Correction of arterial pressure in rats with hereditary hypertension by altering catecholamine metabolism in early ontogeny

In a newly developed rat strain with inherited stress-sensitive arterial hypertension (ISSAH) an attempt was made to reduce arterial blood pressure by L-DOPA injections during a short time period of the early ontogenesis. It was shown that L-DOPA injections to rats on days 7-9 or 14-16 of life had no effect. The same procedure performed on 21-23 or 21-25-day-old rats was followed by a decrease in the basal and stress-induced arterial blood pressure levels, measured in adulthood. Injections of dopamine-beta-hydroxylase inhibitor (FLA-59) with parallel L-DOPA administration completely blocked the blood pressure decreasing effect. It can be suggested that injections of L-DOPA in the 4th week of post-natal life reduce the blood pressure level in ISSAH rats by enhancing the rate of brain noradrenaline biosynthesis.     

Effect of chronic stress during prepubertal period of life on development of inherited arterial hypertension

The immediate and long-lasting effects of environmental stress during prepubertal life on arterial blood pressure (AP) were studied in rats with inherited stress-induced arterial hypertension (ISIAH) and normotensive Wistar rats. Two models of chronic stress (the 21st-32nd postnatal days) were used: repeated handling and unpredictable stress of daily exposures to a variety of mild physical or psychoemotional stressors. Chronic prepubertal stress did not affect the basal or stress-induced AP levels in young or adult Wistar rats. In ISIAH rats, chronic stress during the early phase of hypertension development did not accelerate its formation and did not augment its manifestation in adults. Moreover, the basal AP was decreased in young and adult ISIAH rats exposed to prepubertal stress as compared to the age-matched controls. AP elevation under acute stress conditions was lower in young ISIAH rats exposed to unpredictable stress. No long-lasting effect of prepubertal stress on acute stress-induced AP elevation in adults was found. The conclusion was drawn that moderate physical and psychoemotional training at prehypertensive stage can positively affect the development of inherited arterial hypertension.     

Chronic stress increases the reactivity of central depressor mechanisms]

The activity of noradrenergic system of lateral hypothalamus and hemodynamics were studied during acute restraint in chronically stressed and control rats. Arterial blood pressure in rest was negatively proportional to basal norepinephrine concentration in dialysate of lateral hypothalamus. Animals with high increase of norepinephrine levels in dialysate during acute stress had rapid return of arterial blood pressure to basal values while stress-induced hypertension in the beginning of restraint was the same as in rats with low increase of norepinephrine levels. Data obtained show the depressor role of noradrenergic system of lateral hypothalamus. The enhanced reactivity of noradrenergic depressor system may be one of the mechanisms providing cardiovascular adaptation to stress.     

Effect of chronic social stress on nitric oxide synthesis and vascular function in rats with family history of hypertension

Genetic predisposition and psychosocial stress are known risk factors in the aetiology of hypertension. The aim of this study was to investigate the as yet unknown role of nitric oxide (NO) in mechanisms of social stress-induced hypertension in rats with a family history of hypertension. Male adult rats used in the study were offspring of normotensive (Wistar) dams and spontaneously hypertensive sires. The rats were exposed to 6-week crowding stress (5 rats/cage, 200 cm2/rat). Control rats were kept four per cage (480 cm2/rat). Blood pressure was determined non-invasively on the tail. Basal blood pressure of all rats was 131 +/- 2 mm Hg. Crowding stress increased significantly blood pressure (p < 0.02 vs. basal value). Crowding had no influence on NO synthase activity in the left ventricle, adrenal glands and kidney. However, crowding stress reduced significantly NO synthase activity in the aorta by 37% (p < 0.01 vs. control). Acetylcholine-induced relaxation and noradrenaline-induced vasoconstriction of the femoral artery were reduced in stressed rats by 58% (p < 0.001) and 41% (p < 0.003), respectively. On balance then, the results indicate that chronic social stress produced by crowding was associated with reduced vascular NO synthesis and altered vascular function in adult borderline hypertensive rats of normotensive mothers.     

Cardiovascular peculiarities in hypertensive rats (Hsiah strain) after antihypertensive drug intervention during juvenile period of life

Treatment with different types of antihypertensive drugs during second month age has not prevented development of arterial hypertension and myocardial hypertrophy in the adult rats with inherited stress-induced arterial hypertension. At 6 months of age, the 11% attenuation of basal blood pressure has beet achieved only in the rats treated with angiotensin-converting enzyme inhibitor enalapril. Nevertheless, they expressed the most pronounced left ventricular hypertrophy. The unfavorable tissue and ultrastructural abnormalities were revealed in the myocardium of the rats which received the alpha1-adrenoceptor blocker terazosin. The delayed effects of losartan (angionetsin II receptor antagonist) and corinfar (calcium channel antagonist) on the myocardial structure were inessential.     

头端延髓腹外侧区注射5—羟色胺对应激性高血粘度...

Experiments were carried out on 62 wistar rats. The hyperviscosity and elevation of blood pressure were induced by hanging and restraining the rats with their four limbs tied on a frame. It was found that microinjection of 5-HT (25 micrograms/10 microliters) into the 4th ventricle of the brain or bilateral microinjection of 5-HT (4 micrograms/0.5 microliters/site) into rostral ventrolateral medulla (rVLM) reduced stress-induced hyperviscosity (p < 0.01) and elevation of blood pressure (p < 0.01). The effect of 5-HT injected into the 4th ventricle or rVLM was blocked by bilateral microinjection of cinanserine (4 micrograms/0.5 microliter/site) into rVLM. These results suggest that microinjection of 5-HT into 4th ventricle and rVLM could reduce stress-induced hyperviscosity and elevation of blood pressure and these effects were probably mediated via 5-HT receptors in the rVLM.     

Spectral analysis of muscle sympathetic nerve activity in heat-stressed humans

Whole body heating increases muscle sympathetic nerve activity (MSNA); however, the effect of heat stress on spectral characteristics of MSNA is unknown. Such information may provide insight into mechanisms of heat stress-induced MSNA activation. The purpose of the present study was to test the hypothesis that heat stress-induced changes in systolic blood pressure variability parallel changes in MSNA variability. In 13 healthy subjects, MSNA, electrocardiogram, arterial blood pressure (via Finapres), and respiratory activity were recorded under both normothermic and heat stress conditions. Spectral characteristics of integrated MSNA, R-R interval, systolic blood pressure, and respiratory excursions were assessed in the low (LF; 0.03-0.15 Hz) and high (HF; 0.15-0.45 Hz) frequency components. Whole body heating significantly increased skin and core body temperature, MSNA burst rate, and heart rate, but not mean arterial blood pressure. Systolic blood pressure and R-R interval variability were significantly reduced in both the LF and HF ranges. Compared with normothermic conditions, heat stress significantly increased the HF component of MSNA, while the LF component of MSNA was not altered. Thus the LF-to-HF ratio of MSNA oscillatory components was significantly reduced. These data indicate that the spectral characteristics of MSNA are altered by whole body heating; however, heat stress-induced changes in MSNA do not parallel changes in systolic blood pressure variability. Moreover, the reduction in LF component of systolic blood pressure during heat stress is unlikely related to spectral changes in MSNA.     

Effect of ethanol on heart rate and blood pressure in nonstressed and stressed rats

The effect of ethanol on the cardiovascular system (ECG, heart rate, blood pressure) was studied in anesthetized, nonstressed or stressed rats. In anesthetized rats, ethanol showed no effect on heart rate or ECG. In nonstressed rats, ethanol sedated the animals but increased heart rate significantly. This ethanol induced tachycardia seemed the result of a direct stimulation of the sympathetic nerves to the heart. Blood pressure was not significantly affected by ethanol in these nonstressed rats. In stressed rats, marked behavioral excitation and significant increases in heart rate and blood pressure were noted. Ethanol pretreatment calmed the animals considerably during restraint. Ethanol did reduce slightly the stress-induced tachycardia but markedly reduced or antagonized stress-induced blood pressure increases. No major changes in the ECG were noted during these studies with the exception of a few individual animals which showed pathologic ECG responses to ethanol. These data show that ethanol affects cardiovascular functions differently in anesthetized, nonstressed or stressed rats, and that ethanol can significantly reduce or antagonize stress-induced behavioral excitation, tachycardia and hypertension.     

Noradrenaline synthesis during the first week of life and development of inherited stress-induced arterial hypertension in rats

Increasing of the noradrenaline synthesis with daily i.p. administration of synthetic noradrenaline precursor DL-Threo on the 21-25th day of life of the rats with inherited stress-induced arterial hypertension (ISIAH) resulted in a drop of basal and stress-induced blood pressure in adult animals with no changes in response of the hypothalamic-pituitary-adrenocortical system (HPAS). Reduction of the noradrenaline synthesis with daily i.p. administration of dopamine-hydroxylase inhibitor FLA-57 in 21-25th day old Wistar rats induced no arterial hypertension in adults but decreased their adrenocortical response to emotional stress. Noradrenaline deficit in the brain structures on the 4th week of life in rats seems to be associated with arterial hypertension only in presence of genetic defect determining this pathology. Changes in adult HPAS function due to shortage of noradrenaline in the brain in the end of the 1st month of life do not depend on hypertension.     

Characteristics of Basic Parameters of the Hormonal Function of the Adrenal Cortex and Its Modification in Rat Ontogenesis

The stress-reactivity of the pituitary-adrenocortical system (PAS) as assessed by the dynamics of the blood corticosterone level changes was studied in rats administered with cortisol at different periods of their pre- and postnatal ontogenesis. The participation of the activation and deactivation mechanisms in this process was estimated by means of a mathematical modeling, using the basic parameters of hormonal wave. It is established that in the one-month old rat pups born from mothers injected with cortisol from the day 14 to 18 of pregnancy, the basal and stress-evoked PAS activity was not essentially changed, whereas the adult animals demonstrated a faster decrease of the stress-induced corticosterone level. Injection of cortisol at the early neonatal ontogenesis (1–5 day of life) decreased the basal and stress-induced corticosterone levels at the morning hours in one-month old rats, whereas in adult rats it increased the PAS stress-reactivity. Injection of cortisol in the late neonatal ontogenesis, i.e., during the period of formation of the sensory systems (opening of the ears, eyes, maximal motor activity) resulted predominantly in changing the time of completion of the stress-induced hormonal response that became longer than in control animals of the same age. With the aid of mathematical modeling, we have found that at the early neonatal period of development the hormonal exposure mainly increases the rate of PAS activation, whereas injection of glucocorticoids at the late neonatal period changes PAS regulation by a feedback mechanism, thus decreasing the rate of system inactivation and increasing the time of completion of PAS stress-induced reaction. It is concluded that the phenotypic reorganization of PAS stress-reactivity by exogenous corticosteroids depends on the time of their action on development of the excitatory and inhibitory mechanisms during the critical periods of their formation.     

Neuropeptide Y reverses chronic stress-induced baroreflex hypersensitivity in rats

Chronic stress, as a risk factor for cardiovascular diseases, has been reported to result in elevated plasma neuropeptide Y (NPY) and be highly associated with abnormal cardiac autonomic function. This study aimed to explore the effect of NPY on the chronic stress-induced abnormal baroreceptor reflex sensitivity (BRS). Seven types of recognized stressors were used to develop chronic stress rat model. Subcutaneously implanting ALZET mini-osmotic pumps containing NPY were used to evaluate the action of NPY on the stressed male rats. We found that chronic stress showed no influence on baseline systolic blood pressure (SBP) and heart rate (HR), whereas NPY (85 μg for 30 days) could elevate baseline SBP and induce bradycardia in rats intervened by various stimuli. NPY pretreatment could preserve chronic stress-induced decreases in left ventricular systolic pressure (LVSP) and the maximum rate of change in left ventricular pressure in the isovolumic contraction period (+dp/dt(max)) but has shown no effect on left ventricular end diastolic pressure (LVEDP) and the maximum rate of change in left ventricular pressure in the isovolumic relaxation period (-dp/dt(max)). Notably, chronic stress led to baroreflex oversensitivity indicated by the elevated ratio of Δheart rate (HR)/ Δmean arterial blood pressure (MABP) in rats followed by vasoconstrictor (phenylephrine, PE) or vasodilator (sodium nitroprusside, SNP) administration, which was almost completely reversed by NPY pretreatment. The expressions of substance P (SP) and gamma aminobutyric acid A receptor (GABA(A)R) in nucleus tractus solitarius were increased in chronic stress rats, which were counteracted by NPY pretreatment. We conclude that chronic stress-induced baroreflex hypersensitivity could be blocked by NPY pretreatment. Furthermore, the altered expressions of neurotransmitters and receptors in the brainstem might contribute to this process.     

Impact of androgen-induced oxidative stress on hypertension in male SHR

Men have higher blood pressure than women, and androgens and oxidative stress have been implicated as playing roles in this sexual dimorphism. The spontaneously hypertensive rat (SHR) is an animal model of both androgen- and oxidative stress-mediated hypertension. Therefore, the present studies were performed to test the hypothesis that androgens cause hypertension in SHR in part by stimulating superoxide production via NADPH oxidase. Castration of male SHR reduced blood pressure by 15% and attenuated both basal and NADPH-stimulated superoxide production in kidney cortical homogenates. Expression of p47(phox) and gp91(phox) but not p22(phox) subunits of NADPH oxidase were significantly lower in kidney cortex from castrated males compared with intact males. Moreover, inhibition of NADPH oxidase with apocynin caused approximately 15 mmHg reduction in blood pressure and reduced basal and NADPH-stimulated superoxide production in intact male SHR, but had no effect on blood pressure or superoxide production in castrated males. These data support the hypothesis that androgens cause oxidative stress and thereby increase blood pressure in male SHR via an NADPH oxidase-dependent mechanism.     

Role of gastric microcirculation in the gastroprotection by glucocorticoids released during water-restraint stress in rats

Our previous investigations demonstrated that glucocorticoids released in response to stress protect gastric mucosa against stress-induced ulceration. This study was designed to determine whether gastric microcirculation is involved in the mechanism of gastroprotective glucocorticoid action. For this we evaluated the effects of deficiency of glucocorticoid production during 3 hr water-restraint stress and corticosterone replacement on the stress-induced gastric erosions, gastric microcirculation and arterial pressure in rats. The stress was produced in awake rats and gastric microcirculation and arterial pressure were evaluated in animals anesthetized in 3 hr after the onset of water-restraint stress. An in vivo microscopy technique for the direct visualization of gastric microcirculation was employed. The gastric submucosal and the superficial mucosal microvessels were monitored on television screen through a microscope and the pictures were stored by microfilming for the analysis of red blood cell velocity and vessel diameter. Gastric microcirculation was estimated on the base of both the volume blood flow velocity in submucosal microvessels and the diameter of superficial mucosal venous microvessels. Gastric erosions were quantitated by measuring the area of damage. Plasma corticosterone levels were also measured after 3 hr stress by fluorometry. Water-restraint stress induced an increase in corticosterone level, an appearance of gastric erosions, a decrease in volume blood flow velocity of submucosal microvessels, a dilatation of superficial mucosal microvessels, a decrease in arterial pressure. The deficiency of glucocorticoid production during water-restraint stress promoted the stress-induced gastric ulceration, a dilatation of mucosal microvessels, a decrease of blood flow velocity in submucosal microvessels and of arterial pressure. Corticosterone replacement eliminated the effects of deficiency of glucocorticoid production on all of the parameters under study. Thus, the stress-induced corticosterone rise decreased gastric ulceration, restricted both the reduction of blood flow velocity in submucosal microvessels and a dilatation of superficial mucosal venous microvessels during water-restraint stress. These data suggest that the gastroprotective action of glucocorticoids during stress may be provided by the maintenance of gastric blood flow.     

肠道菌群在应激诱发大鼠高血压中的作用

观察应激性高血压大鼠肠道菌群的变化,探索肠道菌群在应激性高血压发生中的作用。应激性高血压模型的制备:大鼠每天2次接受足底电刺激加噪声的应激,每次2 h,中间间隔4 h,共14 d。血压的测量:大鼠股动脉插管,Powerlab系统记录血压。伪无菌鼠的制备:在大鼠的饮用水中加入氨苄西林(1 g/L)、万古霉素(500 mg/L)、新霉素(1 g/L)和甲硝唑(1 g/L)4种抗生素,共持续4周。采用Illumina MiSeq测序技术,测定大鼠粪便中微生物16S rRNA V3-V4区序列,并对群落结构和多样性进行比较分析。慢性应激导致大鼠血压升高,心率加快,血清去甲肾上腺素浓度增加;α多样性分析显示应激大鼠肠道菌群丰富度和多样性下降,β多样性分析显示应激组大鼠肠道菌群物种组成变少,差异性变大;伪无菌鼠的肠道菌群物种单一,仅有少量的变形菌门。给予伪无菌鼠相同的慢性应激,不能引起大鼠血压升高、心率增快,血清去甲肾上腺素浓度未升高。应激引起大鼠肠道菌群紊乱,应激性高血压的发生可能依赖于肠道菌群的状态。     

Sex differences in the cholinergic status of white rats]

Female rats injected with organophosphate inhibitor of acetylcholinesterase chlorophose at doses of 10 mg/kg and 360 mg/kg showed less considerable decrease in blood acetylcholinesterase activity than did male animals. Females compared with males also demonstrated less expressed clinical symptoms of poisoning (salivation, convulsion) after injection of chlorophose at dose of 360 mg/kg. The value of LD50 in female rats was 860 mg/kg, whereas the comparable value in male animals was 700 mg/kg. Following the injection of atropine at doses of 0.1, 0.3, 0.6 mg/100 g female rats showed 2-3 fold increases in basal adrenal and plasma corticosterone levels, but significant decreases in stress-induced corticosterone levels. As for males, the basal and stress-induced values of corticosterone were not significantly affected by atropine administration. These results suggest that functional reserves of cholinergic system and responsiveness of the hypothalamic-pituitary-adrenal axis to cholinergic influence are greater in females than in males. It is concluded that cholinergic status is significantly higher in female rats than in male ones.     

Influence of vasoactive intestinal polypeptide (VIP) on splanchnic and central hemodynamics in healthy subjects

The influence of VIP, a potent vasodilator, on central hemodynamics, splanchnic blood flow and glucose metabolism was studied in six healthy subjects. Teflon catheters were inserted into an artery, a femoral vein and a right-sided hepatic vein. A Swan-Ganz catheter was introduced percutaneously and its tip placed in the pulmonary artery. Determinations of cardiac output, systemic, pulmonary arterial and hepatic venous pressures as well as splanchnic blood flow were made in the basal state and at the end of two consecutive 45 min periods of VIP infusion at 5 and 10 ng/kg/min, respectively. Arterial blood samples for analysis of glucose, FFA, insulin and glucagon were drawn at timed intervals. VIP infusion at 5 ng/kg/min resulted in an increase in cardiac output (55%) and heart rate (25%) as well as a reduction in mean systemic arterial pressure (15%) and vascular resistance (45%). With the higher rate of VIP infusion heart rate tended to rise further while cardiac output and arterial pressure remained unchanged. At 15 min after the end of VIP infusion the above variables had returned to basal levels. Splanchnic blood flow and free hepatic venous pressure did not change significantly. Arterial concentrations of glucose, FFA, insulin and glucagon increased during VIP infusion. At 15 min after the end of infusion the glucose levels were still significantly higher than basal (20%). Net splanchnic glucose output did not change in response to VIP infusion. It is concluded that VIP exerts a potent vasodilatory effect resulting in augmented cardiac output and lowered systemic blood pressure and vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Catecholamine Release and Excretion in Rats with Immunologically Induced Preganglionic Sympathectomy

Abstract: Plasma and urinary catecholamines were quantified to assess global sympathoadrenal function in rats with preganglionic lesions caused by antibodies to acetyl-cholinesterase (AChE). Rats were given intravenous injections of normal mouse IgG or murine monoclonal anti-acetylcholinesterase IgG (1.5 mg). Five or 16 days afterward, basal blood samples were taken through indwelling arterial cannulae. A few hours later, the rats were immobilized for 10 min in padded restrainers, and another blood sample was drawn. HPLC determinations showed low basal levels of norepinephrine and epinephrine (<0.2 ng/ml in all rat plasma samples). In control rats, immobilization stress increased levels of plasma catecholamines up to 35-fold. In rats tested 5 days after injection of antibody, the norepinephrine response was much smaller (15% of control), and (he epinephrine response was nearly abolished (5% of control). There was some recovery at 16 days after antibody treatment, but stress-induced catecholamine release was still markedly impaired. Reduced stress-induced release: was not accompanied by major changes in tissue epinephrine or norepinephrine (heart, spleen, adrenal glands, and brain), although adrenal dopamine content dropped by 60%. Urinary excretion was studied in parallel experiments to gain insight into the effects of AChE anti-bodies on basal sympathoadrenal activity. Epinephrine, norepinephrine, dopamine, and selected metabolites were quantified in 24-h urine samples collected at frequent intervals for 30 days after antibody injection. No statistically gnificant changes were detected in the urinary output of dopamine, 3-methoxytyramine, normetanephrine, or 3-methoixy-4-hydroxyphenylglycol. On the other hand, epinephrine and norepinephrine output increased sharply at the time of antibody injection and then fell significantly below control levels. Norepinephrine output returned to normal after 2 weeks, but epinephrine output remained depressed. These results are consistent with previous evidence of widespread and persistent antibody-mediated βmade to the preganglionic sympathetic system.     

Specific components of face perception in the human fusiform gyrus studied by tomographic estimates of magnetoencephalographic signals: a tool for the evaluation of non-verbal communication in psychosomatic paradigms

Background  

In some hypertensive patients, psychological stress makes blood pressure difficult to control and causes physical symptoms such as headache or dizziness. We report the case of a hypertensive man whose psychological stress-induced increase in blood pressure was attenuated by cilnidipine.     

Effects of naloxone on basal and stress-induced prolactin secretion,in intact,hypothalamic deafferentated,adrenalectomized, and dexamethasone-pretreated male rats

The effects of naloxone (Nal) on basal and stress-induced PRL secretion were investigated in intact (N) adult male rats, as were its effects in rats with complete hypothalamic deafferentiation (CHD), in adrenalectomized (adrenX) rats, and in rats pretreated with dexamethasone (dex). Forty-five minutes subsequent to Nal administration (5mg/kg, BW, IP) basal serum levels of PRL were reduced by approximately 25% (p<0.05), in both N and CHD groups. PRL secretory responses to acute exposure to both photic and acoustic stress were markedly attenuated in Nal-injected, as compared to vehicle-injected animals. Basal serum PRL concentrations were elevated by 40% in adrenX rats (p<0.05), as compared to controls. In (p<0.05) in dex-treated rats, as compared to controls. In both these experimental groups, Nal administration caused significant reductions in serum PRL. This study demonstrates that stress-induced, as well as basal PRL secretion, is attenuated by Nal, and points to a hypothalamic site of action in this regard. Furthermore, these Nal effects are independent of glucocorticoid interactions with the CNS.