change. Structural arteriolar change in DOCA/salt hypertension is related to the high blood pressure or a closely associated factor rather than some other effect of DOCA.     

Integrins and regulation of the microcirculation: from arterioles to molecular studies using atomic force microscopy

Integrins are an important class of receptors for extracellular matrix proteins that can mediate both force transmission, by virtue of their connections with the cell matrix and cytoskeleton; and signal transduction, resulting from the assemblages of signaling proteins that associate with focal contacts. Consequently, integrins have been proposed to be the mechanosensor in vascular smooth muscle and endothelial cells and to play a central role in mechanotransduction. In this regard, mechanical force is an important stimulus for many vascular functions, including contractile and relaxation processes,proliferation, migration, attachment, and cell phenotype determination. Collectively, these functions define physiological properties of the vasculature such as control of blood flow, capillary pressure,permeability, and peripheral vascular resistance, and play a role in pathophysiological processes like hypertension, diabetes, and arteriosclerosis. Our knowledge concerning how integrins sense and transduce physical forces into cellular signals and which integrins are involved is incomplete. Compared to other cell surface receptors, integrins have a relatively low affinity for their binding sites on the extracellular matrix and their affinity can be regulated. These characteristics of integrin-ligand interaction may facilitate dynamic processes such as cell migration, cell remodeling, and contractile activation in response to external forces. Important questions remain concerning the nature and origin of integrin-mediated signaling in the vascular wall.     

Role of tissue hypoxia in cerebrovascular regulation: a mathematical modeling study

This paper presents a mathematical model of cerebrovascular regulation, in which emphasis is given to the role of tissue hypoxia on cerebral blood flow (CBF). In the model, three different mechanisms are assumed to work on smooth muscle tension at the level of large and small pial arteries: CO₂reactivity, tissue hypoxia, and a third mechanism necessary to provide good reproduction of autoregulation to cerebral perfusion pressure (CPP) changes. Using a single set of parameters for the mechanism gains, assigned via a best fitting procedure, the model is able to reproduce the pattern of pial artery caliber and CBF under a large variety of physiological stimuli, either acting separately (hypoxia, CPP changes, CO₂ pressure changes) or in combination (hypercapnia+hypoxia; hypercapnia+hypotension). Furthermore, the model can explain the increase in CBF and the vasoconstriction of small pial arteries observed experimentally during hemodilution, ascribing it to the decrease in blood viscosity and to the antagonistic action of the flow-dependent mechanism (responsible for vasoconstriction) and of hypoxia (responsible for vasodilation). Finally, the interaction between hypoxia and intracranial pressure (ICP) has been analyzed. This interaction turns out quite complex, leading to different ICP time patterns depending on the status of the cerebrospinal fluid outflow pathways and of intracranial compliance. © 2001 Biomedical Engineering Society. PAC01: 8719Uv, 8719Tt, 8719Ff, 8380Lz     

IgA肾病患者肾小动脉病变与临床及病理特点的相关性

目的探讨IgA肾病患者肾小动脉病变与临床、病理的相关性。方法 60例IgA肾病患者,根据肾小动脉病变程度分为未见明显病理改变组(A组,25例)、肾小动脉增厚组(B组,31例)和肾小动脉增厚伴透明样变组(C组,4例),分析三组肾小动脉病变程度与其临床指标及病理学参数的相关性。结果三组肾小动脉病变程度与血肌酐水平(P<0.01)、血尿酸(P<0.05)、收缩压(P<0.05)、舒张压(P<0.05)呈明显正相关。三组肾小动脉病变程度与内皮细胞增生指数(P<0.01)、系膜细胞增生指数(P<0.05)、肾小球慢性化指数(P<0.01)、间质炎症指数(P<0.01)、肾小管萎缩纤维化指数(P<0.05)呈明显正相关。结论肾小动脉病变在IgA肾病中病情评估中有重要作用,可作为预测肾脏预后的指标之一。