Arterial hypertension

Blood pressure is an important determinant in the progression of many cardiovascular and renal diseases. The interest of the physiologists in this topic is reflected in the high number of articles that appeared in Acta Physiologica recently. About 20% of the articles in Acta Physiologica contain the keyword blood pressure or hypertension in the year 2016. According to the semantic analysis website gopubmed.org, the term pressure is top rating among all semantic “concepts” in Acta Physiologica if one looks at the years 2014–2016. First epidemiological observations between a possible connection of body fat and arterial blood pressure (BP)1 have stimulated the search for fat-derived substances2 that may interfere with blood pressure regulation such as baroreflex control.3 Only recently, the visceral adipose tissue-derived serine protease inhibitor (vaspin) was investigated that according to recent research augments, the nitric oxide mediated endothelium-dependent relaxation by inhibiting the acetylcholine esterase activity in mesenteric arteries.4 This protease inhibitor (vaspin) has an chronic effect on blood pressure when given to rats for 4 weeks.5 The long-term effects of vaspin on blood pressure relate possibly to antioxidative and anti-inflammatory mechanisms triggered by the protease.5 The potential therapeutic benefits of the insulin-like growth factor 1 (IGF-1) on cardiac function using an in vivo model of chronic catecholamine-induced cardiomyopathy were investigated by Roof et al.6 in a rat model. They find the IGF-1 treatment attenuates diastolic and systolic dysfunction that is typically induced by catecholamines when given chronically over weeks. The data suggest that the cardioprotective p110α signalling and activated Akt are involved in the mechanisms behind these observations. The group suggests that their data support the potential use of IGF-1 therapy for clinical applications for cardiomyopathies.6 Central neuronal and neurohumoral and kidney signalling mechanisms7-9 are clearly involved in blood pressure regulation. New evidence about the role of the brain Gαi2 proteins was established in a recent work by Carmichael et al.10 in a rat model using the acute peripheral sodium challenge. They use targeted oligodeoxynucleotide (ODN) to downregulate brain Gαi2 protein expression in the brain. They conclude that Gαi2 protein signal transduction is a novel central mechanism acting to differentially influence paraventricular nucleus parvocellular neuronal activation, sympathetic outflow and arterial pressure in response to acute intravenous hypertonic saline. The anatomic structure nucleus of the solitary tract (NTS) in the brain is thought to be a pivotal region for regulating the set point of arterial pressure. Expression profiling by means of PCR array (targeted for neurotrophins and their receptors) in the nucleus of the solitary tract was used to study the difference between spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats.11 The authors find that a number of genes are differentially expressed genes, among them Gfrα-3, corticotropin-releasing hormone-binding protein (Crhbp), interleukin-10 receptor alpha (Il-10ra) and a downregulation of hypocretin (Hcrt) in SHR. To give the study a kind of cause and effect relation, the authors did a microinjection in the NTS of hypocretin-1 that in turn decreased blood pressure in adult SHRs. The authors conclude that altered neurotrophic factors may affect the normal development and function of neuronal circuitry that regulates cardiovascular autonomic activity with the manifestations of neurogenic hypertension in the hypertensive rat model.11 The role of sex in angiotensin-dependent hypertension in rats was investigated by the group of Dai et al.12 by focusing on endoplasmic reticulum stress in the brain subfornical organ. The authors investigated male, intact and ovariectomized female rats that were subjected to a 2-week infusion of angiotensin (ANG II) or saline. As expected, the ANG II increased blood pressure in males and females as compared to the saline groups; however, the intact none-ovariectomized females showed smaller increase in BP. The biomarkers for ER stress in the brain subfornical organ in both males and females were elevated in the ANG II groups; however, elevations in these parameters were less in intact females as compared to males and ovariectomized females. The authors conclude that oestrogen protects females against ANG II-induced brain ER stress.12 The role of H2O2 with respect to ANG II contractions of afferent arterioles in mice after renal ischaemia-reperfusion injury was investigated by Huang et al.13 The authors conclude from their findings that the reduced catalase activity leads to a H2O2 accumulation after renal ischaemia-reperfusion injury, and this in turn buffers the ANG II response of the arterioles which might be act as a type of renal protective mechanism.13 The effect on blood pressure of ACE-inhibiting peptides derived from food proteins was investigated in a SHR rat model by Martin et al.14 The group finds that isoleucine-tryptophan blunts tissue ACE activity, reduces matrix metalloproteinase-2 activity and improves coronary flow reserve. These fascinating findings may suggest that whey protein hydrolysate may serve as innovative food additives in the fight against arterial blood pressure.14 Typical animal models in the study of blood pressure include mice, rats and to a lesser extend dogs. The investigation of giraffes is not typical; however very interesting, since due to the exceptional geometry of the animal we find unique pressure conditions and alterations, for example for the brain, when the giraffe drinks water. The mean arterial blood pressure is twice that of other mammals.15 The authors analysed possible evolutionary adaption in kidney physiology in response to this high value of mean arterial pressure as compared with other mammals. They have found that in giraffes the glomerular filtration rate, effective renal plasma flow and renal artery resistive index are much lower than expected based on body mass of the giraffes. Renal interstitial hydrostatic pressure is more than 10-fold of other mammals which in turn reduces the effective filtration pressure. This high interstitial pressure is supported by a strong renal capsule. The authors regard these findings relevant for the adaptations to the high mean arterial blood pressure in the tallest mammal on earth. In a human study, Gliemann et al.16 investigate whether essential hypertension is associated with altered capillary muscle morphology and density and to what extent exercise training can normalize these parameters. Among differences in expression of selected proteins in hypertensive subjects, the authors find that essential hypertension is associated with decreased lumen area and a tendency for increased basement membrane thickening in capillaries of skeletal muscle. After training, angiogenesis was evident by increased capillary-to-fibre ratio in the hypertensive subjects. The authors suggest that exercise training may improve gas exchange conditions in hypertensive subjects by structural changes of the capillaries.16 One big problem in hypertension research is the measurement of the blood pressure. The problem is related to the nature of the pressure itself, it may change rapidly over time; however, the actual measurement is often only a tiny snapshot of the whole picture. For clinical use, standardized procedures (e.g. relating to ambient conditions, seating position, refraining from caffeine intake and smoking) are recommended to assess the patients’ blood pressure; however, the snapshot problem still remains. Perhaps recent advances in material science17 will possibly add new medical devices in the future for more direct and continuous measurements of the signal that so many researchers are interested in. There is no conflict of interest to declare.