PlGF, immune system and hypertension

The huge diffusion of hypertension and its associated complications has a significant impact on public health [1]. However, despite the high prevalence of essential hypertension and many efforts of research, the basic pathophysiological causes remain puzzling

Correction to the pathogenic alternative splicing, caused by the common GNB3 c.825C>T allele, using a novel, antisense morpholino

The very common GNB3 c.825C>T polymorphism (rs5443), is present in approximately half of all human chromosomes. Significantly the presence of the GNB3 825T allele has been strongly associated, with predisposition to essential hypertension. Paradoxically the presence of the GNB3 825T allele, in exon 10, introduces a pathogenic alternative RNA splice site into the middle of exon 9. To attempt to correct this pathogenic aberrant splicing, we therefore bioinformatically designed, using a Gene Tools® algorithm, a GNB3 specific, antisense morpholino. It was hoped that this morpholino would behave in vitro as either a potential “ splice blocker and/or exon skipper, to both bind and inhibit/reduce the aberrant splicing of the GNB3, 825T allele. On transfecting a human lymphoblast cell line homozygous for the 825T allele, with this antisense morpholino, we encouragingly observed both a significant reduction (from ~58% to ~5%) in the production of the aberrant smaller GNB3 transcript, and a subsequent increase in the normal GNB3 transcript (from ~42% to ~95%). Our results demonstrate the potential use of a GNB3 specific antisense morpholino, as a pharmacogenetic therapy for essential hypertension

Endothelial Dysfunction in Human Essential Hypertension

Although the endothelium has a number of important functions, the term endothelial dysfunction is commonly used to describe impairment in its vasodilatory capacity. It is increasingly recognized that this is related to hypertension, although whether it predates essential hypertension or is a consequence of it is still unknown. In this review, we explore the mechanisms of endothelial dysfunction in essential hypertension, its prognostic significance and methods of pharmacological reversal

Changes in kidney function in a population with essential hypertension in real life settings

Introduction. Hypertension has been identified as one of the commonest modifiable determinants for chronic kidney disease progression. A variety of antihypertensive drugs are available and their effect on kidney function has been investigated by a large number of randomized controlled trials. Observational studies, although scarcely been used, outpatient can reflect everyday practice, where drug exposures vary over time, and may provide an alternative for detecting longitudinal changes in kidney function. Materials and Methods. We applied mixed model repeated measures analysis to investigate the effect of antihypertensive drug categories and their combinations on kidney function change over time in a cohort of 779 patients with essential hypertension, using the data from a Greek hypertension outpatient clinic. Antihypertensive drugs were grouped in 5 categories. Their effect was evaluated and their combinations with and without renin-angiotensin-system inhibitors (RASI) to each other. In addition, the combination of RASI with calcium channel blockers (CCBs) was studied. Results. Diuretics, RASI, CCBs, and beta-blockers had a significant renoprotective and blood pressure lowering effect. Combinations with RASI had a smaller beneficial effect on kidney function compared to CCBs (0.75 mL/min/1.73 m2 per year of drug use versus 0.97 mL/min/1.73 m2). There was no additional effect when combining RASI with CCBs. However, the lowering effect on systolic blood pressure was greater (-0.83 mm Hg per year of drug use, P < .001). Conclusions. RASI were found to have a smaller, although significant, renoprotective effect. There was no additional effect on kidney function when combining RASI with CCBs

Enzyme-linked immunosorbent assay for urinary albumin at low concentrations

We describe an enzyme-linked immunosorbent assay (ELISA) for urinary albumin. It requires only commercially available reagents, can detect as little as 16 micrograms of albumin per liter, and analytical recovery ranges from 92 to 116%. The assay is simple, rapid, and inexpensive. Albumin excretion was 6.2 (SD 4.1) mg/24 h in healthy subjects (n = 40), 14.7 (SD 7.2) mg/24 h in albumin-test-strip-negative Type I diabetics (n = 11), and 19.7 (SD 16.2) mg/24 h in patients with essential hypertension (n = 12)

Transdermal β-Blocker Therapy in Essential Hypertension

Transdermal drug delivery has been applied to various agents in an effort to decrease the frequency of drug administration and increase the patients compliance. In our study, we demonstrated that transdermal application of a ß-blocker (20 mg mepindolol) in patients with essential hypertension led to effective blood pressure lowering effect within 1 week (160.1 ±6.1 mm Hg/95.8 ± 8.3 mm Hg vs 136.8 ± 7.2 mm Hg/84.3 ± 5.0 mm Hg; Ρ < 0.05). A controlled study of transdermal versus oral ß-blocker administration in hypertensives is necessary before this new therapeutic system is introduced in antihypertensive treatment. Am J Hypertens 1988; 1:199S-200

Association between one-hour post-load plasma glucose levels and vascular stiffness in essential hypertension

Objectives: Pulse wave velocity (PWV) is a surrogate end-point for cardiovascular morbidity and mortality. A plasma glucose value $155 mg/dl for the 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high-risk for type-2 diabetes (T2D) and for subclinical organ damage. Thus, we addressed the question if 1-hour post-load plasma glucose levels, affects PWV and its central hemodynamic correlates, as augmentation pressure (AP) and augmentation index (AI). Methods: We enrolled 584 newly diagnosed hypertensives. All patients underwent OGTT and measurements of PWV, AP and AI. Insulin sensitivity was assessed by Matsuda-index. Results: Among participants, 424 were NGT and 160 had impaired glucose tolerance (IGT). Of 424 NGT, 278 had 1-h postload plasma glucose ,155 mg/dl (NGT,155) and 146 had 1-h post-load plasma glucose$155 mg/dl (NGT$155). NGT$155 had a worse insulin sensitivity and higher hs-CRP than NGT,155, similar to IGT subjects. In addition, NGT $155 in comparison with NGT,155 had higher central systolic blood pressure (134612 vs 131610 mmHg), as well as PWV (8.463.7 vs 6.761.7 m/s), AP (12.567.1 vs 9.865.7 mmHg) and AI (29.4611.9 vs 25.1612.4 regression analysis, 1-h post-load plasma glucose resulted the major determinant of all indices of vascular stiffness. Conclusion: Hypertensive NGT$155 subjects, compared with NGT,155, have higher PWV and its hemodynamic correlates that increase their cardiovascular risk profile

Towards precision medicine for hypertension: a review of genomic, epigenomic, and microbiomic effects on blood pressure in experimental rat models and humans

Compelling evidence for the inherited nature of essential hypertension has led to extensive research in rats and humans. Rats have served as the primary model for research on the genetics of hypertension resulting in identification of genomic regions that are causally associated with hypertension. In more recent times, genome-wide studies in humans have also begun to improve our understanding of the inheritance of polygenic forms of hypertension. Based on the chronological progression of research into the genetics of hypertension as the "structural backbone," this review catalogs and discusses the rat and human genetic elements mapped and implicated in blood pressure regulation. Furthermore, the knowledge gained from these genetic studies that provide evidence to suggest that much of the genetic influence on hypertension residing within noncoding elements of our DNA and operating through pervasive epistasis or gene-gene interactions is highlighted. Lastly, perspectives on current thinking that the more complex "triad" of the genome, epigenome, and the microbiome operating to influence the inheritance of hypertension, is documented. Overall, the collective knowledge gained from rats and humans is disappointing in the sense that major hypertension-causing genes as targets for clinical management of essential hypertension may not be a clinical reality. On the other hand, the realization that the polygenic nature of hypertension prevents any single locus from being a relevant clinical target for all humans directs future studies on the genetics of hypertension towards an individualized genomic approach