Bradykinin microinjection in the paratrigeminal nucleus triggers neuronal discharge in the rat rostroventrolateral reticular nucleus

A small collection of neurons in the dorsal lateral medulla, the paratrigeminal nucleus (Pa5), projects directly to the rostroventrolateral reticular nucleus (RVL). Bradykinin (BK) microinjections in the Pa5 produce marked pressor responses. Also, the Pa5 is believed to be a component of the neuronal substrates of the somatosensory response and the baroreflex arc. Considering the developing interest in the functional physiology of the Pa5, the present study was designed to characterize RVL neuronal activity in response to BK microinjections in the Pa5 as well as to phenylephrine-induced blood pressure increases in freely behaving rats. Of the 46 discriminated RVL neurons, 82% responded with a 180% mean increase in firing rate after BK application to the paratrigeminal nucleus, before the onset of the blood pressure increase. Thirty (79%) of the RVL BK-excited neurons were baroreceptor-inhibited units that responded with a 30% decrease in firing rate in response to a phenylephrine-produced increase of blood pressure. Twenty-seven (71%) units of the latter population displayed cardiac-cycle-locked rhythmic activity. The findings demonstrate a BK-stimulated functional connection between the Pa5 and RVL that may represent the neural pathway in the BK-mediated pressor response. This pathway may be relevant to baroreflex mechanisms since it relates to cardiovascular pressure-sensitive neurons.     

Dopaminergic modulation of salt sensitivity in patients with essential hypertension

The present study was designed to investigate the possible role of dopaminergic mechanisms in contributing to the pathogenesis of hypertension in salt sensitive patients. Eighteen patients with essential hypertension were studied while under a diet ranging from low salt to high salt, which enabled a classification in "salt-sensitive" (SS) and "nonsalt-sensitive" (NSS) groups based on a tentative criteria of a 10% increase of mean blood pressure with high salt diet. The SS patients showed reduced urinary excretion of sodium as compared with that from NSS patients. Urinary norepinephrine excretion in all patients with salt loading was suppressed, but urinary excretion of epinephrine showed a tendency to increase in SS patients after salt loading. Urinary excretion of dopamine increased in NSS patients with salt loading, but did not change in SS patients. To further evaluate the role of dopaminergic mechanisms in salt-sensitive hypertension, metoclopramide, a dopamine antagonist, was injected intravenously to all patients. With salt loading, plasma aldosterone levels increased after injection of metoclopramide in NSS patients, but did not change in SS patients. These results suggest that salt-sensitive hypertension is modulated by dopaminergic activity, which in turn is attenuated in SS patients. Decreased dopaminergic activity induced sodium retention both by a direct effect on the kidney as well as indirectly via relatively increased aldosterone secretion. Both mechanisms would help to increase intravascular volume and blood pressure in salt-sensitive hypertension.     

Thrombopoietic activity induced by blood withdrawal and administration of antithrombocyte serum in nephrectomized rats. Role of kidneys in the production of thrombopoietin

The thrombopoietic serum activity was examined in rats during thrombocytopenia produced by bleeding or after treatment with antithrombocyte serum (ATS). 6 hours after both treatments the thrombopoietic activity of the serum, i.e. its content of thrombopoietin, is increased. After the ATS treatment of nephrectomized animals a similar increase of thrombopoietic activity as in normal animals could be achieved. In contrast to that, no similar increase of thrombopoietic activity was observed in nephrectomized animals after blood loss. According to the results of the authors the increase of thrombopoietic activity produced by different stimuli can be attributed to different mechanisms.     

Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension.

Cardiovascular (systolic and diastolic blood pressure, heart rate), antihyperlipidemic (tryglycerides, total cholesterol and lipoprotein fractions), antioxidant (glutathione peroxidase--GPx, and superoxide dismutase--SOD), diuretic/saluretic and hypoglycemic activity of 98% pure oleanolic (OA) and ursolic (UA) acid were studied in Dahl salt-sensitive (DSS), insulin resistant rat model of genetic hypertension. Both OA and UA displayed low toxicity, with LC50 0.10 and 0.95 mg/ml, respectively. Although both triterpenoids did not have direct hypotensive effect, after 6-week application in a daily dose 60 mg/kg b.w., i.p., they prevented the development of severe hypertension. The antihypertensive effect was attributed to their potent diuretic-natriuretic-saluretic activity; direct cardiac effect (heart rate decrease by 34% and 32%, respectively); antihyperlipidemic (more than two times decrease of LDL and triglycerides); antioxidant (GPx increase by 12% and 10%, respectively; SOD increase by 12% and 22%, respectively), and hypoglycemic (blood glucose decrease by 20% and 50%, respectively) effects on the DSS rats. Except for the antihyperlipidemic effects, the other described above in vivo antihypertensive effects of OA and UA are reported for the first time and the underlying mechanisms are currently under investigation.     

Effect of acute hypoxia on the renin and erythropoietin activities of the blood serum in rats

A comparative study of renin and erythropoietin content in the blood serum of rats with "endocrine" kidneys and changes in their activity following the action of specific erythropoietic stimulus (4-hour hypoxia) has been conducted. The presence of "endocrine" kidneys increased renin and erythropoietin activity in such animals. Acute hypoxia produced further increase in erythropoietin titre in the blood serum, with renin remaining at the same level. Possible differences in the mechanisms of renin and erythropoietin biogenesis in the kidneys are considered.     

Effect of the long-term exposure of the isolated myometrium from nonpregnant rats to serum from pregnant women on its contractile activity and the beta-adrenergic reactivity

Pregnant women's blood serum (the whole as well as 50- and 100-diluted) did not alter parameters of spontaneous motility, i.e. it did not affect the uterus myocytes' spontaneous motility, whereas the whole or 50-diluted serum raised considerable the rat myometrium's beta-adrenoreaction. The data obtained suggest that the beta-adrenoreaction of the rat uterus' myocytes increases after a prolonged contact with pregnant women's blood serum which may be due to the beta-adrenoreceptor synthesis activation and to an increase in their concentration because of diffusion from the blood serum. This suggests existence of humoral mechanisms of the myometrium beta-adrenoreaction regulation, the mechanisms creating the optimum uterus' contractile activity.     

Endogenous reductions in N-methyl-d-aspartate receptor activity inhibit nitric oxide production in the anoxic freshwater turtle cortex

Increased nitric oxide (NO) production from hypoxic mammalian neurons increases cerebral blood flow (CBF) but also glutamatergic excitotoxicity and DNA fragmentation. Anoxia-tolerant freshwater turtles have evolved NO-independent mechanisms to increase CBF; however, the mechanism(s) of NO regulation are not understood. In turtle cortex, anoxia or NMDAR blockade depressed NO production by 27+/-3% and 41+/-5%, respectively. NMDAR antagonists also reduced the subsequent anoxic decrease in NO by 74+/-6%, suggesting the majority of the anoxic decrease is due to endogenous suppression of NMDAR activity. Prevention of NO-mediated damage during the transition to and from anoxia may be incidental to natural reductions of NMDAR activity in the anoxic turtle cortex.     

Prevention of hypertension and maintenance of normotension in spontaneously hypertensive rats is dependent on continuous severe dietary sodium restriction

Spontaneously hypertensive rats were placed on a very low (9 mumol/g) or control (101 mumol/g) sodium diet at birth or 4 weeks of age. These diets were continued to 16 weeks of age, or at 10 weeks were increased from 9 to 26 or 101 mumol/g. Sodium restriction initiated up to 4 weeks of age and continued to 16 weeks of age severely retarded growth, prevented the development of hypertension, and reduced effective sympathetic activity as assessed by the response of blood pressure to ganglionic blockade. Only a small increase in sodium intake at 10 weeks of age (to 26 mumol/g or more) resulted in a marked increase in growth rate, an elevation of blood pressure, and a return of the response to ganglionic blockade towards normal. These data indicate that very severe sodium restriction must be continuous to maintain decreased sympathetic activity and normal blood pressure in spontaneously hypertensive rats. It appears that severe dietary sodium restriction suppresses one or more of the mechanisms involved in normal growth and development of hypertension in spontaneously hypertensive rats, but these mechanisms may still proceed once the sodium intake is increased.     

Effect of chronic ethanol consumption on emotional stress in the white rat

Chronic pain emotional stress (PES), paired action of the white noise and electric skin stimulation and chronic (during 7 months) ethanol consumption in white rats were shown to act in the same direction. Hypertension, decrease of respiratory rate and increase of Hildebrandt index were observed as a result of PES, ethanol consumption, and especially under PES during ethanol consumption. Ethanol consumption by the animals led to their growth retardation and increase of the spleen and heart mass. Accidental thymus involution was noted both under ethanol consumption and PES. Activation of lipid peroxidation and decrease of superoxide dismutase activity (of its mitochondrial form especially) as well as of Na+,K+-ATP-ase activity were observed in brain homogenates of the rats after PES, while the general ATP-ase activity remained unchanged. An increase of triiodothyronine level and the tendency to thyroxine level increase as well as a decrease of superoxide dismutase activity were observed in the blood serum of these animals. A tendency towards lipid peroxidation level decrease and to brain superoxide dismutase activity increase, as well as blood antioxidation activity increase (evaluated by transferrin and coeruloplasmin contents and by serum superoxide dismutase activity) and a decrease of thyroxine level were observed as a result of ethanol consumption. The mechanisms are discussed of the "anti-stress" action of short-term ethanol consumption and of the action of its chronic consumption, additive to PES.     

The influence of bicycle ergometer work and oral glucose administration on the muscle hexokinase activity in man (author's transl)]

The influence of orally administered carbohydrates and bicycle work on muscle hexokinase activity, blood glucose, and serum insulin levels were studied in 6 young men. Continuously administered glucose of a total amount of 150 g caused a significant increase in hexokinase activity within 3 hrs. Working at a load of 155 to 195 Watt led to an initial increase of hexokinase activity. At the end of the working period hexokinase activity had fallen to resting values. The possible mechanisms of action are discussed.     

The mechanism of nonachlazine on cardiac activity and blood supply]

Nonachlazine (10 mg/kg intravenously) exerted a two-phase influence on the heart activity. The short phase of the weakening of the heart activity gave place to the intensive increase in the cardiac output and the contractility of the myocardium. An increase in the blood supply and heart activity coincided in time with the accumulation of the quantity of noradrenaline and with increase in the phosphorylase "a" activity. Beta-adrenoblockers prevented the development of the effect in question. It is assumed that the efficacy of nonachlazine during ischemic heart disease was connected with its capacity to activate the adrenergic mechanisms of the glycogenolysis regulation leading to the switching of the myocardial metabolism to the anaerobic route of energy release.     

Heparin potentiation of 3T3-adipocyte stimulated angiogenesis: mechanisms of action on endothelial cells

We have examined the cellular mechanisms by which heparin potentiates the ability of 3T3-adipocytes to stimulate the formation of new blood vessels. Both anticoagulant and non-anticoagulant heparin species enhanced the angiogenic activity of adipocyte-secreted products in the chick chorioallantoic membrane assay, indicating that the angiotropic effect of this glycosaminoglycan is independent of its effect on the coagulation cascade. Heparin alone was unable to produce a neovascular response. The ability of heparin to modulate three endothelial functions in vitro thought to be related to angiogenesis were examined: protease activity, motility, and mitogenesis. Heparin caused a 100% increase in the adipocyte-induced stimulation of endothelial cell plasminogen activator activity and motility, but had no effect on proliferation. The enhancement of plasminogen activator and chemoattractant activities had a similar ED50 (1-2 micrograms/ml) and optimum dose (10-30 micrograms/ml). When we examined the direct effect of heparin on the activity of two distinct plasminogen activator enzymes--urokinase and tissue-type--a dual action of heparin was observed: tissue-type enzyme activity was stimulated 100% by heparin at 10 micrograms/ml, whereas urokinase activity was inhibited by 77% at this dose. These data suggest that heparin potentiates angiogenesis in vivo by stimulating endothelial cell plasminogen activator, motility, or both. Our results further suggest that for adipocyte-induced blood vessel formation, in contrast to other angiogenesis systems, heparin does not appear to affect the mitogenic activity.     

Effect of air exposure on nitrogen metabolism in the crab Cancer pagurus.

In C. pagurus exposed to air for 18 h, blood ammonia content decreased within the 2 first hours, then increased at a relatively constant rate (25 microM/h); blood urate content increased at a lower rate (10 microM/h) and a classical blood acidosis was observed. In the cheliped muscle, a transient 22% decrease in GDH activity for ammonia formation and a 48% increase in GDH activity in the reverse reaction (glutamate synthesis) occurred following 6 and 12 h of emersion, respectively. Changes in LDH activity, used as an indicator of anaerobic potential of muscle, were not observed, except for an 18% increase in crabs exposed to air for 24 h. The increase in blood urate content, not known as a response to emersion in decapods, appeared to be different from that observed in response to hypoxia. The relatively low blood ammonia overload and the GDH increased activity for glutamate synthesis suggested that part of the produced ammonia was stored under a bound form in some tissues. The response of C. pagurus to air exposure is discussed on account of the Storey and Storey ('90) theory.     

Changes in the leukocyte phagocytic activity of donor blood after its UV irradiation. II. Simulation of the effect of the autotransfusion of UV-irradiated blood

The UV-irradiated blood of healthy adults was supplemented with non-irradiated blood in the ratio 1:10. The phagocytic activity (PhA) of monocytes and granulocytes was seen to increase markedly in the whole mixture of blood. In this case the rise of PhA was pronounced 1.4-1.7 times as much as in the case of the non-supplemented, directly UV-irradiated blood. The enhancement of PhA depends on its initial level and may occur simultaneously with structural changes of the cell surface components. It seems reasonable to propose that PhA stimulation may be one of the earliest mechanisms in immunocorrection by UV-irradiated blood therapy.     

Lysosomal apparatus of some body tissues in hemorrhage-induced hypoxia ]

The experiments on 40 Wistar male rats with acute circulatory-hemic hypoxia induced by hemorrhage in amount of 15-20% of circulating blood volume were carried out to study the state of lysosomal apparatus of the liver and lung tissues as to changes in activity of acid phosphatase (AP), a marker enzyme of lysosomes. In the case of such a hemorrhage the common activity of AP decreased by 37% in the liver tissue and by 41% in the lung tissue, the free activity increased by 30% and 25%, and bound activity decreased by 84 and 70% in homogenates of the corresponding tissues. Under these conditions the activity of the above lysosomal enzyme in blood plasma became five times as higher as control. A conclusion is made concerning the circulatory-hemic hypoxia influence on the lysosomal membrane's structures of organ's tissues cells (as one can judge by the example of liver and lungs), which is observed in an increase of permeability of lysosome membrane and causes a sharp increase of AP enzymia in blood plasma.     

Contribution of captopril thiol group to the prevention of spontaneous hypertension

We aimed to compare the effect of angiotensin converting enzyme (ACE) inhibitors captopril (containing thiol group) and enalapril (without thiol group) on the development of spontaneous hypertension and to analyze mechanisms of their actions, particularly effects on oxidative stress and NO production. Six-week-old SHR were divided into three groups: control, group receiving captopril (50 mg/kg/day) or enalapril (50 mg/kg/day) for 6 weeks. At the end of experiment, systolic blood pressure (SBP) increased by 41 % in controls. Both captopril and enalapril prevented blood pressure increase, however, SBP in the captopril group (121+/-5 mmHg) was significantly lower than that in the enalapril group (140+/-5 mmHg). Concentration of conjugated dienes in the aorta was significantly lower in the captopril group compared to the enalapril group. Captopril and enalapril increased NO synthase activity in the heart and aorta to the similar level. Neither captopril nor enalapril was, however, able to increase the expression of eNOS. Both ACE inhibitors increased the level of cGMP. However, cGMP level was significantly higher in the aorta of captopril group. We conclude that captopril, beside inhibition of ACE, prevented hypertension by increasing NO synthase activity and by simultaneous decrease of oxidative stress which resulted in increase of cGMP concentration.     

12周太极拳运动对中老年轻度高血压患者微血管反应性的影响及机制*

目的:研究12周太极拳运动对中老年轻度高血压患者微血管反应性的影响,并探讨微血管反应性变化的机制。方法:将30名轻度高血压患者分为运动组(53.8±6.3岁)和对照组(52.6±7.5岁),两组人数及性别比例相同。运动组进行12周的太极拳运动,对照组保持原先的生活方式且不做其它规律性的体育运动。两组受试者分别于运动干预前、第6周和第12周结束后进行微血管反应性、血压及血清一氧化氮含量 、一氧化氮合酶活性测试。结果:试验前,两组受试者各指标的基础值均无显著差异(P＞0.05)。运动组,第6周微血管反应性、收缩压、舒张压、一氧化氮含量、一氧化氮合酶活性较基础值无显著变化(P＞0.05),第12周微血管反应性、一氧化氮含量和钙依赖型一氧化氮合酶活性较基础值及对照组显著升高(P＜0.05),收缩压和舒张压较基础值和对照组显著下降(P＜0.05)。对照组,第6周、第12周各指标较基础值均无显著变化(P＞0.05)。结论:12周太极拳运动能提高中老年轻度高血压患者微血管反应性、降低血压,并能提高患者一氧化氮含量、钙依赖型一氧化氮合酶活性,内源性一氧化氮生成增加是太极拳运动提高高血压患者微血管反应性的生物学机制之一。     

Assessment of the changes in regulatory systems of human's skin blood flow during local heating

The mechanisms of thermal regulation of skin blood flow during local heating to 35, 40 and 45 'C have been studied by the method of laser Doppler flowmetry in healthy volunteers. To estimate the state of microvascular bed the continuous wavelet-transform spectral analysis has been used. The amplitudes of fluxmotions in the range of blood flow active modulation significantly increase during local heating to 35 degrees C. The amplitudes of blood flow oscillations in the ranges of cardiorhythm and respiratory rhythm increase during local heating to 40 degrees C. The high amplitude oscillations in the range of myogenic activity are maintained. The amplitude of oscillations in the range of endothelial activity distinctly decreases and the oscillations in the range of neurogenic activity are inhibited. Local heating to 45 degrees C results in a significant decreasing of the oscillation amplitudes in the range of myogenic activity, and the amplitudes of cardio- and respiratory spectral components amount to their peak values among the temperatures of local heating under study.     

The effect of copper supplementation on red blood cell oxidizability and plasma antioxidants in middle-aged healthy volunteers

A multicenter European study (FoodCue) was undertaken to provide data on the significance of increased dietary copper as a pro-oxidant or antioxidant in vivo. The present work describes the effect of Cu supplementation on (2,2'-azo-bis(2-amidinopropane) hydrochloride (AAPH)-induced red blood cell oxidation in middle-aged people. Double-blinded copper supplementation was achieved in 26 healthy volunteers (50-70 years) with pills containing 3 mg CuSO(4), 3 mg Cu glycine chelate (CuG) and 6 mg CuG. Each 6 week supplementation period was preceded and followed by 6 weeks of washout (WO) on placebo. The results show significant increases in time necessary to achieve 50% hemolysis (LT(50)) after 3CuSO(4) and 6CuG compared with values after WO periods. Cu supplementation did not increase the levels of (Cu,Zn)SOD activity in red blood cells. Resistance to hemolysis was significantly and positively correlated (r =.30, p <.01) with alpha- and beta-carotene content in the plasma. Together, these data suggest that intake of copper as high as 7 mg/d has no pro-oxidant activity and may rather result in protection of red blood cells against oxidation. The decreased oxidizability of red blood cells did not result from increased (Cu,Zn)SOD activity and may occur through other mechanisms such as changes in membrane antioxidant content.