The glomerular origin of essential hypertension

Rosenberg, Warren

doi:10.1016/0306-9877(83)90019-1

Cited by 8 publications

(3 citation statements)

References 12 publications

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“…By contrast, it is the superficial glomeruli in BPH/2 mice that show reduced permeability of the basement membrane compared with BPN/3 mice but not the juxtamedullary glomeruli. Theoretically, reduced filtration surface and permeability could lead to decreased glomerular filtration rate, volume expansion, and hypertension (Rosenberg, 1983). However, glomerular filtration rate was shown to be less in juvenile BPH/2 mice than in mature BPH/2 mice (Rosenberg et al, 1985).…”

Section: Heart Vessel and Kidney Structure And Functionmentioning

confidence: 99%

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

et al. 2019

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It has been 45 years since Gunther Schlager used a cross breeding program in mice to develop inbred strains with high, normal, and low blood pressure (BPH/2, BPN/3, and BPL/1 respectively). Thus, it is timely to gather together the studies that have characterized and explored the mechanisms associated with the hypertension to take stock of exactly what is known and what remains to be determined. Growing evidence supports the notion that the mechanism of hypertension in BPH/2 mice is predominantly neurogenic with some of the early studies showing aberrant brain noradrenaline levels in BPH/2 compared with BPN/3. Analysis of the adrenal gland using microarray suggested an association with the activity of the sympathetic nervous system. Indeed, in support of this, there is a larger depressor response to ganglion blockade, which reduced blood pressure in BPH/2 mice to the same level as BPN/3 mice. Greater renal tyrosine hydroxylase staining and greater renal noradrenaline levels in BPH/2 mice suggest sympathetic hyperinnervation of the kidney. Renal denervation markedly reduced the blood pressure in BPH/2 but not BPN/3 mice, confirming the importance of renal sympathetic nervous activity contributing to the hypertension. Further, there is an important contribution to the hypertension from miR-181a and renal renin in this strain. BPH/2 mice also display greater neuronal activity of amygdalo-hypothalamic cardiovascular regulatory regions. Lesions of the medial nucleus of the amygdala reduced the hypertension in BPH/2 mice and abolished the strain difference in the effect of ganglion blockade, suggesting a sympathetic mechanism. Further studies suggest that aberrant GABAergic inhibition may play a role since BPH/2 mice have low GABAA receptor δ, α4 and β2 subunit mRNA expression in the hypothalamus, which are predominantly involved in promoting tonic neuronal inhibition. Allopregnanolone, an allosteric modulator of GABAA receptors, which increase the expression of these subunits in the amygdala and hypothalamus, is shown to reduce the hypertension and sympathetic nervous system contribution in BPH/2 mice. Thus far, evidence suggests that BPH/2 mice have aberrant GABAergic inhibition, which drives neuronal overactivity within amygdalo-hypothalamic brain regions. This overactivity is responsible for the greater sympathetic contribution to the hypertension in BPH/2 mice, thus making this an ideal model of neurogenic hypertension.

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Section: Heart Vessel and Kidney Structure And Functionmentioning

confidence: 99%

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

et al. 2019

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“…Abnormalities of intrarenal hemodynamics have been hypothesized to play a pivotal role in the pathogenesis of essential hypertension [14,15]. On the other hand, changes in renal hemodynamics and in its regulation have been found even in the early stages of the disease [14,[16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Microalbuminuria Fractional Clearance and Early Renal Permselectivity Changes in Essential Hypertension

Cottone

Cerasola²

1992

Am J Nephrol

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In order to verify if, in essential hypertension (EH), the microalbuminuria (AER) increase could be due to hemodynamic modifications or to glomerular structural changes, in 15 essential hypertensives (EHs) with 24-hour AER > 16 µg/min and in 15 EHs with 24-hour AER ≤ 16 µg/min, the day- and nighttime behavior of creatinine clearance (Ccr), as well as AER clearance (AER-C) and fractional clearance (AER-FC), and behavior of blood pressure (BP) was evaluated. Patients with 24-hour AER > 16 µg/min showed significantly higher values of 24-hour and daytime Ccr than the other group of EHs, while during the night period, there were no significant differences between the two groups. On the contrary, AER and both AER-C and AER-FC resulted markedly and significantly higher in the EHs with 24-hour AER > 16 µg/min not only in the 24-hour evaluation, but also during the nighttime study, notwithstanding the significant decrease in BP and in Ccr observed during the night. These data, in the absence of correlations between BP and AER-FC seem to demonstrate the existence in EHs with 24-hour AER > 16 µg/min of an altered glomerular permselectivity, due to changes of the glomerular membrane.

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“…[2][3][4] It has been proposed that renal vascular changes may not simply be a complication but the cause for blood pressure elevation and thus may play a pivotal role in the pathogenesis of essential hypertension. 5 In the search for mechanisms by which genetic markers contribute to the development of hypertension, recent interest focused on a novel gene polymorphism closely associated with a wellestablished intermediate phenotype, that is, the enhanced Na ϩ /H ϩ exchanger activity in hypertensive subjects. 6 Immortalized lymphoblasts of these patients have been found to respond with enhanced G-protein activation on stimulation.…”

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confidence: 99%

G-Protein β ₃ Subunit Gene (GNB3) 825T Allele Is Associated With Enhanced Renal Perfusion in Early Hypertension

et al. 2001

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Abstract-The C825T polymorphism of the gene encoding the G-protein ␤ 3 subunit (GNB3) is associated with increased intracellular signal transduction and arterial hypertension. The aim of the study was to investigate the impact of this polymorphism on early adaptive processes of the left ventricle and renal hemodynamic changes in young normotensive to mildly hypertensive subjects. Ninety-five white male students with normal or mildly elevated blood pressure were genotyped for the GNB3 C825T polymorphism. In each participant, 24-hour ambulatory blood pressure, left ventricular structure and function (2D-guided M-mode echocardiography), renal plasma flow (para-aminohippurate clearance), glomerular filtration rate (inulin clearance), and 24-hour urinary sodium excretion were determined. The GNB3 825T allele was not associated with casual or ambulatory blood pressure, parameters of left ventricular structure or function, glomerular filtration, or 24-hour urinary sodium excretion. However, in T-allele carriers (CTϩTT), renal plasma flow was higher than in CC subjects (CT/TT: 659Ϯ96 versus CC: 614Ϯ91 mL/min, Pϭ0.019). ANOVA disclosed that renal plasma flow was independently influenced by both genotype and blood pressure, with hypertensives having a higher renal plasma flow than normotensive subjects. This was the fact irrespective of the criteria used for the definition of hypertension (World Health Organization or 24-hour ambulatory blood pressure criteria). The GNB3 825T variant is associated with increased renal perfusion in this study. Because early renal hemodynamic changes play a pivotal role in the pathogenesis of essential hypertension, our data suggest a relevance of increased G-protein activation in the pathogenesis of hypertension. Key Words: G proteins Ⅲ polymorphism Ⅲ genes Ⅲ hypertension, essential Ⅲ hemodynamics T he early course of essential hypertension is characterized by structural and functional changes in the systemic and renal circulation. In addition, early structural changes of the left ventricle (LV) have been reported. Increased concentric remodeling of the LV and impaired diastolic function have been recognized to reflect early changes of the myocardium in early essential hypertension. 1 Renal hemodynamics were shown to be abnormally regulated in a prehypertensive stage, and increased renal perfusion was reported in early hypertension. [2][3][4] It has been proposed that renal vascular changes may not simply be a complication but the cause for blood pressure elevation and thus may play a pivotal role in the pathogenesis of essential hypertension. 5 In the search for mechanisms by which genetic markers contribute to the development of hypertension, recent interest focused on a novel gene polymorphism closely associated with a wellestablished intermediate phenotype, that is, the enhanced Na ϩ /H ϩ exchanger activity in hypertensive subjects. 6 Immortalized lymphoblasts of these patients have been found to respond with enhanced G-protein activation on stimulation. 7 Subsequently, a single nucleo...

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The glomerular origin of essential hypertension

Cited by 8 publications

References 12 publications

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

Microalbuminuria Fractional Clearance and Early Renal Permselectivity Changes in Essential Hypertension

G-Protein β ₃ Subunit Gene (GNB3) 825T Allele Is Associated With Enhanced Renal Perfusion in Early Hypertension

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The glomerular origin of essential hypertension

Cited by 8 publications

References 12 publications

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

Microalbuminuria Fractional Clearance and Early Renal Permselectivity Changes in Essential Hypertension

G-Protein β 3 Subunit Gene (GNB3) 825T Allele Is Associated With Enhanced Renal Perfusion in Early Hypertension

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G-Protein β ₃ Subunit Gene (GNB3) 825T Allele Is Associated With Enhanced Renal Perfusion in Early Hypertension