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In the current issue of I Acta Physiologica i , two papers are published investigating the development of arterial hypertension under conditions of pathological loss of free water in two disease models. Aestivation motifs explain hypertension and muscle mass loss in mice with psoriatic skin barrier defect. The contribution of a tentative aestivation versus natriuresis component to CKD-induced hypertension might therefore increase with higher ratio of salt to water intake and minimize for isotonic intake. Aestivation motifs explain hypertension and muscle mass loss in mice with psoriatic skin barrier defect. [Extracted from the article]

Physiologically, macro- and microcirculation differ markedly as macrocirculation deals with pulsatile pressure and flow and microcirculation with steady pressure and flow. Various such haemodynamic aspects correspond to a large heterogeneity in the structure and function of the vascular tree. In the past, diseases such as hypertension and diabetes mellitus were classified on the basis of the structure and function of small and large arteries. The purpose of this paper is to review the cross-talk between the micro- and macrocirculation. We shall discuss this cross-talk from the perspective of the development, physiology and pathology of the entire arterial tree. [ABSTRACT FROM AUTHOR]

Arterial hypertension is a serious medical condition that significantly increases the risks of heart, brain, kidney, and other diseases affecting 1.28 billion adults worldwide. The authors employed an animal model with wild-type (Floxed) and CD-specific deletion of renin (CD renin KO) mice. In animals, immunofluorescence analysis of renal sections from mice after 5 days of acute pyelonephritis revealed apical plasma membrane targeting of AQP2 and pS256-AQP2 in inner medullary collecting ducts. CD renin KO mice had blunted HK-induced intrarenal renin response and developed impaired kaliuresis and elevated plasma potassium level. [Extracted from the article]

The article discusses the report "Niere und Kreislauf," by R. Tigerstedt and P. G. Bergman. The authors in this study had injected extracts from rabbit kidneys and found that cortical, but not medulary injections, caused prolonged blood pressure elevations. The study has been remarkable in many respects and sustained surge of enthusiasm, particularly in hypertension research.

Aim: Our previous studies have demonstrated the importance of dietary factors in the determination of hypertension in Dahl salt‐sensitive (SS) rats. Since the gut microbiota has been implicated in chronic diseases like hypertension, we hypothesized that dietary alterations shift the microbiota to mediate the development of salt‐sensitive hypertension and renal disease. Methods: This study utilized SS rats from the Medical College of Wisconsin (SS/MCW) maintained on a purified, casein‐based diet (0.4% NaCl AIN‐76A, Dyets) and from Charles River Laboratories (SS/CRL) fed a whole grain diet (0.75% NaCl 5L79, LabDiet). Faecal 16S rDNA sequencing was used to phenotype the gut microbiota. Directly examining the contribution of the gut microbiota, SS/CRL rats were administered faecal microbiota transfer (FMT) experiments with either SS/MCW stool or vehicle (Vehl) in conjunction with the HS AIN‐76A diet. Results: SS/MCW rats exhibit renal damage and inflammation when fed high salt (HS, 4.0% NaCl AIN‐76A), which is significantly attenuated in SS/CRL. Gut microbiota phenotyping revealed distinct profiles that correlate with disease severity. SS/MCW FMT worsened the SS/CRL response to HS, evidenced by increased albuminuria (67.4 ± 6.9 vs 113.7 ± 25.0 mg/day, Vehl vs FMT, P =.007), systolic arterial pressure (158.6 ± 5.8 vs 177.8 ± 8.9 mmHg, Vehl vs FMT, P =.09) and renal T‐cell infiltration (1.9‐fold). Amplicon sequence variant (ASV)‐based analysis of faecal 16S rDNA sequencing data revealed taxa that significantly shifted with FMT: Erysipelotrichaceae_2, Parabacteroides gordonii, Streptococcus alactolyticus, Bacteroidales_1, Desulfovibrionaceae_2, Ruminococcus albus. Conclusions: These data demonstrate that dietary modulation of the gut microbiota directly contributes to the development of Dahl SS hypertension and renal injury. [ABSTRACT FROM AUTHOR]

The molecular mechanisms underlying chronic kidney disease (CKD) are poorly understood and treatment options are limited, a situation underpinning the need for elucidating the causative molecular mechanisms and for identifying innovative treatment options. It is emerging that cyclic 3′,5′‐adenosine monophosphate (cAMP) signalling occurs in defined cellular compartments within nanometre dimensions in processes whose dysregulation is associated with CKD. cAMP compartmentalization is tightly controlled by a specific set of proteins, including A‐kinase anchoring proteins (AKAPs) and phosphodiesterases (PDEs). AKAPs such as AKAP18, AKAP220, AKAP‐Lbc and STUB1, and PDE4 coordinate arginine‐vasopressin (AVP)‐induced water reabsorption by collecting duct principal cells. However, hyperactivation of the AVP system is associated with kidney damage and CKD. Podocyte injury involves aberrant AKAP signalling. cAMP signalling in immune cells can be local and slow the progression of inflammatory processes typical for CKD. A major risk factor of CKD is hypertension. cAMP directs the release of the blood pressure regulator, renin, from juxtaglomerular cells, and plays a role in Na+ reabsorption through ENaC, NKCC2 and NCC in the kidney. Mutations in the cAMP hydrolysing PDE3A that cause lowering of cAMP lead to hypertension. Another major risk factor of CKD is diabetes mellitus. AKAP18 and AKAP150 and several PDEs are involved in insulin release. Despite the increasing amount of data, an understanding of functions of compartmentalized cAMP signalling with relevance for CKD is fragmentary. Uncovering functions will improve the understanding of physiological processes and identification of disease‐relevant aberrations may guide towards new therapeutic concepts for the treatment of CKD. [ABSTRACT FROM AUTHOR]

A brief summary of the paper "The muscle–collagen ratio in left ventricular hypertrophy and aorta remodelling in hypertension," which appears in its full version in the current issue, is presented.

Unfortunately, he was not sufficiently observant to get the arterial and venous blood colour differences down correctly gl The fact that elevated blood pressure is lethal is known to us since the 19th century as the result of bedside and "dead-house" observations, as Pickering observed.[1] He commented that high blood pressure can occur in ways. In his discussion, Frank distinguishes between hypertension forms related to underlying renal diseases and hypertension without an obvious cause (similar to Mahomed's conjectures). For Pickering, two questions emerged.[1] What is the mechanism by which blood pressure increases (in all forms of hypertension)? Pickering was well aware of the kidney's putative role in blood pressure regulation and gives Goldblatt full credit.[6] Oddly, Pickering does not appear to ascribe to the idea that pressure natriuresis is the most important of all long-term regulators of arterial pressure. [Extracted from the article]

Abstract: Endothelium‐dependent responses were first demonstrated 40 years ago in the aorta. Since then, extensive research has been conducted in vitro using conductance vessels and materials derived from them. However, the microcirculation controls blood flow to vital organs and has been the focus of in vivo studies of endothelium‐dependent dilation beginning immediately after the first in vitro report. Initial in vivo studies employed a light/dye technique for selectively damaging the endothelium to unequivocally prove, in vivo, the existence of endothelium‐dependent dilation and in the microvasculature. Endothelium‐dependent constriction was similarly proven. Endothelium‐dependent agonists include acetylcholine (ACh), bradykinin, arachidonic acid, calcium ionophore A‐23187, calcitonin gene‐related peptide (CGRP), serotonin, histamine and endothelin‐1. Normal and disease states have been studied. Endothelial nitric oxide synthase, cyclooxygenase and cytochrome P450 have been shown to generate the mediators of the responses. Some of the key enzyme systems generate reactive oxygen species (ROS) like superoxide which may prevent EDR. However, one ROS, namely H2O2, is one of a number of hyperpolarizing factors that cause dilation initiated by endothelium. Depending upon microvascular bed, a single agonist may use different pathways to elicit an endothelium‐dependent response. Interpretation of studies using inhibitors of eNOS is complicated by the fact that these inhibitors may also inhibit ATP‐sensitive potassium channels. Other in vivo observations of brain arterioles failed to establish nitric oxide as the mediator of responses elicited by CGRP or by ACh and suggest that a nitrosothiol may be a better fit for the latter. [ABSTRACT FROM AUTHOR]

Abstract: The role of salt in the pathogenesis of arterial hypertension is not well understood. According to the current understanding, the central mechanism for blood pressure (BP) regulation relies on classical studies linking BP and Na+ balance, placing the kidney at the very centre of long‐term BP regulation. To maintain BP homeostasis, the effective circulating fluid volume and thereby body Na+ content has to be maintained within very narrow limits. From recent work in humans and rats, the notion has emerged that Na+ could be stored somewhere in the body without commensurate water retention to buffer free extracellular Na+ and that previously unidentified extrarenal, tissue‐specific regulatory mechanisms are operative regulating the release and storage of Na+ from a kidney‐independent reservoir. Moreover, immune cells from the mononuclear phagocyte system not only function as local on‐site sensors of interstitial electrolyte concentration, but also, together with lymphatics, act as systemic regulators of body fluid volume and BP. These studies have established new and unexpected targets in studies of BP control and thus the pathophysiology of hypertension: the interstitium/extracellular matrix of the skin, its inherent interstitial fluid and the lymphatic vasculature forming a vessel network in the interstitium. Aspects of the interstitium in relation to Na+ balance and hypertension are the focus of this review. Taken together, observations of salt storage in the skin to buffer free extracellular Na+ and macrophage modulation of the extracellular matrix and lymphatics suggest that electrolyte homeostasis in the body cannot be achieved by renal excretion alone, but also relies on extrarenal regulatory mechanisms. [ABSTRACT FROM AUTHOR]

The mineralocorticoid aldosterone is a major factor controlling the salt and water balance and thereby also the arterial blood pressure. Accordingly, primary aldosteronism ( PA) characterized by an inappropriately high aldosterone secretion is the most common form of secondary hypertension. The physiological stimulation of aldosterone synthesis in adrenocortical glomerulosa cells by angiotensin II and an increased plasma K+ concentration depends on a membrane depolarization and an increase in the cytosolic Ca2+ activity. Recurrent gain-of-function mutations of ion channels and transporters have been identified in a majority of cases of aldosterone-producing adenomas and in familial forms of PA. In this review, the physiological role of these genes in the regulation of aldosterone synthesis and the altered function of the mutant proteins as well are described. The specific changes of the membrane potential and the cellular ion homoeostasis in adrenal cells expressing the different mutants are compared, and their impact on autonomous aldosterone production and proliferation is discussed. [ABSTRACT FROM AUTHOR]

Pregnancy is a critical time for long-term blood pressure regulation in both mother and child. Pregnancies complicated by placental insufficiency, resulting in pre-eclampsia and intrauterine growth restriction, are associated with a threefold increased risk of the mother to develop hypertension later in life. In addition, these complications create an adverse intrauterine environment, which programmes the foetus and the second generation to develop hypertension in adult life. Female offspring born to a pregnancy complicated by placental insufficiency are at risk for pregnancy complications during their own pregnancies as well, resulting in a vicious circle with programmed risk for hypertension passing from generation to generation. Here, we review the epidemiology and mechanisms leading to the altered programming of blood pressure trajectories after pregnancies complicated by placental insufficiency. Although the underlying mechanisms leading to hypertension remain the subject of investigation, several abnormalities in angiotensin sensitivity, sodium handling, sympathetic activity, endothelial function and metabolic pathways are found in the mother after exposure to placental insufficiency. In the child, epigenetic modifications and disrupted organ development play a crucial role in programming of hypertension. We emphasize that pregnancy can be viewed as a window of opportunity to improve long-term cardiovascular health of both mother and child, and outline potential gains expected of improved preconceptional, perinatal and post-natal care to reduce the development of hypertension and the burden of cardiovascular disease later in life. Perinatal therapies aimed at reprogramming hypertension are a promising strategy to break the vicious circle of intergenerational programming of hypertension. [ABSTRACT FROM AUTHOR]

Chronic kidney disease ( CKD) carries a large cardiovascular burden in part due to hypertension and neurohumoral dysfunction - manifesting as sympathetic overactivity, baroreflex dysfunction and chronically elevated circulating vasopressin. Alterations within the central nervous system ( CNS) are necessary for the expression of neurohumoral dysfunction in CKD; however, the underlying mechanisms are poorly defined. Uraemic toxins are a diverse group of compounds that accumulate as a direct result of renal disease and drive dysfunction in multiple organs, including the brain. Intensive haemodialysis improves both sympathetic overactivity and cardiac baroreflex sensitivity in renal failure patients, indicating that uraemic toxins participate in the maintenance of autonomic dysfunction in CKD. In rodents exposed to uraemia, immediate early gene expression analysis suggests upregulated activity of not only pre-sympathetic but also vasopressin-secretory nuclei. We outline several potential mechanisms by which uraemia might drive neurohumoral dysfunction in CKD. These include superoxide-dependent effects on neural activity, depletion of nitric oxide and induction of low-grade systemic inflammation. Recent evidence has highlighted superoxide production as an intermediate for the depolarizing effect of some uraemic toxins on neuronal cells. We provide preliminary data indicating augmented superoxide production within the hypothalamic paraventricular nucleus in the Lewis polycystic kidney rat, which might be important for mediating the neurohumoral dysfunction exhibited in this CKD model. We speculate that the uraemic state might serve to sensitize the central actions of other sympathoexcitatory factors, including renal afferent nerve inputs to the CNS and angiotensin II, by way of recruiting convergent superoxide-dependent and pro-inflammatory pathways. [ABSTRACT FROM AUTHOR]

Aim High dietary K+ intake is associated with protection against hypertension. In mammals, acute K+ intake induces natriuresis and kaliuresis, associated with a marked dephosphorylation of the renal Na+/Cl− cotransporter ( NCC). It has been suggested that reduced activity of NCC increases the driving force for more distal tubular epithelial Na+ channel ( ENaC)-dependent K+ secretion. This study investigated the ENaC dependence of urinary K+ and Na+ excretion following acute K+ loading. Methods Mice were fed low (0.03%), control (0.2%) or high (2%) Na+ diets for 25 days to preserve or promote Na+ loss and thus ENaC activity. Once a week, the mice received either K+-containing gavage or a control gavage. Following the gavage treatment, the mice were placed in metabolic cages and urine was collected in real time. ENaC dependence of kaliuresis was assessed by benzamil injections prior to gavage. Results We confirmed that dietary Na+ content is inversely related to plasma aldosterone, NCC phosphorylation and ENaC cleavage products. The novel findings were as follows: (i) acute K+ feeding caused NCC dephosphorylation in all dietary groups; (ii) under all dietary conditions, K+ loading induced natriuresis; (iii) high Na+ diet markedly reduced the K+ excretion following K+ gavage; (iv) benzamil injection prior to K+ loading increased natriuresis, decreased kaliuresis and eliminated the differences between the dietary groups. Conclusion These data indicate that acute K+-induced kaliuresis is ENaC dependent. Maximal K+ excretion rates are attenuated when ENaC is physiologically down-regulated or pharmacologically blocked. NCC is dephosphorylated following acute K+ loading under all dietary Na+ regimens. This leads to natriuresis, even in severely Na+-restricted animals. [ABSTRACT FROM AUTHOR]

Background Adipose afferent reflex ( AAR) contributes to sympathetic activation and hypertension. Paraventricular nucleus ( PVN) plays an important role in AAR and sympathetic outflow. The aim of the present study was to determine whether PVN mediates AAR response to insulin in a rat model of insulin resistance ( IR). Methods Male Sprague-Dawley rats were randomly divided into Control and IR groups. Insulin resistance was induced by supplementing fructose (125 g L−1, 12 weeks) in the drinking water. Renal sympathetic nerve activity ( RSNA) and mean arterial pressure ( MAP) were recorded in anesthetized rats. AAR was evaluated by the RSNA and MAP responses to injection of capsaicin into four sites of right inguinal white adipose tissue. Results Rats in IR group showed a rise in plasma noradrenaline ( NE), glucose, insulin and triglyceride levels, left ventricular weight, systolic blood pressure, homeostasis model assessment of insulin resistance ( HOMA- IR) and PVN glucose and insulin levels, melanocortin 4 type receptors ( MC4Rs) protein expression, but not MC3Rs and insulin receptors. Compared with Control group, AAR in IR group was significantly enhanced, which contributed to the elevation of NE level; and insulin microinjection into the PVN or the third ventricle significantly strengthened AAR, which was attenuated by pre-treatment with MC4Rs antagonist HS024 and anti-insulin affibody, respectively, but not insulin receptors antagonist S961. Conclusion The enhanced AAR participates in sympathetic activation in IR, which can be strengthened by PVN insulin. PVN MC4Rs mediate the AAR response to insulin in IR, but not MC3Rs and insulin receptors. [ABSTRACT FROM AUTHOR]

Aim The Na+/H+ exchanger NHE3 activity decreases in the proximal tubule of spontaneously hypertensive rats ( SHRs) as blood pressure increases, and this reduction is correlated with higher NHE3 phosphorylation levels at the PKA consensus site serine 552. This study tested the hypothesis that this lowered NHE3 activity is associated with an increase in PKA activity and expression, and/or a decrease in protein phosphatase-1 ( PP1) activity and expression. Methods Proximal tubule NHE3 activity was measured as the rate of bicarbonate reabsorption by stationary microperfusion. NHE3 phosphorylation and protein expression were determined by immunoblotting. PKA and PP1 activities were determined using specific substrates under optimal enzymatic conditions. Results The PKA activator, 6-MB- cAMP, increased the phosphorylation levels of NHE3 at serine 552 in the renal cortex; this increase happens to a much greater extent in young pre-hypertensive SHRs (Y-SHRs) compared to adult SHRs with established hypertension (A-SHRs). Likewise, the inhibitory effect of 6-MB- cAMP on NHE3 transport activity was much more pronounced in the proximal tubules of Y-SHRs than in those of A-SHRs. Renal cortical activity of PKA was not significantly different between Y-SHRs and A-SHRs. On the other hand, Y-SHRs exhibited higher protein phosphatase 1 (PP1) activity, and their expression of the PP1 catalytic subunit PP1 α in the renal cortex was also higher than in A-SHRs. Conclusion Collectively, these results support the idea that the lower NHE3 transport activity and higher phosphorylation occurring after the development of hypertension in SHRs are due, at least in part, to reduced PP1-mediated dephosphorylation of NHE3 at serine 552. [ABSTRACT FROM AUTHOR]

The article offers information on the pathophysiology of primary hypertension and secondary hypertension. Topics discussed include renal artery stenosis, pharmacological and non-pharmacological approaches in the therapy of hypertension, and role of kidney in primary hypertension. Also mentioned are the relation between low nephron number and hypertension, and arterial blood pressure control, and hormonal control mechanism.

Mother-child cohort studies have established that both pre-pregnancy body mass index ( BMI) and gestational weight gain are independently associated with cardio-metabolic risk factors in young adult offspring, including systolic and diastolic blood pressure. Animal models in sheep and non-human primates provide further evidence for the influence of maternal obesity on offspring cardiovascular function, whilst recent studies in rodents suggest that perinatal exposure to the metabolic milieu of maternal obesity may permanently change the central regulatory pathways involved in blood pressure regulation. Leptin plays an important role in the central control of appetite, is also involved in activation of efferent sympathetic pathways to both thermogenic and non-thermogenic tissues, such as the kidney, and is therefore implicated in obesity-related hypertension. Leptin is also thought to have a neurotrophic role in the development of the hypothalamus, and altered neonatal leptin profiles secondary to maternal obesity are associated with permanently altered hypothalamic structure and function. In rodent studies, maternal obesity confers persistent sympathoexcitatory hyper-responsiveness and hypertension acquired in the early stages of development. Experimental neonatal hyperleptinaemia in naive rat pups provides further evidence of heightened sympathetic tone and proof of principle that hyperleptinaemia during a critical window of hypothalamic development may directly lead to adulthood hypertension. Insight from these animal models raises the possibility that early-life exposure to leptin in humans may lead to early onset essential hypertension. Ongoing mother-child cohort and intervention studies in obese pregnant women provide a unique opportunity to address associations between maternal obesity and offspring cardiovascular function. The goal of the review is to highlight the potential importance of leptin in the developmental programming of hypertension in obese pregnancy. [ABSTRACT FROM AUTHOR]

The article focuses on the sex differences in cardiovascular diseases including heart disease, hypertension, and arrhythmias. It mentions that men are more prone to cardiovascular disease as compared to women in their premenopausal stage, according to several clinical experiments. It states that obesity is associated with cardiovascular diseases in which sex steroids like oestrogen has a significant role.

Aim To elucidate the abnormality of vagal control in spontaneously hypertensive rats ( SHR) by measuring left ventricular myocardial interstitial acetylcholine ( ACh) release in response to α2-adrenergic stimulation as an index of in vivo vagal nerve activity. Methods A cardiac microdialysis technique was applied to the rat left ventricle in vivo, and the effect of α2-adrenergic stimulation by medetomidine or electrical vagal nerve stimulation on myocardial interstitial ACh levels was examined in normotensive Wistar-Kyoto rats ( WKY) and SHR under anaesthetized conditions. Results Intravenous medetomidine (0.1 mg kg−1) significantly increased the ACh levels in WKY (from 2.4 ± 0.6 to 4.2 ± 1.3 nmol L−1, P < 0.05, n = 7) but not in SHR (from 2.5 ± 0.7 to 2.7 ± 0.7 nmol L−1, n = 7). In contrast, electrical vagal nerve stimulation increased the ACh levels in both WKY (from 1.0 ± 0.4 to 2.9 ± 0.9 nmol L−1, P < 0.001, n = 6) and SHR (from 0.9 ± 0.2 to 2.2 ± 0.4 nmol L−1, P < 0.001, n = 6). Intravenous administration of medetomidine (0.1 mg kg−1) did not affect the vagal nerve stimulation-induced ACh release in either WKY or SHR. Conclusion Medetomidine-induced central vagal activation was impaired in SHR, whereas peripheral vagal control of ACh release was preserved. In addition to abnormal sympathetic control, vagal control by the central nervous system may be impaired in SHR. [ABSTRACT FROM AUTHOR]

Aim: Cardiac autonomic modulation and baroreflex sensitivity (BRS) are altered in individuals with hypertension. Aerobic exercise (AE) training has been shown to improve both measures, yet little is known about the effects of resistance exercise (RE). The purpose of this study was to examine the heart rate variability (HRV) and BRS following 4 weeks of resistance or aerobic training in a population with borderline high blood pressure (BP). Methods: Twenty-nine mild hypertensives were recruited and randomly assigned to 4 weeks of RE or AE training. Before and after training, resting measures of HRV frequencies and BRS were obtained. Results: There was a significant decrease in resting systolic BP for both exercise training modes (RE 136 ± 3.0 pre- to 132 ± 3.4 post-training vs. AE 142 ± 4.0 pre- to 137 ± 3.6 mmHg post-training, P = 0.019). Diastolic BP decreased significantly following both exercise training modes (RE 78 ± 1.31 pre to 74 ± 1.1 post vs. AE 80 ± 1.7 pre to 77 ± 1.6 mmHg post, P = 0.002). A significant time by training mode interaction for low frequency : high frequency (HF) ratio ( P = 0.017) with AE decreasing the ratio (275.21 ± 67.28 to 161.26 ± 61.49) and RE increasing this ratio (143.73 ± 65.00 to 227.83 ± 59.41). Natural log-transformed (ln) HRV values showed a time-by-training mode interaction for ln HF ( P = 0.05) as ln HF increased (4.7 ± 0.38 to 5.4 ± 0.35 ms2) following AE and decreased (5.98 ± 0.37 to 5.76 ± 0.42 ms2) following RE. BRS increased following aerobic training and decreased after resistance training (6.74 ± 1.2 to 7.94 ± 1.3 and 10.44 ± 1.2 to 9.1 ± 1.2 ms mmHg−1 respectively, P = 0.021). Conclusions: Aerobic exercise improved the autonomic nervous system (increasing vagal tone, reducing sympathovagal balance while increasing BRS) while RE showed no improvements in cardiac autonomic tone and decreased BRS. [ABSTRACT FROM AUTHOR]

Caveolae are omega-shaped membrane invaginations present in essentially all cell types in the cardiovascular system, and numerous functions have been ascribed to these structures. Caveolae formation depends on caveolins, cholesterol and polymerase I and transcript release factor-Cavin (PTRF-Cavin). The current review summarizes and critically discusses the cardiovascular phenotypes reported in caveolin-1-deficient mice. Major changes in the structure and function of heart, lung and blood vessels have been documented, suggesting that caveolae play a critical role at the interface between blood and surrounding tissue. According to an emerging paradigm, many of these changes are secondary to uncoupling of endothelial nitric oxide synthase. Thus, nitric oxide synthase not only synthesizes more nitric oxide in the absence of caveolin-1, but also more superoxide with potential pathogenic consequences. It is further argued that the vasodilating drive from increased nitric oxide production in caveolin-1-deficient mice is balanced by changes in the vascular media that favour increased dynamic resistance regulation. Harnessing the therapeutic opportunities buried in caveolae, while challenging, could expand the arsenal of treatment options in cancer, lung disease and atherosclerosis. [ABSTRACT FROM AUTHOR]

Aim: Hypertension is a common disease in the industrialized world and approximately 5% of all cases are secondary to kidney malfunction. We have recently shown that hydronephrosis due to partial unilateral ureteral obstruction (PUUO) causes salt-sensitive hypertension in rats. The mechanisms are still unclear, but appear to be intrarenal and primarily located to the diseased kidney. In the present study, we have developed a model for PUUO to study if hydronephrotic mice develop salt-sensitive hypertension. Methods: PUUO was created in 3-week-old mice (C57bl/6J). Blood pressure and heart rate were measured telemetrically in adult animals on normal and high salt diets. Metabolism cages were used to study the renal excretion of electrolytes and water. Plasma samples for renin analysis were collected and renal histological changes were evaluated. Results: All hydronephrotic animals developed salt-sensitive hypertension that correlated to the degree of hydronephrosis. In hydronephrotic animals, blood pressure increased from 114 ± 1 mmHg on normal salt diet to 120 ± 2 mmHg on high salt diet, compared with 103 ± 1 to 104 ± 1 in controls. Hydronephrotic animals showed increased diuresis and reduced ability to regulate electrolyte concentration. No differences in plasma renin concentration were found between the groups. The parenchymal weight and glomerular area of contralateral kidneys were significantly increased in the hydronephrotic animals. Histopathology of the hydronephrotic kidneys displayed areas with fibrosis, inflammation and glomerular changes. Conclusion: This study provides a model for PUUO in mice and demonstrates the presence of salt-sensitive hypertension and an impaired renal concentrating ability in mice which has not been described before. [ABSTRACT FROM AUTHOR]

Aim: The incidence of hydronephrosis due to ureteropelvic junction obstruction is approx. 0.5%. During the last decade, the management of non-symptomatic hydronephrosis has become much more conservative, but the long-term physiological consequences of this policy are not clear. Previously, we have shown that animals with chronic partial unilateral ureteral obstruction develop salt-sensitive hypertension. In this study, the effects of ipsilateral and contralateral nephrectomy and ureterovesicostomy on blood pressure were studied in hydronephrotic animals. Methods: Partial unilateral ureteral obstruction was created in 3-week-old male Sprague–Dawley rats and blood pressure was measured telemetrically 4–6 weeks later during a normal and high salt diet before and after uninephrectomy or ureterovesicostomy. Plasma samples for renin assay were collected during both diets before and after ipsilateral nephrectomy. Results: All hydronephrotic animals developed salt-sensitive hypertension, of different degrees. Before nephrectomy the plasma renin concentration was significantly higher in the hydronephrotic animals than in controls (160 ± 15 μGU mL−1 vs. 96 ± 12 μGU mL−1, respectively), but after the ipsilateral nephrectomy no differences were found between the groups. In the hydronephrotic animals both ipsilateral nephrectomy and ureterovesicostomy reduced the blood pressure and salt-sensitivity but the former still differed significantly from the controls. In contralaterally, nephrectomized hydronephrotic animals the salt-sensitive hypertension became more pronounced. Conclusion: Hydronephrosis in rats causes salt-sensitive hypertension that can be markedly reduced by removing the hydronephrotic kidney or relieving the obstruction by ureterovesicostomy. The mechanisms appear to be intrarenal and primarily located in the diseased kidney, but a secondary mechanism is also present. [ABSTRACT FROM AUTHOR]

Aim: Whereas prostaglandin E2 has been characterized as the principal vasodepressor lipid, medullipin remains a hypothetical vasodepressor principle of the renal medulla. Representing the first step towards the isolation of medullipin as a pure compound, the aim of the present study was to determine whether or not the known vasodilator and antihypertensive action of prostaglandins play a role in the antihypertensive activity of renal medulla. Methods: A chloroform extract of porcine kidney medulla was fractionated by gradient vacuum liquid chromatography (VLC) and analysed by capillary GC-MS for the presence of prostaglandins (detection limit: 2.2 ppm). The biological activity was determined in spontaneously hypertensive Wistar rats. The particle size of injectable colloids prepared from extract and fractions was controlled by photon correlation spectroscopy. Results: The extract caused a pronounced blood pressure decline (29.6 ± 6.3/24.9± 5.5 mmHg; P = 0.0078; 10 mg kg−1 body weight; particle size of 143 ± 18 nm; n = 7) lasting for more than 1 h. The heart rate remained stable, showing only a slightly decrease. All fractions were shown to be devoid of vasodilator prostanoid substances. The VLC procedure allowed the successful separation of endogenous emulsifiers from the active principle. An extract from the renal cortex did not exhibit a similar vasodepressor effect. Conclusion: Prostaglandins are excluded as the blood pressure-lowering active principle of a total lipid kidney medulla extract. The vasodepressor principle is contained in the kidney medulla, but not in the cortex. It can be separated from endogenous emulsifying substances, is chromatographically stable, and is amenable to purification and chemical characterization. [ABSTRACT FROM AUTHOR]

The article discusses obesity-related hypertension, particularly on the baroreceptor resetting related to chronic arterial hypertension and the recommended pharmacological strategy to treat the disease. Also cited are the effectiveness of calcineurin phosphatase inhibitor-type immunosuppressant tacrolimus in restoring baroreceptor sensitivity, how the arterial baroreceptors adapt to elevated blood pressure, and the study by S. A. Khan and colleagues on obesity-induced hypertension in rats.

Aim: Disturbances of renal medullary perfusion and metabolism have been implicated in the pathogenesis of kidney disease and hypertension. Furosemide, a loop diuretic, is widely used to prevent renal medullary hypoxia in acute kidney disease by uncoupling sodium metabolism, but its effects on medullary perfusion in humans are unknown. We performed quantitative imaging of both renal perfusion and oxygenation using Magnetic Resonance Imaging (MRI) before and during furosemide. Based on the literature, we hypothesized that furosemide would increase medullary oxygenation, decrease medullary perfusion, but cause minor changes (<10%) in renal artery flow (RAF). Methods: Interleaved measurements of RAF, oxygenation (T2*) and perfusion by arterial spin labelling in the renal cortex and medulla of 9 healthy subjects were acquired before and after an injection of 20 mg furosemide. They were preceded by measurements made during isometric exercise (5 minutes handgrip bouts), which are known to induce changes in renal hemodynamics, that served as a control for the sensitivity of the hemodynamic MRI measurements. Experiments were repeated on a second day to establish that the measurements and the induced changes were reproducible. Results: After furosemide, T2* values in the medulla increased by 53% (P < 0.01) while RAF and perfusion remained constant. After hand‐grip exercise, T2* values in renal medulla increased by 22% ± 9% despite a drop in medullary perfusion of 7.2% ± 4.7% and a decrease in renal arterial flow of 17.5% ± 1.7% (P < 0.05). Mean coefficients of variation between repeated measurements for all parameters were 7%. Conclusion: Furosemide induced the anticipated increase in renal medullary oxygenation, attributable exclusively to a decrease in renal oxygen consumption, since no change of RAF, cortical or medullary perfusion could be demonstrated. All measures and the induced changes were reproducible. [ABSTRACT FROM AUTHOR]

Soluble guanylyl cyclase (sGC) is an effector enzyme of nitric oxide (NO). Recent work has unravelled how levels of this enzyme are controlled, and highlighted a role in vascular disease. We provide a timely summary of available knowledge on transcriptional regulation of sGC, including influences from the NOTCH signalling pathway and genetic variants. It is speculated that hypertension‐induced repression of sGC starts a vicious circle that can be initiated by periods of stress, diet or genetic factors, and a key tenet is that reduction in sGC further raises blood pressure. The idea that dysregulation of sGC contributes to syndromes caused by defective NOTCH signalling is advanced, and we discuss drug repositioning for vascular disease prevention. The advantage of targeting sGC expression rather than activity is also considered. It is argued that transcriptional inputs on sGC arise from interactions with other cells, the extracellular matrix and microRNAs (miRNAs), and concluded that the promise of sGC as a target for prevention of cardiovascular disease has increased in recent time. [ABSTRACT FROM AUTHOR]

The article presents abstracts related to kidney physiology including "Potassium and hypertension" by J. Loffing, "Diverse functions of mineralocorticoids" by F. Lang, and "Plasticity of renal endocrine function" by B. Kurt.

The article provides information on a study that examined the pericyte hypothesis in rats. The researchers tested the process by simultaneous administration of two different antiapoptotic drugs which abolished the effect of losartan on pericyte number. Based on the results, they concluded that transient angiotensin II receptor blocked the late medullary effects in immature hypertensive rats.