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The paper reviews findings in humans regarding interindividual differences in sympathetic nerve activity. Data come predominantly from microneurographic multi- or single fibre recordings of sympathetic nerve activity in healthy subjects. Findings relate to interindividual differences in muscle sympathetic nerve activity (MSNA) during resting conditions and in response to surprising sensory stimuli. At rest there are marked interindividual differences in the number of multiunit MSNA bursts. At the single fibre level the differences are because of more vasoconstrictor fibres being active in subjects with high than in subjects with low number of bursts. There are inverse relationships between (i) sympathetic burst incidence and cardiac output (CO) and (ii) between sympathetic burst incidence and vascular responsiveness to noradrenaline. Both findings contribute to explaining the absence of correlation between resting levels of MSNA and blood pressure. Surprising visual, somatosensory or auditory stimuli of sufficient strength cause a short lasting inhibition of MSNA in approx. 50–60% of healthy subjects. In subjects who display significant inhibition, the stimulus-induced blood pressure increase is smaller than in subjects without inhibition. The underlying mechanism may be related to fear of blood/injury. It is concluded that analysis of interindividual differences in sympathetic activity improves the understanding of central nervous control of the circulation. [ABSTRACT FROM AUTHOR]

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.

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]

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]

Weightlessness in space induces a fluid shift from the dependent to the cephalad parts of the body leading to distension of the cardiac chambers and an accumulation of blood in the veins of the head and neck. Surprisingly, central venous pressure (CVP) during the initial hours of spaceflight decreases compared to being horizontal supine on the ground. The explanation is that the thorax is expanded by weightlessness leading to a decrease in inter‐pleural pressure (IPP), which exceeds the measured decrease in CVP. Thus, transmural CVP (TCVP = CVP − IPP) is increased indicating an augmented cardiac preload. Simultaneously, stroke volume and cardiac output (CO) are increased by 18%‐26% within the initial weeks and more so by 35%‐56% during the subsequent months of flight relative to in the upright posture on the ground. Mean arterial pressure (MAP) is decreased indicating a lower systemic vascular resistance (MAP/CO). It is therefore a surprise that sympathetic nerve activity is not suppressed in space and thus cannot be a mechanism for the systemic vasodilation, which still needs to be explored. Recent observations indicate that the fluid shift during long duration (months) flights is associated with increased retinal thickness that sometimes leads to optical disc oedema. Ocular and cerebral structural changes, increases in left atrial size and decreased flows with thrombi formation in the left internal jugular vein have also been observed. This is of concern for future long duration deep space missions because the health implications are unknown. [ABSTRACT FROM AUTHOR]

Abstract: For at least the last 30 years, it has been discussed whether mean arterial blood pressure (MAP) is independent of body mass or whether it increases in accordance with the vertical height between the heart and the brain. The debate has centred on the most appropriate mathematical models for analysing allometric scaling and phylogenetic relationships; there has been previously little focus on evaluating the validity of underlying physiological data. Currently, the 2 most comprehensive scaling analyses are based on data from 47 species of mammals, based on 114 references. We reviewed all available references to determine under which physiological conditions MAP had been recorded. In 44 (38.6%) of the cited references, MAP was measured in anaesthetized animals. Data from conscious animals were reported in 59 (51.8%) of references; of these, 3 (2.6%) were radiotelemetric studies. In 5 species, data were reported from both anaesthetized and conscious animals, and the mean difference in the MAP between these settings was 20 ± 29 mm Hg. From a literature search, we identified MAP measurements performed by radiotelemetry in 11 of the 47 species included in the meta‐analyses. A Bland‐Altman analysis showed a bias of 1 mm Hg with 95% confidence interval (from −35 to 36 mm Hg); that is, the limits of agreement between radiotelemetric studies and studies in restrained animals were double the supposed difference in the MAP between the mouse and elephant. In conclusion, the existing literature does not provide evidence for either a positive or neutral scaling of arterial pressure to body mass across taxa. [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]

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]

Aim: The study examined the role of the motor cortex in the control of human standing. Methods: Subjects ( n = 15) stood quietly with or without body support. The supported standing condition enabled subjects to stand with a reduced amount of postural sway. Peripheral electrical stimulation, transcranial magnetic stimulation (TMS) or transcranial electrical stimulation (TES) was applied to elicit a soleus (SOL) H-reflex, or motor-evoked potentials (MEPs) in the SOL and the tibialis anterior (TA). Trials were grouped based on the standing condition (i.e. supported vs. normal) as well as sway direction (i.e. forward and backward) while subjects were standing normally. Results: During normal when compared to supported standing, the SOL H-reflex was depressed (−11 ± 4%), while the TMS-evoked MEPs from the SOL and TA were facilitated (35 ± 11% for the SOL, 51 ± 15% for the TA). TES-evoked SOL and TA MEPs were, however, not different between the normal and supported standing conditions. The data based on sway direction indicated that the SOL H-reflex, as well as the SOL TMS- and TES-evoked MEPs were all greater during forward when compared to backward sway. In contrast, the TMS- and TES-evoked MEPs from the TA were smaller when swaying forward as compared to backward. Conclusions: The results indicated the presence of an enhanced cortical excitability because of the need to control for postural sway during normal standing. The increased cortical excitability was, however, unlikely to be involved in an on-going control of postural sway, suggesting that postural sway is controlled at the spinal and/or subcortical levels. [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]

Aims: Cardiac failure and ischaemic heart disease patients receive standard of care cardiac β1-adrenergic blockade medication. Such medication reduces cardiac output and cerebral blood flow. It is unknown whether the β1-adrenergic blockade-induced reduction of cardiac output in the presence of an exercise-induced reduction in cardiac–arterial baroreflex gain affects cerebral blood flow variability. This study evaluated the influence of cardiac output variability on beat-to-beat middle cerebral artery mean blood velocity (MCA Vmean) during exercise with and without cardiac β1-adrenergic blockade. Methods: Eight men (22 ± 1 years; mean ± SE) performed 15 min bouts of moderate (105 ± 11 W) and heavy (162 ± 8 W) intensity cycling before and after cardio-selective β1-adrenergic blockade (0.15 mg kg−1 metoprolol). The relationship between changes in cardiac output or mean arterial pressure (MAP) and MCA Vmean as well as cardiac–arterial baroreflex gain were evaluated using transfer function analysis. Results: Both exercise intensities decreased the low frequency (LF) transfer function gain between cardiac output and MCA Vmean ( P < 0.05) with no significant influence of β1-blockade. In contrast, the LF transfer function gain between MAP and MCA Vmean remained stable also with no significant influence of metoprolol ( P > 0.05). The LF transfer function gain between MAP and HR, an index of cardiac–arterial baroreflex gain, decreased from rest to heavy exercise with and without β1-blockade ( P < 0.05). Conclusion: These findings suggest that the exercise intensity related reduction in cardiac–arterial baroreflex function at its operating point does not influence the dynamic control of MCA Vmean, even when the ability of exercise-induced increase in cardiac output is reduced by cardiac β1-adrenergic blockade. [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 presents the author's insights on the study of Ulf S. von Euler and G. Liljestrand on the reactions of the pulmonary arterial blood pressure. The author says that the rise of the pressure reactions was interpreted by the researchers as caused by changes in the pulmonary vascular resistance. He adds that the assumptions of the researchers about the effects of oxygen (O)2 and carbon dioxide (CO)2 on the pulmonary vessels were confirmed using the circulation pump.

The author argues against the study conducted by researchers Carmichael and colleagues on the role of central guanine nucleotide binding protein (Ga2)-protein mediated signal transduction in the response of Sprague-Dawley rats to acute salt loading. The author states that Ga2 proteins participate in central and peripheral mechanisms of blood pressure control. The author mentions the need of further studies that should focused on alterations of Ga2-dependent symphathionhibitory.