Morphofunctional characteristics of adrenal reactivity in rats of different ages

Ultrastructural peculiarities of the cortical and medullary substance of the adrenals have been studied in mature (8-month-old) and old (26-month-old) intact white male rats and in rats of the same age groups in 3 h after electrical stimulation of the hypothalamic ventromedial nuclei. By means of certain biochemical methods contents of hormones (corticosterone, adrenaline and noradrenaline) have been estimated, as well as that of cholesterin and ascorbic acid in blood and adrenal tissues. After the hypothalamus is stimulated in the mature rats, certain peculiarities in the adrenals reactivity are revealed; they demonstrate positive ultrastructural and functional correlation of secretory cells in the cortex and medulla and are characterized with hypertrophy of the nuclei, increased amount of polyribosomes, hypertrophied Golgi complex and canaliculi of the endoplasmic reticulum and increased contents of corticosteroids and catecholamines in blood. In the old rats after stimulation of the hypothalamus, certain unequal ultrastructural and functional peculiarities are revealed. They demonstrate both disturbance of the hypothalamic regulation of the adrenal function at ageing and decreased adaptive possibilities of the adrenal secretory cells at the subcellular level.     

Platelet antiaggregatory substances inhibit arachidonic acid induced coronary constriction

Isolated perfused hearts of rats and guinea pigs reacted to arachidonic acid (AA) with coronary vasoconstriction followed by vasodilatation. The infusion of prostacyclin (PGI2), Iloprost, hydralazine (HYD), and nifedipine (NFP) elicited a vasodilatation that nullified the coronary flow reserve, therefore the AA-induced vasodilatation was abolished. Dipyridamole (DPY) and 1-methyl-3-isobutylxanthine (MIX) produced a slight coronary dilatation without restricting the dilatation induced by AA. Regardless of their vasodilator action, all these drugs acted by inhibiting the AA-induced coronary constriction, while their infusion lasted. We postulated that a thromboxane-like substance, formed from AA in the vascular walls, would be responsible for the coronary vasoconstriction caused by AA. The inhibition of the AA-induced coronary constriction by PGI2, Iloprost, HYD, NFP, DPY, and MIX may be explained by an inhibitory action of these drugs on the synthetic processes of the thromboxane-like substance.     

α-Phenyl N-Tert-Butyl Nitrone (PBN) Increases the Cortical Cerebral Blood Flow by Inhibiting the Breakdown of Nitric Oxide in Anesthetized Rats

The effects of intravenous administration of a-phenyl N-tert-butyl nitrone (PBN) on cortical cerebral blood flow (CBF) were examined in Wistar rats under pentobarbital anesthesia and artificial ventilation. The cortical CBF in parietal cortex was measured by laser Doppler flowmetry. Intravenous administrations of 2 mg/kg and 20 mg/kg of PBN dose-dependently produced significant increases in cortical CBF and decreases in systemic blood pressure (BP). To examine whether these increased responses in cortical CBF produced by PBN were associated with the vasodilatation system of nitric oxide (NO), the NO synthase inhibitor L-N^G-nitroarginine (L-NOArg), which is an analog of L-arginine, was used to inhibit the NO-related-vasodilatative system. Since the PBN-induced responses in the cortical CBF were much attenuated in L-NOArg-treated rats (30 mg/kg, iv.), it was inferred that NO-related vasodilatation was strongly associated with the PBN-induced increase in cortical CBF.     

Sympathetic innervation of the splanchnic region mediates the beneficial hemodynamic effects of 8-OH-DPAT in hemorrhagic shock

Administration of the 5-HT(1A) receptor agonist, 8-OH-DPAT, improves cardiovascular hemodynamics and tissue oxygenation in conscious rats subjected to hypovolemic shock. This effect is mediated by sympathetic-dependent increases in venous tone. To determine the role of splanchnic nerves in this response, effects of 8-OH-DPAT (30 nmol/kg iv) were measured following fixed-arterial blood pressure hemorrhagic shock (i.e., maintenance of 50 mmHg arterial pressure for 25 min) in rats subjected to bilateral splanchnic nerve denervation (SD). Splanchnic denervation decreased baseline venous tone as measured by mean circulatory filling pressure (MCFP) and accelerated the onset of hypotension during blood loss. Splanchnic denervation did not affect the immediate pressor effect of 8-OH-DPAT but did reverse the drug's lasting pressor effect, as well as its ability to increase MCFP and improve metabolic acidosis. Like SD, adrenal demedullation (ADMX) lowered baseline MCFP and accelerated the hypotensive response to blood withdrawal but also reduced the volume of blood withdrawal required to maintain arterial blood pressure at 50 mmHg. 8-OH-DPAT raised MCFP early after administration in ADMX rats, but the response did not persist throughout the posthemorrhage period. In a fixed-volume hemorrhage model, 8-OH-DPAT continued to raise blood pressure in ADMX rats. However, it produced only a transient and variable rise in MCFP compared with sham-operated animals. The data indicate that 8-OH-DPAT increases venoconstriction and improves acid-base balance in hypovolemic rats through activation of splanchnic nerves. This effect is due, in part, to activation of the adrenal medulla.     

Continuous Detection of Cerebral Vasodilatation and Vasoconstriction Using Intracranial Pulse Morphological Template Matching

Although accurate and continuous assessment of cerebral vasculature status is highly desirable for managing cerebral vascular diseases, no such method exists for current clinical practice. The present work introduces a novel method for real-time detection of cerebral vasodilatation and vasoconstriction using pulse morphological template matching. Templates consisting of morphological metrics of cerebral blood flow velocity (CBFV) pulse, measured at middle cerebral artery using Transcranial Doppler, are obtained by applying a morphological clustering and analysis of intracranial pulse algorithm to the data collected during induced vasodilatation and vasoconstriction in a controlled setting. These templates were then employed to define a vasodilatation index (VDI) and a vasoconstriction index (VCI) for any inquiry data segment as the percentage of the metrics demonstrating a trend consistent with those obtained from the training dataset. The validation of the proposed method on a dataset of CBFV signals of 27 healthy subjects, collected with a similar protocol as that of training dataset, during hyperventilation (and CO₂ rebreathing tests) shows a sensitivity of 92% (and 82%) for detection of vasodilatation (and vasoconstriction) and the specificity of 90% (and 92%), respectively. Moreover, the proposed method of detection of vasodilatation (vasoconstriction) is capable of rejecting all the cases associated with vasoconstriction (vasodilatation) and outperforms other two conventional techniques by at least 7% for vasodilatation and 19% for vasoconstriction.     

H1 and H2 histamine actions on lung vessels; their relevance to hypoxic vasoconstriction.

Pulmonary vasomotor actions of histamine and the possible relationship of histamine to hypoxic pulmonary vasconstriction were studied in anaesthetized cats with one lobe of lung perfused at constant flow and in isolated perfused rat and ferret lungs. In the cat histamine caused dilatation, biphasic responses and constriction with increasing doses. Histamine induced dilatation was better demonstrated during hypoxic vasoconstriction and was reduced by an H2 histamine antagonist; constriction with histamine was abolished by an H1 antagonist. Histamine also caused both vasodilatation and vasoconstriction in ferret lungs. A mast cell stabilizing agent had no effect on hypoxic pulmonary vasoconstriction in cats or rats. This response was unaffected in cats but greatly reduced in rats and ferrets by cyproheptadine, a combined histamine and 5-hydroxy-tryptamine inhibitor. It was unaffected in cats but abolished in ferrets an H1 histamine inhibitor. It was again unaffected in cats but greatly reduced in rats and ferrets by an H2 histamine inhibitor. These species differences may reflect differences in mechanism but more probably reflect non-specific effects of the inhibitors in certain circumstances. However, when drugs nearly abolished hypoxic vasoconstriction, ATP still caused vasoconstriction.     

Adrenal function of rats in hypokinesia

Histological and biochemical examinations of the adrenals and plasma of rats for 3 months exposed to hypokinesia have shown that low motor activity led to a decrease in blood corticosterone level in spite of adrenal cortex hypertrophy. The decreased corticosterone blood level was not indicative of adrenal exhaustion, as the adrenals produced a greater amount of corticosterone in response to additional stress stimulus (5-hour immobilisation of animals in an extended state), as compared to the control. The increased production of corticosterone in response to stress stimulus caused no structural transformations or delipoidization of the cortical substance. This indicated that the reserve potentials of the adrenals increased with the animal adaptation to hypokinesia. The major morphological indication of higher adrenal functional activity in hypokinetic animals was an enhanced destruction of lymphocytes in the thymus cortex, the target organ for corticosteroids produced by the adrenals in response to an additional stress stimulus.     

Morphofunctional reorganization of the kidneys in lymphatic outflow disturbance

In 115 Wistar male rats structures and rates of tissue blood flow have been studied in the cortical and medullary renal substance histologically, polarographically (estimation of the volumetric tissue blood flow by hydrogen clearance). Systemic arterial (peritoneal aorta), venous (caudal vena cava) and lymphatic (renal lymph nodes) pressures have been measured, normal and after ligation of the thoracic duct at early (1-3 days), middle (1 month) and late (2-3 months) periods. In 1-3 days edema and dystrophy of the renal parenchyma, decrease of the blood flow rate in the cortical and its increase in the renal medullary substance, as well as a sharp elevation of pressure in the lymph nodes are observed. In 1 month of the experiment together with dystrophy and edema moderate sclerosis, decreasing blood flow rate in the cortical and medullary substance are noted. Increase of the systemic arterial and venous pressure and decreasing pressure in the lymph nodes, as well as a sharp increase of the renal nodes mass are revealed. In 2-3 months of the experiment, together with sclerosis of the renal parenchyma, elevated blood flow rate is observed in the kidneys and decreasing pressure in the lymph nodes up to its initial value takes place.     

The influence of age on the activity of the renin-angiotensin system in rats with adrenal-regeneration hypertension

In female rats aged 21 and 80 days, uninephroadrenalectomy with enucleation of the remaining adrenal was performed and 0.17 mol X l-1 saline offered as the only drinking fluid. The changes of plasma concentration of renin (PRC), and its substrate (RSC) and renal renin activity (RRA), considered as an indicator of the secretory activity of the regenerating adrenal were studied 5, 10, 20, 40 and 60 days after the adrenal enucleation to look for possible age differences related to the higher susceptibility of immature rats to the hypertensive influence of the regenerating adrenal. It has been found that: 1. In adrenal-enucleated rats the saline-induced decrease of RRA was delayed for a shorter time period in immature rats than in adult ones (5 vs. 10 days), during which blood pressure, saline consumption and RSC were lowered. The decrease of PRC was retarded in the older group only. 2. In rats with regenerating adrenals the PRC and RRA decrease was greater in animals subjected to enucleation of the remaining adrenal gland when immature, than in those operated when adult. At the end of the experiment this age difference disappeared. 3. The age difference in PRC and RRA suppression appeared during the period, when neither blood pressure nor saline consumption were higher in immature rats than in adult ones. 4. In rats with regenerating adrenals the renal mass was greater than in saline drinking controls. In the younger group, which in contrast to the adult one developed hypertension, this increase was greater and directly related to the blood pressure level from the 20th post-enucleation day onwards. It is being suggested that the changes of PRC, RRA and RSC observed up to the 10th post-enucleation day indicates relative adrenal insufficiency, the shorter duration of which in immature rats reflects their higher sensitivity to mineralocorticoids produced by the regenerating adrenal. This also manifests itself by greater PRC and RRA suppression in this age group. The haemodynamic results of the greater RRA suppression in the not yet fully developed kidneys of immature rats may facilitate the development of a "vicious circle" mechanism between blood pressure and hypertensive renal damage and thus contribute to the higher sensitivity to adrenal-regeneration hypertension.     

Circulatory regulation in anuric rats: anuria and haemorrhagic hypotension.

In rats made anuric by ureteral ligation or by creating a bladder-caval venous shunt, cardiac index increased and total peripheral resistance decreased proportionally to the change in the serum NPN level. Circulating blood and plasma volume did not change. In ureteral-ligated or bladder-caval venous-shunted rats, cardiac output and its organ fractions were determined by SAPIRSTEIN'S technique. In the ureteral-ligated animals, vasoconstriction in the kidneys, and vasodilation in the skin were found. After bladder-caval shunt, vasodilatation developed in the myocardium, gut, skin and carcass. After ureteral ligation, posthaemorrhagic shifting decreased mainly the renal flow, while after a bladder-caval venous shunt, mainly the renal and intestinal flows.     

Effect of alterations in ambient temperature on blood flow in the skin.

The effect of changing ambient temperature on skin temperature was recorded in human subjects; also, its effect on blood flow was measured using venous occlusion and optical plethysmography. When cold stimulus was removed in stages using a heating cabinet, it was found that a biphasic flow response occurred in the fingers with each step change in temperature. There was a rapid transient rise followed by a decline to an equilibrium flow level. The transient rise occurred even when the temperature rose from 37 to 40 degrees C, although at this level the equilibrium remained unchanged. It is suggested that the transient rise was due to stimulation of Hensel's dynamic warmth receptors, whereas the rise in equilibrium temperature was due to removal of cold stimulus, which at low ambient temperatures maintains reflex vasoconstriction through activation of static cold receptors. Upper arm skin responded to removal of cold stimulus by a fall in temperature. Immersion of a different limb in cold water produced vasoconstriction in fingers but vasodilatation in the upper arm skin. It is suggested that this may be due to neurogenic vasodilatation, though the present work gives no indication as to pathways.     

Habituation of vasodilatation in the calf elicited by repeated sensory stimulation in man

In 28 subjects the cardiovascular response to repeated stimulation was monitored during six daily sessions. Calf blood flow was measured with mercury-in-silastic venous occlusion plethysmography, blood pressure with electronic sphygmomanometer. The stimuli used were: 1 kHz sound of 90 dB and 100 dB intensity and immersion of one foot for 60 s in water at 4 degrees C. Initially sounds induced large vasodilatation in the calf, immersion of one foot in the water induced in the contralateral calf vasodilatation in one group and vasoconstriction in another group of subjects. The blood pressure changes were less prominent and less consistent. After the first session of repeated stimulation the vascular response during the second session was significantly diminished. The reduction of the vasodilatation was the most rapid. During the remaining 5 days the responses were suppressed. It has been established that in the patients in the initial stage of hypertension the ability to habituate vascular response is impaired (Zbrozyna and Krebbel 1985). It is therefore suggested that the test of the ability for long-term vascular habituation could be used as a supplementary diagnostic test.     

Changes in the argyrophil carcass of the lobules of the thymus gland during its age-related involution

Fibrillar components of the thymus lobules have been studied in persons 9-73 years of age and in 11-30 month-old noninbred white rats. Beginning from 9-10 years of age, i. e. before the onset of age involution, in the medullary substance of the lobules argyrophil carcass is formed; it includes numerous microvessels. At the age of 30-40 years a part of argyrophil fibers is subjected to destruction. At the same time in the medullary substance adipocytes appear. Their increasing amount is accompanied with substitution of the medullary substance for adipose substance, while a part of the cortical substance is preserved. These data are confirmed, when the thymus in old animals is studied. Ultrastructural manifestations of extra- and intracellular destruction of fibers are noted in them, too. The dynamics of the fibrillar component changes in the thymus in different animal individuals is not the same and can serve as one of the criteria of its age involution.     

Biphasic actions of angiotensin IV on renal blood flow in the rat

Our aim was to investigate the changes in renal blood flow during brief exposure of the renal vasculature to angiotensin IV (Ang IV). Total renal blood flow was measured by electromagnetic flowmetry in pentobarbital-anesthetized male Sprague Dawley rats. Intrarenal injection of Ang I, Ang II and Ang III produced a dose-dependent vasoconstriction. In contrast, Ang IV and Ang-(3-10) produced a dose-dependent rapid vasoconstriction (lasting seconds) followed by a transient vasodilatation (lasting minutes). The biphasic response to Ang IV was unchanged in rats pre-treated with captopril, whereas the Ang-(3-10) response was abolished implying that its vasoactive activity was due to the generation of Ang IV. The vasodilatory component of Ang IV was unaffected by indomethacin. The biphasic vasoactive response of Ang IV was unaffected by divalinal-Ang IV (AT(4) receptor antagonist) or PD 123319 (AT(2) receptor antagonist), but greatly reduced by losartan or L-158,809 (AT(1) receptor antagonists). These results suggest that Ang IV is distinct from other angiotensins in that it possesses non-prostaglandin mediated renal vasodilatory activity that is apparently linked to the renal vascular AT(1) receptor.     

Effect of chlorphentermine on hormone content and function of the adrenal cortex in rats.

Amphiphilic drugs like chlorphentermine induce a generalized lipid storage disease upon chronic application. The adrenal cortex is among the organs most heavily affected. We therefore determined the urinary corticosterone excretion during the treatment of rats with chlorphentermine and the corticosterone content of the adrenals and its blood level at the end of the treatment period. In addition, the responsiveness of adrenal cortex was tested by application of ACTH. During treatment, the corticosterone excretion declined considerably. Both the corticosterone content of the adrenals and the plasma level were found depressed at the end of a treatment period of 8 weeks. The ACTH evoked response was also diminished. The results indicate that the chlorphentermine-induced lipidosis is associated with a reduced corticosterone production of the adrenal cortex of rats. At present it cannot be decided whether the cortical insufficiency is causally related to lipidotic alterations of the cortical cells, or whether it is caused or additionally influenced by alteration at a higher level, e.g. hypothalamic centers or anterior pituitary.     

Chronic hypoxia attenuates nitric oxide-dependent hemodynamic responses to acute hypoxia

Alterations in the nitric oxide (NO) pathway have been implicated in the pathogenesis of chronic hypoxia-induced pulmonary hypertension. Chronic hypoxia can either suppress the NO pathway, causing pulmonary hypertension, or increase NO release in order to counteract elevated pulmonary arterial pressure. We determined the effect of NO synthase inhibitor on hemodynamic responses to acute hypoxia (10% O(2)) in anesthetized rats following chronic exposure to hypobaric hypoxia (0.5 atm, air). In rats raised under normoxic conditions, acute hypoxia caused profound systemic hypotension and slight pulmonary hypertension without altering cardiac output. The total systemic vascular resistance (SVR) decreased by 41 +/- 5%, whereas the pulmonary vascular resistance (PVR) increased by 25 +/- 6% during acute hypoxia. Pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME; 25 mg/kg) attenuated systemic vasodilatation and enhanced pulmonary vasoconstriction. In rats with prior exposure to chronic hypobaric hypoxia, the baseline values of mean pulmonary and systemic arterial pressure were significantly higher than those in the normoxic group. Chronic hypoxia caused right ventricular hypertrophy, as evidenced by a greater weight ratio of the right ventricle to the left ventricle and the interventricular septum compared to the normoxic group (46 +/- 4 vs. 28 +/- 3%). In rats which were previously exposed to chronic hypoxia (half room air for 15 days), acute hypoxia reduced SVR by 14 +/- 6% and increased PVR by 17 +/- 4%. Pretreatment with L-NAME further inhibited the systemic vasodilatation effect of acute hypoxia, but did not enhance pulmonary vasoconstriction. Our results suggest that the release of NO counteracts pulmonary vasoconstriction but lowers systemic vasodilatation on exposure to acute hypoxia, and these responses are attenuated following adaptation to chronic hypoxia.     

Species differences in the reflex effects of lingual afferent nerve stimulation on lip blood flow and arterial pressure

We evoked changes in lower lip blood flow and systemic arterial blood pressure by electrically stimulating the central cut end of the lingual nerve in artificially ventilated, urethane-anesthetized, cervically vago-sympathectomized cats, rats, rabbits, and guinea pig. The systemic arterial blood pressure changes were species-dependent: increases in rat, consistent decreases in rabbit and guinea pig, and variable among individuals in cat. In cat and rabbit, lip blood flow increases, which occurred only ipsilaterally to the stimulated nerve and showed no statistically significant correlation with the systemic arterial blood pressure changes. In rat, the ipsilateral lip blood flow increase was markedly greater than the contralateral one, and although there was a significant correlation between each of them and the systemic arterial blood pressure changes, the ipsilateral increase presumably included an active vasodilatation. In guinea pig, lip blood flow decreased on both sides in proportion to the systemic arterial blood pressure reductions. Thus, species variability exists in the sympathetic-mediated systemic arterial blood pressure changes and parasympathetic-mediated lip blood flow responses themselves, and in the relationship between them.Abbreviations a.u. arbitary units - LBF lip blood flow - LN lingual nerve - SABP systemic arterial blood pressure - SP substance P - Vsp trigeminal spinal nucleusCommunicated by I.D. Hume     

CGRP和NPY 在大鼠股骨闭合骨折愈合不同阶段的变化及意义

目的:探讨交感神经分泌的神经肽Y(NPY)和感觉神经分泌的钙基因相关肽(CGRP)在体内骨折愈合的不同阶段的变化及意义。方法:选择6-8月龄的雄性大鼠,建立大鼠的股骨闭合骨折模型,术后2、4、8、12周取材。进行扫描电镜,免疫组织荧光染色和血清Elisa检测。结果:1骨折愈合不同时期感觉神经肽类物质CGRP和交感神经肽类物质NPY都有表达,且其含量有先增加后减少的趋势,并在骨折后8周含量达到最高。2骨折愈合不同阶段的大鼠血清感觉神经肽类物质CGRP和交感神经肽类物质NPY均呈上升趋势,差异有统计学意义(P0.05),且NPY的含量比CGRP的含量高。骨折后2-4周,CGRP含量增加较快;骨折后4-8周NPY含量增加较快。结论:骨折愈合的不同阶段,感觉神经肽类物质CGRP和交感神经肽类物质NPY含量先升后降,对不同阶段的骨形成及骨吸收产生影响。     

Human recombinant erythropoietin alters the flow-dependent vasodilatation of in vitro perfused rat mesenteric arteries with unbalanced endothelial endothelin-1 / nitric oxide ratio

Chronic use of human recombinant erythropoietin (r-HuEPO) is accompanied by serious vascular side effects related to the rise in blood viscosity and shear stress. We investigated the direct effects of r-HuEPO on endothelium and nitric oxide (NO)-dependent vasodilatation induced by shear stress of cannulated and pressurized rat mesenteric resistance arteries. Intravascular flow was increased in the presence or absence of the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME; 10(-4) mol/L). In the presence of r-HuEPO, the flow-dependent vasodilatation was attenuated, while L-NAME completely inhibited it. The association of r-HuEPO and L-NAME caused a vasoconstriction in response to the rise in intravascular flow. Bosentan (10(-5) mol/L), an inhibitor of endothelin-1 (ET-1) receptors, corrected the attenuated vasodilatation observed with r-HuEPO and inhibited the vasoconstriction induced by flow in the presence of r-HuEPO and L-NAME. r-HuEPO and L-NAME exacerbated ET-1 vasoconstriction. At shear stress values of 2 and 14 dyn/cm(2) (1 dyn = 10(-5) N), cultured EA.hy926 endothelial cells incubated with r-HuEPO, L-NAME, or both released greater ET-1 than untreated cells. In conclusion, r-HuEPO diminishes flow-induced vasodilatation. This inhibitory effect seems to implicate ET-1 release. NO withdrawal exacerbates the vascular effects of ET-1 in the presence of r-HuEPO. These findings support the importance of a balanced endothelial ET-1:NO ratio to avoid the vasopressor effects of r-HuEPO.     

Effect of arterial hypoxia on the cerebrocortical redox state, vascular volume, oxygen tension, electrical activity and potassium ion concentration.

The effect of different degrees of arterial hypoxia on cerebrocortical NAD/NADH redox state, reflectance, oxygen tension, extracellular potassium ion concentration, ECoG and arterial blood pressure was investigated in rats. The results may be summarized as follows. a) The decrease of cortical pO2 preceded the dilatation of cortical vessels by 15-20 sec but the changes in cortical extracellular potassium ion concentration, ECoG and arterial blood pressure started later than the vasodilatation. These results give further support to the regulatory role of cortical pO2 decrease in the initiation of cerebrocortical vasodilatation during arterial hypoxia. b) Since the K+ concentration of the brain cortex and the ECoG did not change in mild arterial hypoxia, the significant NAD reduction obtained in this experimental group is likely to be of cytoplasmic origin. The same conclusion applies to the initial periods of severe arterial hypoxia. On the basis of the extent of NAD reduction during various degrees of arterial hypoxia it is concluded that about 30% of the NAD reduction occurring in anoxia is of cytoplasmic origin. c) When the animals were ventilated with a gas mixture containing 4-7% oxygen, the brain cortex became nearly anoxic, partly because of the gradual decrease of arterial blood pressure. Finally, the mechanism of potassium leakage is identical under prolonged severe arterial hypoxaemia and on anoxic terminal depolarization.