Regulation of blood pressure and salt homeostasis by endothelin

Endothelin (ET) peptides and their receptors are intimately involved in the physiological control of systemic blood pressure and body Na homeostasis, exerting these effects through alterations in a host of circulating and local factors. Hormonal systems affected by ET include natriuretic peptides, aldosterone, catecholamines, and angiotensin. ET also directly regulates cardiac output, central and peripheral nervous system activity, renal Na and water excretion, systemic vascular resistance, and venous capacitance. ET regulation of these systems is often complex, sometimes involving opposing actions depending on which receptor isoform is activated, which cells are affected, and what other prevailing factors exist. A detailed understanding of this system is important; disordered regulation of the ET system is strongly associated with hypertension and dysregulated extracellular fluid volume homeostasis. In addition, ET receptor antagonists are being increasingly used for the treatment of a variety of diseases; while demonstrating benefit, these agents also have adverse effects on fluid retention that may substantially limit their clinical utility. This review provides a detailed analysis of how the ET system is involved in the control of blood pressure and Na homeostasis, focusing primarily on physiological regulation with some discussion of the role of the ET system in hypertension.     

Systemic hemodynamic effects of leukotrienes C4 and D4 in the rat

Although local administration of the sulfidopeptide leukotrienes into cutaneous and coronary vascular beds indicates that these naturally occurring metabolites of arachidonic acid are vasoconstrictors, their systemic administration has produced both pressor and depressor responses. The systemic hemodynamic effects of intravenous leukotriene C4 (LTC4) and leukotriene D4 (LTD4) were assessed in ether-anesthetized rats and compared with the effects produced by equimolar doses (2 X 10(-10) to 4 X 10(-8) mol/kg) of norepinephrine and angiotensin. Mean arterial pressure, right atrial pressure, and cardiac output (electromagnetic flowmetry) were recorded during bolus administrations of these vasoactive compounds. LTC4 and LTD4 had similar hemodynamic effects that were characterized by moderate pressure elevations produced by dose-dependent increases in total peripheral resistance, since cardiac output declined. Although the peak mean arterial pressure levels produced by LTC4 and LTD4 (135 +/- 7 and 129 +/- 5 mmHg, respectively) were less than those by norepinephrine (157 +/- 3 mmHg) and angiotensin (174 +/- 5 mmHg), the peak total peripheral resistance values of LTC4 and LTD4 (2.23 +/- 0.32 and 1.86 +/- 0.17 mmHg X ml-1 X min-1, respectively) were between those of the well-known vasopressors, norepinephrine (1.50 +/- 0.09) and angiotensin (2.72 +/- 0.41). The pressor response to LTC4 and LTD4 was less marked than that to norepinephrine and to angiotensin because of the concomitant reduction in cardiac output. These results indicate that LTC4 and LTD4 are systemic vasoconstrictors with potencies similar to those of norepinephrine and angiotensin.     

Effect of prolonged nonpulsatile left heart bypass on vascular control status

We investigated the vascular control status, including vasoactive hormones, systemic vascular resistance (SVR), and baroreceptor sensitivity, in prolonged nonpulsatile left heart bypass (NLHB). Nine goats underwent pulsatile left heart bypass (PLHB) with a ventricular assist device (VAD). Two weeks postoperatively, the VAD was replaced with a centrifugal pump and NLHB was subsequently conducted for 4 weeks. Thirteen healthy goats were also evaluated to obtain normal control data. The aortic pulse pressure on average was 37 mmHg for controls; 36mmHg at the end of PLHB; and 11, 9, 12, and 12mmHg at the end of the first, second, third, and fourth NLHB weeks, respectively. Plasma norepinephrine (NE), vaso-pressin (VP), renin activity (RA), and endothelin-I (ET) levels were measured for controls and at each point during PLHB and NLHB. The baseline SVR and the minimum SVR values after nitroglycerin injection were determined at each point during PLHB and NLHB. Baroreceptor sensitivity was calculated as the regression slope between R-R intervals and mean aortic pressure for controls and at each point during PLHB and NLHB. The plasma levels of NE, VP, RA, and EN did not change significantly during the entire course of the experiments. The baseline and minimum SVR values after nitroglycerin injection remained unchanged during PLHB and NLHB. Furthermore, the baroreceptor sensitivity did not change significantly during the entire course of the experiments. These results indicate that prolonged NLHB does not affect vascular control status, including the major vasoactive hormone levels, SVR, and baroreceptor sensitivity.     

Magnesium transport in hypertension

Epidemiological, clinical and experimental evidence indicates an inverse association between Mg²⁺ levels (serum and tissue) and blood pressure. Magnesium may influence blood pressure by modulating vascular tone and structure through its effects on numerous biochemical reactions that control vascular contraction/dilation, growth/apoptosis, differentiation and inflammation. Magnesium acts as a calcium channel antagonist, it stimulates production of vasodilator prostacyclins and nitric oxide and it alters vascular responses to vasoactive agonists. Mammalian cells regulate Mg²⁺ concentration through specialized influx and efflux transport systems that have only recently been characterized. Magnesium efflux occurs via Na²⁺-dependent and Na²⁺-independent pathways. Mg²⁺ influx is controlled by recently cloned transporters including Mrs2p, SLC41A1, SLC41A1, ACDP2, MagT1, TRPM6 and TRPM7. Alterations in some of these systems may contribute to hypomagnesemia and intracellular Mg²⁺ deficiency in hypertension. In particular increased Mg²⁺ efflux through altered regulation of the vascular Na⁺/Mg²⁺ exchanger and decreased Mg²⁺ influx due to defective vascular and renal TRPM6/7 expression/activity may be important. This review discusses the role of Mg²⁺ in vascular biology and implications in hypertension and focuses on the putative transport systems that control vascular magnesium homeostasis. Much research is still needed to clarify the exact mechanisms of Mg²⁺ regulation in the cardiovascular system and the implications of aberrant transcellular Mg²⁺ transport in the pathogenesis of cardiovascular disease.     

Local control of pulmonary blood flow and lung structure in reptiles: implications for ventilation perfusion matching

Lung structure of reptiles is very diverse ranging from single chambered lungs with a simple structure to more complex and multi-chambered lungs. Increased structural complexity resulted from the evolution of smaller gas exchange units and larger surface area, which increases the pulmonary diffusive capacity for O(2). However, increased structural complexity probably also increases the possibilities for ventilation-perfusion (V /Q ) heterogeneity, which exerts significant constraints on gas exchange. In most reptiles, the ventricle is anatomically and functionally undivided so blood pressures are equal in the systemic and pulmonary circulations. In these species, blood flow distribution between pulmonary and systemic circulations are primarily determined by pulmonary and systemic vascular resistances. Thus, increased pulmonary resistance lowers pulmonary blood flow through increasing cardiac right-to-left shunt decreasing systemic oxygen levels. It has been proposed that local mechanisms regulating pulmonary blood flow are more pronounced in reptiles with complex lungs as they are more prone to V /Q heterogeneity. However, local control of pulmonary blood flow has also been suggested to primarily exist when hearts are functionally divided because altered pulmonary vascular resistance does not affect cardiac shunt patterns. Data suggest that, while there seems to be a general trend of increased local regulation of pulmonary blood flow in species with structurally complex lungs and divided hearts, it is also possible that other factors, such as breathing pattern, have been important for the evolutionary development of local regulatory mechanisms in the lungs.     

Comparison of the reflex vasomotor responses to separate and combined stimulation of the carotid sinus and aortic arch baroreceptors by pulsatile and non-pulsatile pressures in the dog

1. In the anaesthetized dog the carotid sinuses and aortic arch were isolated from the circulation and separately perfused with blood by a method which enabled the mean pressure, pulse pressure and pulse frequency to be varied independently in each vasosensory area. The systemic circulation was perfused at constant blood flow by means of a pump and the systemic venous blood was oxygenated by an extracorporeal isolated pump-perfused donor lung preparation.2. When the vasosensory areas were perfused at non-pulsatile pressures within the normal physiological range of mean pressures, the reflex reduction in systemic vascular resistance produced by a given rise in mean carotid sinus pressure was significantly greater than that resulting from the same rise of aortic arch pressure.3. On the other hand, when the vasosensory areas were perfused at normal pulsatile pressures and within the normal physiological range of mean pressures, there was no difference in the size of the reflex vascular responses elicited by the same rise in mean pressure in the carotid sinuses and in the aortic arch.4. Whereas the vasomotor responses elicited reflexly by changes in mean carotid sinus pressure are modified by alterations in pulse pressure, those evoked by the aortic arch baroreceptors through changes of mean pressure are only weakly affected by modifications in pulse pressure. Evidence for this was obtained from single stepwise changes of mean pressure in each vasosensory area during pulsatile and non-pulsatile perfusion, and from curves relating the mean pressure in the carotid sinuses or aortic arch and systemic arterial perfusion pressure.5. The vasomotor response elicited by combined stimulation of the carotid sinus and aortic arch baroreceptors was greater than either response resulting from their separate stimulation.6. When the mean perfusion pressures in the two vasosensory areas are changed together, the curve relating mean pressure to systemic arterial pressure during pulsatile perfusion of the areas is considerably flatter than that for non-pulsatile perfusion.7. Increasing the pulse pressure in the carotid sinuses or aortic arch caused a decrease in systemic vascular resistance, the response elicited from the carotid sinuses being the larger.8. Altering the phase angle between the pulse pressure waves in the carotid sinuses and aortic arch had no effect on systemic vascular resistance.9. In both vasosensory areas, increasing the pulse frequency caused a reduction in systemic vascular resistance.     

Increase in systemic vascular resistance during acute mental stress in patients with rheumatoid arthritis with high-grade systemic inflammation

Patients with rheumatoid arthritis are at increased risk for myocardial infarction. It has been hypothesized that mental stress-induced cardiovascular reactions may play a role in the triggering of myocardial infarction. Cardiovascular activity was measured during rest, stress, and recovery in rheumatoid arthritis patients with high systemic inflammation (C-reactive protein >8 mg/l), rheumatoid arthritis patients with low systemic inflammation (C-reactive protein 相似文献   

The interrelation of the "local" and the "general" in inflammation

The relationships between the local and the general in inflammation are analysed basing on the literature and original data. Local chemoattraction is postulated to be an underlying factor initiating primary local cooperation of cells relevant to inflammation. Being essential in this cooperation, macrophage seems to warrant both the local developments and triggering of general mechanisms of regulation which are relevant to control over subsequent secondary cell cooperation. The latter is biologically aimed at localization of the inflammation focus and separation of its pathogenic factors from intact internal medium. General mechanisms of inflammation control are provided by neuroendocrine, immune, vascular, coagulative, fibrinolytic and other systems, and operate through the products of the acute phase, by immune defence factors and rearrangement of nervous regulation of homeostasis in intact organs and tissues. The result of the regulation manifests with sequential presentation of the inflammation stages in time, correlation of local and general responses intensity. Eventually, local inflammation and lesion involve stress and intoxication which are not considered direct attributes of inflammation, nevertheless can influence general regulatory systems concerned with the course of local inflammation. It is concluded that inflammation implies dialectic unity of local and systemic responses of the body outlined to resolve inflammation and restore homeostasis.     

BP regulation VI: elevated sympathetic outflow with human aging: hypertensive or homeostatic?

Though conventional wisdom suggests that a rise in blood pressure is a reality of advancing age, in fact, it appears that progressive elevation in sympathetic activity, not necessarily accompanied by increased blood pressure, is intrinsic to cardiovascular aging in humans. The mechanism behind this elevation would seem to reside in homeostatic cardiovascular regulation; nonetheless, the balance of factors that result in elevated sympathetic outflow with age remains elusive. Age-related increases in sympathetic nervous outflow cannot be fully explained by increases in body mass, body adiposity, or other metabolic factors; interrelations among cardiac output, peripheral resistance, and blood pressure may not reflect a determinative hemodynamic interrelation but rather parallel phenomena; and there is no simple linear relationship between baroreflex control and resting levels of sympathetic activity. In contrast to systemic relationships, available data suggest that elevated sympathetic outflow may derive from the inter-relationship between centrally driven sympathoexcitation and a decline in the ability of sympathetic outflow to effect peripheral vascular responses. This review aims to integrate the current knowledge of mechanisms underlying elevated sympathetic outflow with age. It seeks to synthesize these data in the context of proposing that an age-related decline in the ability of sympathetic outflow to effect regional vascular responses incites a compensatory elevation in resting sympathetic activity to maintain homeostatic balance, presumably to maintain adequate control of blood pressure.     

Absence of reflex vascular responses from the intrapulmonary circulation in anaesthetised dogs

The aim of this investigation was to determine whether reflex cardiovascular responses were obtained to localised distension of the intrapulmonary arterial and venous circulations in a preparation in which the stimuli to other major reflexogenic areas were controlled and the lung was shown to possess reflex activity. Dogs were anaesthetised with -chloralose, artificially ventilated, the chests widely opened and a cardiopulmonary bypass established. The intrapulmonary region of the left lung was isolated and perfused through the left pulmonary artery and drained through cannulae in the left pulmonary veins via a Starling resistance. Intrapulmonary arterial and venous pressures were controlled by the rate of inflow of blood and the pressure applied to the Starling resistance. Pressures to the carotid, aortic and coronary baroreceptors and heart chambers were controlled. Responses of vascular resistance were assessed from changes in perfusion pressures to a vascularly isolated hind limb and to the remainder of the subdiaphragmatic circulation (flows constant). The reactivity of the preparation was demonstrated by observing decreases in vascular resistance to large step changes in carotid sinus pressure (systemic vascular resistance decreased by -40 +/- 5%), chemical stimulation of lung receptors by injection into the pulmonary circulation of veratridine or capsaicin (resistance decreased by -32 +/- 4%) and, in the four dogs tested, increasing pulmonary stroke volume to 450 ml (resistance decreased by -24 +/- 6%). However, despite this evidence that the lung was innervated, increases in intrapulmonary arterial pressure from 14 +/- 1 to 43 +/- 3 mmHg or in intrapulmonary venous pressure from 5 +/- 2 to 34 +/- 2 mmHg or both did not result in any consistent changes in systemic or limb vascular resistances. In two animals tested, however, there were marked decreases in efferent phrenic nerve activity. These results indicate that increases in pressure confined to the intrapulmonary arterial and venous circulations do not cause consistent reflex vascular responses, even though the preparation was shown to be reflexly active and the lung was shown to be innervated.     

Pathophysiologic characteristics of the reactive toxic stage of acute suppurative peritonitis and ways to enhance the effectiveness of intensive therapy

The oxygen regimen, circulation, and metabolism were studied in 95 patients in the reactive-toxic stage of diffuse purulent peritonitis. The results of cluster analysis made it possible to determine the clinical and pathophysiological features of the phases of the disease. The phase of compensation was characterized by disorders of mass exchange of plasma water which led to increased index of transcapillary exchange and increased excess of lactate. These parameters of tissue metabolism were grouped into one cluster together with the oxygen regimen value and mean arterial pressure. The other cluster was formed of the values of oxygen consumption and the values of oxygen systemic and vascular tissue transport and the hemodynamic parameters. In the phase of decompensation the homeostasis parameters were grouped into another 2 clusters. The first contained the indices of transcapillary exchange of oxygen and water, the other--those of the intensity of blood oxygen transport function and metabolism. Surgical treatment and inclusion of the sympatholytic agent ornid and the beta-adrenergic agonist alupent in the complex of intensive therapy from the stages of preoperative and anesthesiological management brought homeostasis to a level characteristic of the phase of compensation, as a result of which fatal outcomes were absolutely excluded.     

Protein kinase G-I deficiency induces pulmonary hypertension through Rho A/Rho kinase activation

Protein kinase G (PKG) plays an important role in the regulation of vascular smooth cell contractility and is a critical mediator of nitric oxide signaling, which regulates cardiovascular homeostasis. PKG-I-knockout (Prkg1(-/-)) mice exhibit impaired nitric oxide/cGMP-dependent vasorelaxation and systemic hypertension. However, it remains unknown whether PKG-I deficiency induces pulmonary hypertension. In this study, we characterized the hypertensive pulmonary phenotypes in Prkg1(-/-) mice and delineated the underlying molecular basis. We observed a significant increase in right ventricular systolic pressure in Prkg1(-/-) mice in the absence of systemic hypertension and left-sided heart dysfunction. In addition, we observed marked muscularization of distal pulmonary vessels in Prkg1(-/-) mice. Microangiography revealed impaired integrity of the pulmonary vasculature in Prkg1(-/-) mice. Mechanistically, PKG-I-mediated phosphorylation of Rho A Ser188 was markedly decreased, and the resultant Rho A activation was significantly increased in Prkg1(-/-) lung tissues, which resulted in Rho kinase activation. The i.t. administration of fasudil, a Rho kinase inhibitor, reversed the hypertensive pulmonary phenotype in Prkg1(-/-) mice. Taken together, these data show that PKG-I deficiency induces pulmonary hypertension through Rho A/Rho kinase activation-mediated vasoconstriction and pulmonary vascular remodeling.     

Haemodynamic and humoral responses to repeated hypotensive haemorrhage in conscious sheep

Haemodynamic and humoral responses to two subsequent hypotensive haemorrhages, separated by 3 hours and each followed by retransfusion, were studied in unanaesthetized sheep. Haemorrhage was induced by removal of blood from a jugular vein at a rate of 0.7 ml kg-1 min-1 until the mean systemic arterial pressure suddenly decreased by 35 mmHg or more. In addition to the mean systemic arterial pressure, the cardiac output, the mean pulmonary arterial pressure, the central venous pressure and the pulmonary capillary wedge pressure decreased in response to each haemorrhage. The recovery of the systemic and pulmonary arterial pressure was slower and/or less efficient after the second haemorrhage, due to a less pronounced increase of the vascular resistance. Relative bradycardia, in association with the abrupt fall of the mean systemic arterial pressure, was more apparent during the first haemorrhage. The plasma levels of vasopressin, renin activity and angiotensin II were increased by each blood removal, but the vasopressin response to the second haemorrhage was significantly reduced. The plasma noradrenaline concentration was slightly and transiently elevated only in response to the second haemorrhage. The concentration of neuropeptide Y-like immunoreactivity in plasma was unaffected by both haemorrhages. It is suggested that the reduced and delayed increase in the systemic vascular resistance, accompanied by impaired recovery of the arterial pressure, and the relative absence of 'bleeding bradycardia', during the second haemorrhage, were due to the diminished vasopressin response.     

Regulation and function of the FGF23/klotho endocrine pathways

Calcium (Ca(2+)) and phosphate (PO(4)(3-)) homeostasis are coordinated by systemic and local factors that regulate intestinal absorption, influx and efflux from bone, and kidney excretion and reabsorption of these ions through a complex hormonal network. Traditionally, the parathyroid hormone (PTH)/vitamin D axis provided the conceptual framework to understand mineral metabolism. PTH secreted by the parathyroid gland in response to hypocalcemia functions to maintain serum Ca(2+) levels by increasing Ca(2+) reabsorption and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] production by the kidney, enhancing Ca(2+) and PO(4)(3-) intestinal absorption and increasing Ca(2+) and PO(4)(3-) efflux from bone, while maintaining neutral phosphate balance through phosphaturic effects. FGF23 is a recently discovered hormone, predominately produced by osteoblasts/osteocytes, whose major functions are to inhibit renal tubular phosphate reabsorption and suppress circulating 1,25(OH)(2)D levels by decreasing Cyp27b1-mediated formation and stimulating Cyp24-mediated catabolism of 1,25(OH)(2)D. FGF23 participates in a new bone/kidney axis that protects the organism from excess vitamin D and coordinates renal PO(4)(3-) handling with bone mineralization/turnover. Abnormalities of FGF23 production underlie many inherited and acquired disorders of phosphate homeostasis. This review discusses the known and emerging functions of FGF23, its regulation in response to systemic and local signals, as well as the implications of FGF23 in different pathological and physiological contexts.     

Atrial natriuretic hormone, the renin-aldosterone axis, and blood pressure-electrolyte homeostasis

The renin-angiotensin-aldosterone axis exerts major control over sodium and potassium balance and arterial blood pressure. These three functions are continuously regulated by changes in angiotensin II and aldosterone levels in response to wide variations in dietary intake of sodium and potassium. In addition, changes in intrarenal physical factors cause changes in the supply of distal tubular sodium that, in turn, work to determine sodium and potassium excretion and to modulate the release of renal renin. However, certain aspects of sodium homeostasis cannot be fully explained either by the activity of the renin system or by intrarenal physical factors, and this has led investigators to search for other natriuretic hormonal mechanisms. Recently, it has become clear that atrial tissue contains a group of peptides, at least one of which is probably secreted as a regulatory hormone. In animals, these atrial peptides produce immediate, marked natriuresis associated with a rise in glomerular filtration rate (but no alteration of total renal flow) and a simultaneous decrease in arterial blood pressure. Atrial peptides also inhibit renal renin secretion and adrenal cortical secretion of aldosterone, and they oppose the vasoconstrictive action of angiotensin II. One of these atrial peptides may therefore be the long-sought natriuretic hormone, though in a different form and shape than was envisioned. The fact that atrial peptide works to oppose the renin system at four points suggests that this new hormone could have a major complementary role in long-term regulation of blood pressure and electrolyte homeostasis. In this construction the renin system primarily defends sodium balance and blood pressure, with the atrial hormone having an increasing counter-influence in situations involving high blood pressure or sodium surfeit. We can soon expect to learn more about this atrial hormone, including which peptide is the active circulating hormone, what induces or inhibits its release, and what part it plays in cardiovascular diseases.     

Myogenic vascular regulation in skeletal muscle in vivo is not dependent of endothelium-derived nitric oxide.

The hypothesis, based on in vitro experiments on large conduit arteries, that endothelium-derived nitric oxide is a mediator of vascular myogenic reactivity was tested in cat gastrocnemius muscle in vivo. This was done by comparing, in the absence and presence of effective endothelium-derived nitric oxide blockade by the specific inhibitors NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester, myogenic responses in defined consecutive vascular sections to dynamic vascular transmural pressure stimuli, to arterial occlusion (reactive hyperaemia), and to arterial pressure changes (autoregulation of blood flow and capillary pressure). The results demonstrated that the myogenic vascular reactivity to quick ramp transmural pressure stimuli was not attenuated by endothelium-derived nitric oxide blockade, but rather reinforced. The amplitude of the reactive hyperaemia response was unaffected by endothelium-derived nitric oxide blockade, but its duration was shortened because of faster myogenic constriction, especially of large-bore arterial resistance vessels greater than 25 microns, in the recovery phase. Both the improved myogenic responsiveness to transmural pressure stimuli and the shortening of the reactive hyperaemia by endothelium-derived nitric oxide blockade suggested that endothelium-derived nitric oxide released in vivo acts as a 'metabolic' factor which certainly does not improve, but rather depresses myogenic vascular reactivity. Autoregulation of blood flow and capillary pressure were well preserved in the presence of endothelium-derived nitric oxide blockade. It was concluded from the results of these multifaceted tests that myogenic vascular regulation in skeletal muscle in vivo seems independent of endothelium-derived nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood flow restriction: the metabolite/volume threshold theory

Traditionally it has been thought that muscle hypertrophy occurs primarily from an overload stimulus produced by progressively increasing an external load using at least 70% of one’s concentric one repetition maximum (1RM). Blood flow restricted exercise has been demonstrated to result in numerous positive training adaptions, specifically muscle hypertrophy and strength at intensities much lower than this recommendation. The mechanisms behind these adaptions are currently unknown but a commonly cited concept is that acute elevations of systemic hormones, specifically growth hormone (GH), play a large role with resistance training induced muscle hypertrophy, possibly through stimulating muscle protein synthesis (MPS). We hypothesize that the alterations in the intramuscular environment which results in the rapid recruitment of FT fibers, is the large driving force behind the skeletal muscle hypertrophy seen with blood flow restriction, whereas the external load and systemic endogenous hormone elevations may not be as important as once thought. It is further hypothesized that although skeletal muscle hypertrophy can be achieved at low intensities without blood flow restriction when taken to muscular failure, the overall volume of work required is much greater than that needed with blood flow restriction.     

Hypothyroidism and the heart

The cardiovascular system is sensitive to the action of thyroid hormones, and thyroid dysfunction causes a wide spectrum of cardiovascular changes. The effect of overt hypothyroidism on the cardiovascular system has long been recognised. Nowadays, the clinical presentation of cardiovascular symptoms related to hypothyroidism is only rarely observed due to early diagnosis of hypothyroidism by easily available thyroid-stimulating hormone assays. Overt hypothyroidism causes changes in such parameters of cardiovascular function as heart rate, left ventricular systolic and diastolic function, blood, arterial pressure and systemic vascular resistance. During the last years, there has been increasing evidence that subclinical hypothyroidism may also impair the cardiovascular system. This review discusses the effect of hypothyroidism on the cardiovascular system.     

Sweet taste receptor in the hypothalamus: a potential new player in glucose sensing in the hypothalamus

The hypothalamic feeding center plays an important role in energy homeostasis. The feeding center senses the systemic energy status by detecting hormone and nutrient levels for homeostatic regulation, resulting in the control of food intake, heat production, and glucose production and uptake. The concentration of glucose is sensed by two types of glucose-sensing neurons in the feeding center: glucose-excited neurons and glucose-inhibited neurons. Previous studies have mainly focused on glucose metabolism as the mechanism underlying glucose sensing. Recent studies have indicated that receptor-mediated pathways also play a role in glucose sensing. This review describes sweet taste receptors in the hypothalamus and explores the role of sweet taste receptors in energy homeostasis.     

Impairment during marked hypotension of the plasma volume control in hemorrhage

During hypovolemia extravascular fluid is transferred across the capillaries into the circulation in order to restore blood volume. Several studies have shown that this process. which mainly occurs in skeletal muscle, effectively can compensate for the blood loss. The present investigation performed in the cat strongly indicates, however. that this vital compensatory mechanism is inactivated in situations of pronounced hypovolemia leading to hypotension levels of 30–40 mmHg, i.e. when the need for refill of the circulatory system is most in demand. It is suggested that the cessation of fluid transfer from skeletal muscle to blood during marked hypotension is causally linked to the evoked pronounced reduction of blood flow, due partly to the much reduced perfusion pressure and partly to the marked vasoconstriction. Pronounced vasoconstriction in the hemodynamically important vascular bed of skeletal muscle is obviously an essential part of the necessary resistance response evoked in the systemic circulation in order to avoid circulatory collapse already in the early phase of a large blood loss. However, the chances for the organism to survive is minimized if the vasoconstriction leads to impairment of the mechanisms for plasma volume regulation.