991 research outputs found

    Angiotensin II receptors and renin release in rat glomerular afferent arterioles

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    Angiotensin II receptors and renin release in rat glomerular afferent arterioles. The purpose of recent studies was to investigate the expression of angiotensin II (Ang II) receptor sites in afferent arterioles freshly isolated from the rat kidney, and the role of Ang II on renin release by these vessels. The method of isolation and purification of renal microves-sels was based on iron oxide infusion into the kidneys and separation of the afferent arterioles from glomeruli and connective tissue with the aid of a magnetic field, successive passages through various sieves, and harvesting with collagenase. Ang II receptor characteristics were evaluated by radioligand binding studies using the non-peptide Ang II antagonists of AT1 (Dup-753 and -532) and AT2 (PD-123319 and CGP-42112) receptors. AT1 antagonists displaced up to 80% of the Ang II binding with high affinity (3 nM), whereas the remaining 20% showed low affinity for the Dup compounds and CGP-42112 (>10 µM), and intermediate affinity for PD-123319 (12 µM). These data suggest the existence of two Ang II receptor subtypes in the renal vasculature of the rat. In separate experiments, renin release by isolated afferent arterioles in vitro was 9 ng/hr/mg under control conditions. Ang II (0.1 µM) inhibited renin secretion by 20%, whereas the adenylyl cyclase activator forskolin (10 µM) stimulated renin secretion by 50%. In arterioles isolated from rats chronically treated with a converting enzyme inhibitor (perindoprilate) to reduce endogenous formation of Ang II, renin release increased 20-fold under control conditions in vitro and was further stimulated by forskolin. These results demonstrate that this preparation is a useful tool to study the functional role of Ang II and the control of renin release in the afferent arterioles

    Angiotensin II receptors and renin release in rat glomerular afferent arterioles

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    Angiotensin II receptors and renin release in rat glomerular afferent arterioles. The purpose of recent studies was to investigate the expression of angiotensin II (Ang II) receptor sites in afferent arterioles freshly isolated from the rat kidney, and the role of Ang II on renin release by these vessels. The method of isolation and purification of renal microves-sels was based on iron oxide infusion into the kidneys and separation of the afferent arterioles from glomeruli and connective tissue with the aid of a magnetic field, successive passages through various sieves, and harvesting with collagenase. Ang II receptor characteristics were evaluated by radioligand binding studies using the non-peptide Ang II antagonists of AT1 (Dup-753 and -532) and AT2 (PD-123319 and CGP-42112) receptors. AT1 antagonists displaced up to 80% of the Ang II binding with high affinity (3 nM), whereas the remaining 20% showed low affinity for the Dup compounds and CGP-42112 (>10 µM), and intermediate affinity for PD-123319 (12 µM). These data suggest the existence of two Ang II receptor subtypes in the renal vasculature of the rat. In separate experiments, renin release by isolated afferent arterioles in vitro was 9 ng/hr/mg under control conditions. Ang II (0.1 µM) inhibited renin secretion by 20%, whereas the adenylyl cyclase activator forskolin (10 µM) stimulated renin secretion by 50%. In arterioles isolated from rats chronically treated with a converting enzyme inhibitor (perindoprilate) to reduce endogenous formation of Ang II, renin release increased 20-fold under control conditions in vitro and was further stimulated by forskolin. These results demonstrate that this preparation is a useful tool to study the functional role of Ang II and the control of renin release in the afferent arterioles

    The Study of Nitric Oxide Synthase Expression, Function, and Regulation in the Renal Vasculature During Postnatal Renal Development

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    The newborn kidney is vulnerable to vasomotor acute renal failure (ARF) from adverse perinatal events or complications of prematurity. Nitric oxide (NO) vasodilation is vitally protective in this type of ARF, but its relationship with other vasoactive factors, such as angiotensin II (AII) has not been examined. In the immature kidney, nitric oxide synthase (NOS) isoforms, specifically eNOS and nNOS, are developmentally regulated, but their specific role and regulation are unknown. The enhanced vasodilatory role of NO in the immature kidney was hypothesized to be attributed to regulatory, expressional, and functional differences in eNOS and nNOS isoforms from the adult. The objective of the dissertation was to: (1) determine which NOS isoform regulates immature renal hemodynamics by using functional whole animal studies utilizing intrarenal infusion of NOS inhibitors; (2) continue characterization of NOS expression in immature renal microstructures utilizing LCM (glomerular eNOS expression); (3) characterize expression and functional patterns of NOS isoforms, renin, and AT1 and AT2 receptors in immature preglomerular resistance microvessels utilizing novel microdissection techniques; and (4) determine AII regulation of NOS expression and function in the immature renal vasculature using AT1 and AT2 receptor inhibitors. Isoform specific inhibition demonstrated nNOS is the major NOS isoform regulating neonatal, but not adult, renal hemodynamics. nNOS expression, greatest in the newborn\u27s preglomerular resistance microvessels, decreased, while eNOS expression increased, with maturation. NOS enzymatic activity was greater in the neonate\u27s preglomerular resistance microvessels, than in the adult\u27s. AT1 and AT2 receptor inhibition demonstrated AII regulation of neonatal NOS expression and function via both receptors. Newborn nNOS expression demonstrated enhanced sensitivity to AII receptor inhibition. Dissertation conclusions include: nNOS is the major isoform regulating renal hemodynamics in the immature, but not the mature, kidney. Glomerular eNOS expression is developmentally regulated with differences between intracortical location of glomeruli. NOS enzymatic activity in preglomerular resistance microvessels is greater in the newborn, than in the adult, and may be due to upregulated nNOS expression. While AII regulates eNOS expression and NOS enzymatic activity, via AT1 and AT2 receptors, in newborn and adult preglomerular resistance microvessels, nNOS expression is regulated by AII only in the newborn

    Sympathetic innervation of the kidney in health and disease: Emphasis on the role of purinergic cotransmission

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    There is introductory information about non-synaptic transmission at sympathetic neuroeffector junctions and sympathetic nerve cotransmission utilizing noradrenaline and ATP as cotransmitters. Then the organzation and location of sympathetic nerves in different sites in the kidney are described, including renal arteries, juxtaglomerular arterioles and renal tubules. Sympathetic nervous control of glomerular filtration rate and of renin secretion are discussed. Evidence, obtained largely from experiments on animals, for sympathetic nerve modulation of the transport of water, sodium and other ions in the collecting duct of the nephron is described. Finally, there is coverage of the roles of sympathetic nerves in renal diseases, including hypertension, diabetes, hypothyroidism and ischaemia

    Adrenergic Control Of Renal Hemodynamics In Different Pathophysiological States With Renal Impairment : The Role Of 1-Adrenoceptor Subtypes [RC904. H995 2007 f rb].

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    Kajian ini menyelidik samada berlaku sebarang perubahan dalam populasi α1- adrenoseptor berfungsi dalam mengawalatur vasokonstriksi ginjal diaruh secara adrenergik di dalam model-model haiwan berpenyakit dengan kecacatan ginjal. This study investigated whether there is any alteration in the functional population of α1-adrenoceptors in mediating adrenergically induced renal vasoconstrictions in animal models of some pathological states characterized with renal impairment

    TGF-β type II receptor in rat renal vascular development: Localization to juxtaglomerular cells

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    TGF-γ type II receptor in rat renal vascular development: Localization to juxtaglomerular cells. To further define the role of transforming growth factor-beta (TGF-γ) receptors in renal vascular development, detailed immunohistochemical studies of TGF-γ receptor expression were performed from gestational day 15 through adulthood. On gestational day 15, TGF-γ type II receptor immunoreactivity was restricted to perirenal stromal and vascular cells. On gestational day 17 TGF-γ type II receptor immunoreactive stromal cells were observed within the kidney, with the same distribution as stromal α-smooth muscle actin and renin immunoreactive cells, and intense stromal TGF-γ type II receptor immunoreactivity continued through postnatal day 5. As vascular development progressed, TGF-γ type II receptor, α-smooth muscle actin and renin immunoreactivity became progressively restricted to small renal arteries and arterioles. Expression of TGF-γ type II receptors and renin was very intense in afferent glomerular arterioles during postnatal days 5 to 15, and then became progressively restricted only to juxtaglomerular cells in the mature kidney. TGF-γ type I receptor (ALK-5, ALK-1 and ALK-2) immunoreactivity was not detected in stromal or vascular elements during development or in the mature kidney. Intense TGF-γ type II receptor expression in renal stromal vascular smooth muscle cell precursors and developing blood vessels suggests a role for the TGF-γ type II receptors in the formation of the renal vascular smooth muscle compartment. The continued intense expression in juxtaglomerular cells argues for a role in renin synthesis and/or release. The absence of ALK-5, ALK-1, and ALK-2 in developing vascular smooth muscle and mature juxtaglomerular cells indicates that the canonical view of TGF-γ signaling may not hold in these locations

    Interaction Between The Renin Angiotensin System And A1-Adrenergic Receptors At The Renal Resistance Vessels In Diabetes Mellitus And Hypertension [QP572.A54 A288 2007 f rb].

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    α1-adrenoseptor dan reseptor subjenis angiotensin jenis 1 (AT1) memainkan peranan penting dalam pengawalaturan hemodinamik ginjal pada peringkat vaskulatur rintangan ginjal. α1-adrenoceptors and angiotensin type 1 (AT1) receptor subtype play important roles in the regulation of renal haemodynamic at the level of renal resistance vasculature. It is known that diabetes mellitus could damage the peripheral blood vessels and nerves, and is worsen by hypertensive state

    Angiotensin II and nitric oxide in chronic experimental nephritis

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    A Translational Study of the Correlation Between Low Birth Weight, Hypertension, and Kidney Function Using a Rat Model

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    We studied the correlation between low birth weight, hypertension, and kidney function using a rat model. There is a strong correlation between these three phenomena especially in the Southeastern United States and in non-White populations. We hypothesized that the anti-hypertensive drugs Reserpine and Hydralazine would prevent hypertension and improve renal function in low birth weight rats. We used a rat model created by Dr. Barbara Alexander in this study. Pregnant rats were subjected to Reduced Uterine Perfusion Pressure surgery. Silver clips were placed on the abdominal aorta and uterine arteries approximately two weeks after fertilization in order to restrict blood flow to the developing fetus. The reduced nutrient availability results in slower fetal development and low birth weight offspring. Two drugs with effects on cardiovascular function were used to lower blood pressure. Hydralazine was administered via drinking water at a dose of 80mg/L initiated at 6 weeks of age until the end experiment at 12 weeks of age. Reserpine was administered via drinking water at a dose of 5mg/L initiated at 6 weeks of age until the end of experiments at 12 weeks of age. Administration of this medication constituted the “treated” rats. At 12 weeks of age, catheters were inserted to measure blood pressure and glomerular filtration rate was calculated. Mild schemia reperfusion was performed to see how the kidneys reacted to mild stress. We found that the uterine restricted rats had normal gestations, but weighted significantly less than the controls at birth. The rats gained weight at the same rate and weighed the same at the end of the study. As expected, low birth weight untreated offspring had higher blood pressure than any other group. Surprisingly, GFR/g in the uterine-restricted, unstressed, untreated animals was not significantly higher, as predicted from both the higher MAP and presumably lower nephron number in these rats. Thus, there was no evidence of significant hyperfiltration occurring, and so this seemingly cannot explain the hypertension which developed. Based on this study, I would advocate using low birth weight as a biomarker for elevated risk of hypertension and kidney disease

    Localization of the succinate receptor in the distal nephron and its signaling in polarized MDCK cells

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    When the succinate receptor (SUCNR1) is activated in the afferent arterioles of the glomerulus it increases renin release and induces hypertension. To study its location in other nephron segments and its role in kidney function, we performed immunohistochemical analysis and found that SUCNR1 is located in the luminal membrane of macula densa cells of the juxtaglomerular apparatus in close proximity to renin-producing granular cells, the cortical thick ascending limb, and cortical and inner medullary collecting duct cells. In order to study its signaling, SUCNR1 was stably expressed in Madin-Darby Canine Kidney (MDCK) cells, where it localized to the apical membrane. Activation of the cells by succinate caused Gq and Gi-mediated intracellular calcium mobilization, transient phosphorylation of extracellular regulated kinase (ERK)1/2 and the release of arachidonic acid along with prostaglandins E2 and I2. Signaling was desensitized without receptor internalization but rapidly resensitized upon succinate removal. Immunohistochemical evidence of phosphorylated ERK1/2 was found in cortical collecting duct cells of wild type but not SUCNR1 knockout streptozotocin-induced diabetic mice, indicating in vivo relevance. Since urinary succinate concentrations in health and disease are in the activation range of the SUCNR1, this receptor can sense succinate in the luminal fluid. Our study suggests that changes in the luminal succinate concentration may regulate several aspects of renal function
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