Recent advances in hypertension research

Raised blood pressure affects 1.13 billion people worldwide according to Global Health Observatory (GHO) data.1 Interestingly, according to WHO statistics, the prevalence of elevated blood pressure depends on World Bank income group. Data for the years between 1975 and 2015 are shown in Figure 1. The change over the last 40 years might be because of better awareness and better treatment options in regions with higher income whereas the prevalence has increased in the low-income regions. Currently, a high percentage of patients have suboptimal or inadequately controlled blood pressure, thus placing them at risk for cardiovascular disease.2 Hypertension is associated with a number of co-morbidities.3 There is an agreement that arterial hypertension is a risk factor for cardiovascular events such as myocardial infarction and stroke; however, Khnaji et al conclude from a systematic review of guidelines that considerable discrepancies in cardiovascular screening guidelines still exist, with no consensus on optimum screening strategies or treatment threshold.4 Recently, in Acta Physiologica, a number of articles have been published that are dedicated to basic mechanisms of blood pressure regulation such as in the kidney for example.5 The kidney is involved in the long-term regulation of blood pressure. The exact mechanism of how the endothelium is involved in the regulation of vascular tone is still unknown. Brasen et al6 investigated the role of the vascular gap junctions and potassium channels in renal endothelial-derived hyperpolarization. For this purpose, the authors investigated the role of small and intermediate conductance potassium channels in connexin40 knockout mice and their respective controls. In addition to direct measurements of electrical parameters, the authors applied mathematical modelling to interpret their results. The authors measured the relative relaxation at different acetylcholine levels. The authors hence conclude from their results that renal endothelial hyperpolarization is initiated by activation of small and intermediate conductance potassium channels. The model shows that hyperpolarization can spread through myoendothelial gap junctions. The reduced coupling in the connexin40 knockout mice enhances the role of released potassium in the signalling process.6 In 1998, the Nobel Prize in Physiology or Medicine was awarded to Robert F. Furchgott, Louis J. Ignarro and Ferid Murad for their discoveries concerning “nitric oxide as a signalling molecule in the cardiovascular system” (https://www.nobelprize.org/prizes/medicine/1998/press-release/). It is not surprising that a number of articles in Acta Physiologica are dedicated to nitric oxide such as the following examples. Intake of inorganic nitrate, which is predominantly found in green leafy vegetables and beets, has a variety of favourable cardiovascular effects, and the mechanisms underlying blood pressure reduction by dietary inorganic nitrate are reviewed by Carlstrom et al in Acta Physiologica.7 In this review, the reader will get detailed insights about the signalling pathways of inorganic nitrate. The afferent arterioles in the kidney connecting to the filtration site, the glomerulus, play an important role in the in the regulation of renal blood flow and glomerular filtration rate and are involved in long-term blood pressure regulation. Gao et al8 investigated the influence of albumin concentration on the contractile responses of the afferent arterioles. In a number of sophisticated experiments, the authors investigated the action of Angiotensin II in various combinations with different albumin concentrations on the diameter of afferent arterioles. To get some insight about the signalling, the authors applied DAF-FM fluorescence measurements to quantify the NO release. The authors conclude that the albumin-induced modulation of the tone of the afferent arterioles is mediated by the increased osmolarity and nitric oxide scavenging. According to the law of Hagen and Poiseuille, a small change in vessel diameter has a tremendous impact on resistance and eventually on perfusion and blood pressure, ie, the regulation of vessel diameter is of great interest. Phosphorylation is a general principle in signalling by which proteins may be modified by kinases or phosphatases and as a result, show altered catalytic activities. This principle is part of the focus of the scientific investigations in the next publications. The work of Mochalov et al9 investigates the role of Rho-kinase activity on Ca2+ sensitivity of arterial contraction in an age-dependent model. The authors use a broad spectrum of methods such as tension measurements, Ca2+-fluorimeter, pharmacological interventions, quantitative phospho-protein analysis, heart rate and blood pressure measurements in the animal model. The authors conclude that the Rho-kinase activity is the main modulator of Ca2+-sensitivity that changes with age. Interestingly, this relationship leads to modified adrenergic arterial pressure responses.9 In the work of Lubomirov,10 the role of phosphorylation of MYPT1 and related isoforms are involved in cGMP sensitivity in arteries. The authors apply a number of pharmacological interventions, force measurements and methods of protein biochemistry to address this question. The authors conclude that phosphorylation at two specific sites of the MYPT1 are important in the regulation of intrinsic contractile activity in cerebral arteries. Perivascular adipose tissue has been recognized unequivocally as a major player in the pathology of metabolic and cardiovascular diseases.11 A further piece of the puzzle has been added by the work of Donovan et al12 By measuring the contraction responses of coronary arteries in various intervention studies with and without perivascular adipose tissue, they were able to pinpoint a mechanism involving hydrogen sulphide and cystathionine-β-synthase. The authors conclude that the perivascular adipose tissue augments hypoxic relaxation through H2S and cystathionine-β-synthase which might be important in the regulation of coronary blood flow during hypoxia.12 The heart as the engine of convection in our body is the main focus for many investigations in Acta Physiologica. In an interesting study by Yeves et al,13 the authors identify the sodium/proton exchanger-1 (NHE-1) as a key target of IGF-1. In their study, the authors measure the NHE-1 activity, expression, and phosphorylation, as well as other biochemical parameters such as poperoxide production, as well as activity of superoxide dismutase and contractility of hearts of spontaneously hypertensive, and Wistar rats depending on IGF-1. The authors conclude that IGF-1 imposes a cardio protective role in the context of NHE-1 inhibition and resulting antioxidant effects.13 Aortic stenosis leads to left ventricular hypertrophy with potential further complications such as impaired coronary haemodynamics.14 The treatment of the stenosis might involve valve replacements. In a study by Broyd et al that involves non-invasive wave intensity measurements of coronary haemodynamics, the authors aim to measure the sequential effects of outflow tract obstruction relief and then left ventricular hypertrophy regression following intervention for aortic stenosis. Wave intensity analysis is a rather specific art form that involves complicated looking formulas of differential equations. The authors conclude from their hemodynamic analysis that the hypertrophy regression contributes an additional benefit that might be part of an improvement in prognosis of this condition.14 To get insight into a particular question, thinking outside the box might be helpful. This is what Poulsen et al15 did by approaching the question as to whether or not arterial blood pressure scales with body mass. Baes on their intensive meta-analysis of literature data of 47 species, they conclude that the existing literature does not provide evidence for a scaling of arterial blood pressure and body mass across the analysed taxa.15 In an interesting review about storage of sodium in the interstitium, Wiig et al16 highlight the role of this compartment in the volume and blood pressure homeostasis. The role of the endothelium in the microcirculation was highlighted by an review by Rosenblum.17 Inducible knock out models have been proven to be a valuable tool in cardiovascular research. In a work by Schreier et al,18 the role of a deletion of the epidermal growth factor (EGF) receptor in vascular smooth muscle cells is investigated in detail. In the work, the authors evaluate the relevance of this protein during chronic angiotensin II challenge. The authors measure body weight, water intake, food intake and tibia length in the animals. Further, they evaluate the expression of a number of genes related to fibrotic reactions and measure aortic media thickness as well as dynamic parameters such as potassium-induced constriction of the arteries. The authors conclude from their results that vascular smooth muscle cell-EGFRs are relevant for pathological angiotensin II action in vivo with respect to renal end-organ damage.18 Sympathetic nerve activity modulates arterial blood pressure. In an interesting experimental study by Fan et al,19 the authors investigate the role of the neuropeptide orexin A in the signalling of the paraventricular nucleus (PVN) in the brain with respect to sympathetic activity. The authors find that after microinjection of orexin into the PVN the sympathetic activity is increased as determined by nerve activity measurements. The authors explain this by the involvement of pro-inflammatory cytokines. Interestingly, the increase in pro-inflammatory cytokines as determined by quantitative polymerase chain reaction was blocked by curcumin which is widely used in food production worldwide. Despite the advances in recent years in the field of treatment of hypertension, the condition can be regarded a global health challenge that requires both, intensive basic research as well as measures of public health to reduce the burden on mankind. None.