Effect of beta adrenergic receptor stimulation on integrated systemic venous bed

Summary In 28 mongrel dogs, venous return was completely drained from the caval veins, led to an oxygenator and returned to the femoral arteries with a pump. Blood pressures in both caval veins and perfusion rate were kept constant. Changes in the oxygenator weight were recorded and reflected changes in systemic venous blood volume.Isoproterenol and epinephrine (2–8 g/kg) decreased systemic venous blood volume by up to 5 ml/kg. After denervation of arterial pressoreceptors, isoproterenol had a smaller and epinephrine a larger effect. After beta receptor blockade with prindolol (300–600 g/kg), isoproterenol had no effect, whereas the epinephrine effect was smaller. After alpha receptor blockade with phentolamin (2500 g/kg), epinephrine slightly decreased venous blood volume. Prindolol, administered alone, increased venous volume by 3 ml/kg.It is concluded that the systemic venous bed contains both alpha and beta receptors, and that stimulation of both receptor sites effects predominantly a venoconstriction which must result in an increase in venous return and in cardiac output. This effect should be considered, when beta receptor blocking agents are used in antianginal and antihypertensive treatment.     

The role of the splanchnic circulation in the regulation of total intravascular volume during alpha adrenergic receptor stimulation

Previous studies have not defined the contribution of the splanchnic circulation to the total intravascular volume change associated with selective alpha adrenergic receptor stimulation. Since the splanchnic circulation is responsible for the total volume changes associated with other types of selective autonomic receptor stimulation, the present study was undertaken to examine the influence of alpha adrenergic receptor stimulation on splanchnic intravascular volume, the hemodynamic mechanism responsible for the splanchnic volume change, and the contribution of the splanchnic volume change to the change in total volume. In 35 anesthetized dogs, blood from the vena cavae was drained into an extracorporeal reservoir and returned to the right atrium at a constant rate so that changes in total intravascular volume could be measured as reciprocal changes in reservoir volume. Phenylephrine infusion (100 g/min) for 20 min in 28 dogs was associated with a decrease in total volume of 64±17 (SEM) ml (P<0.0001). The response was abolished by either alpha adrenergic blockade or evisceration but was not attenuated by beta adrenergic blockade, sinoaortic baroreceptor denervation, ganglionic blockade, or splenectomy. In 5 animals with separate splanchnic perfusion and drainage, total and splanchnic volumes decreased 59±8 ml (P<0.0001) and 317±20 ml (P<0.0001), respectively, while transhepatic vascular resistance increased 17±4 cm H₂O·min/l (P<0.0001). These responses were abolished after alpha adrenergic blockade. Thus, splanchnic volume decreases with alpha adrenergic receptor stimulation, despite an increase in hepatic resistance to splanchnic, venous outflow. The splanchnic volume decrement is entirely responsible for the total volume decrement.The study was supported by NHLBI Grant 1 R23-HL27185, Grant 11-203-812 from the American Heart Association of Greater Hartford, Inc., and the Duberg Cardiovascular Research Fund. Dr. Rutlen was the Duberg Scholar in Cardiovascular Disease when the study was performed.This work was presented in part at the 1982 Scientific Sessions of the American Heart Association (Circ. 66:II-311)     

α受体和儿茶酚胺所致心肌损害发生机理关系的实验研究

新西兰免78只分成8组。试验组、M组和对照组分别静滴去甲肾上腺素(NE)1毫克/公斤、美索克新明或生理盐水。其余5组在NE之前分别给予酚妥拉明(R组)、心得安(P组)、美多心安(MP组)、育亨宾(Y组)以及(口派)唑嗪(PR组)。以半定量方法分析心肌病理损害程度,并测定心肌中糖酵解中间产物11项以及能量代谢产物。结果发现NE组心肌损害显著(P<0.01);P组、MP组、Y组和M组心肌损害类似于NE组;R组和PR组则较NE组减轻(P<0.01)。NE组和MP组心肌尚有明显的代谢障碍,而R组则较接近正常。提示NE所致心肌损害中α受体,尤其α_1受体起了主要作用。作者等对其发生机理进行讨论,并提出新的假设。     

Supersensitivity of the renal tubule to catecholamines in the chronically denervated canine kidney

Experiments were performed on anesthetized dogs to study whether or not renal tubules of the chronically denervated kidney show supersensitivity toward circulating catecholamines. In one kidney the influence of plasma catecholamines was inhibited by intrarenal administration of the alpha adrenergic receptor blocker phenoxybenzamine (POB, 2 g/min), and renal parameters of the infused kidney were compared to those of the contralateral noninfused organ. Before POB infusion urine flow (V), urinary sodium and potassium excretion (U_NaV, U_KV) as well as clearance of inulin and PAH (GFR, C_PAH) were similar in infused and contralateral kidneys in all the groups studied. In dogs (n=8) with two innervated kidneys POB infusion elevated V and U_NaV by 53±13% and 102±34% (p<0.05). In dogs (n=8) with acute bilateral renal denervation POB administration failed to alter any of the measured parameters. In contrast, V and U_NaV from chronically denervated kidneys (n=7) were increased after POB infusion by 40±9% and 103±34% (p<0.05). Glomerular filtration rate, C_PAH and U_KV were not changed by alpha adrenoceptor blockade in any of the groups. In an additional group of animals (n=8) acute unilateral renal denervation increased V and U_NaV to a significantly higher extent (by 282±85% and 330±106%) than POB administration did in the innervated kidney and elevated U_KV (44±10%), too. It is concluded that supersensitivity to catecholamines developed in renal tubules of the chronically denervated dog kidney and, in consequence, circulating catecholamines at elevated plasma levels caused by surgery were capable of increasing tubular reabsorption of sodium and water.     

Ingestion in the satiated rat: role of alpha and beta receptors in mediating effects of hypothalamic adrenergic stimulation.

Anterior perifornical hypothalamic injection of l-norepinephrine in satiated rats elicits a brief, vigorous drinking response followed within a minute or two by a vigorous feeding response. These adrenergically elicited responses, which bear striking similarities to a rat's naturally motivated ingestive behaviors, were examined in the present series of experiments. It was found that: (1) Both responses could be elicited by perifornical hypothalamic injection of l-epinephrine, which was actually found to be more potent than l-norepinephrine. In contrast, only feeding could be elicited by the alpha-stimulant metaraminol, and neither feeding nor drinking could be elicited by hypothalamic injection of d-norepinephrine. l-isoproterenol, or dopamine. (2) The threshold doses of l-epinephrine for eliciting reliable ingestive responses were quite low, namely, 0.8 nmole (0.15 mug) for drinking and 0.2 nmole (0.04 mug) for feeding. (3) Pharmacological analysis of the ingestive behaviors induced by l-norepinephrine or l-epinephrine indicated that the eating response was mediated by alpha-adrenergic receptors, whereas the drinking response involved the synergistic action of both alpha- and beta-adrenergic receptors. No evidence for the involvement of dopaminergic or cholinergic (muscarinic) receptors was obtained. (4) A third adrenergically elicited phenomenon, namely, a suppression of drinking, was observed during and after the period of induced feeding. Analysis of this effect revealed its dependence solely upon alpha-adrenergic receptor activity.     

Yohimbine acts as a putative in vivo alpha2A/D-antagonist in the rat prefrontal cortex

Yohimbine has been widely used as alpha2-adrenergic receptor antagonist in neurophysiological research and in clinical therapy. In this study, we provide in vivo electrophysiological evidence, that microiontophoretic application of yohimbine (YOH) inhibits spontaneous activity of prefrontal neurons of the rat. By microiontophoretic application of the alpha2A-receptor antagonist BRL44408 (BRL), the effects of YOH could be mimicked, indicating that the action of YOH is manifested through alpha2A/D-receptor mechanisms. Furthermore, the inhibiting effects of YOH or BRL were blocked by alpha2B-receptor antagonist imiloxan. In concert with previous microiontophoretic data, the present findings suggest that alpha2-receptor antagonist YOH predominantly acts on the alpha2A/D-receptor subtype in vivo. Furthermore, we hypothesize that this action is manifested via deactivation of autoreceptors causing increased norepinephrine release, finally inhibiting postsynaptic neurons through the activation of alpha2B-receptors.     

Reduction in cortical beta adrenergic receptor density after chronic intermittent food deprivation

The effect of chronic intermittent food deprivation on beta adrenergic receptor binding in the rat brain was studied. Rats subjected to six 48 h fasts given over a period of 3 weeks demonstrated a reduction in the density of beta adrenergic receptors in the cerebral cortex but not in the hypothalamus or lower brainstem. This receptor alteration did not occur after one 48 h fast. This effect of chronic food deprivation is shared by several other forms of repeated stress, suggesting that it is a general mechanism of adaptation.     

Effects of different frequencies of transcutaneous electrical nerve stimulation on venous vascular reactivity

Transcutaneous electrical nerve stimulation (TENS) is a type of therapy used primarily for analgesia, but also presents changes in the cardiovascular system responses; its effects are dependent upon application parameters. Alterations to the cardiovascular system suggest that TENS may modify venous vascular response. The objective of this study was to evaluate the effects of TENS at different frequencies (10 and 100 Hz) on venous vascular reactivity in healthy subjects. Twenty-nine healthy male volunteers were randomized into three groups: placebo (n=10), low-frequency TENS (10 Hz, n=9) and high-frequency TENS (100 Hz, n=10). TENS was applied for 30 min in the nervous plexus trajectory from the superior member (from cervical to dorsal region of the fist) at low (10 Hz/200 μs) and high frequency (100 Hz/200 μs) with its intensity adjusted below the motor threshold and intensified every 5 min, intending to avoid accommodation. Venous vascular reactivity in response to phenylephrine, acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) was assessed by the dorsal hand vein technique. The phenylephrine effective dose to achieve 70% vasoconstriction was reduced 53% (P<0.01) using low-frequency TENS (10 Hz), while in high-frequency stimulation (100 Hz), a 47% increased dose was needed (P<0.01). The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) responses were not modified by TENS, which modifies venous responsiveness, and increases the low-frequency sensitivity of α1-adrenergic receptors and shows high-frequency opposite effects. These changes represent an important vascular effect caused by TENS with implications for hemodynamics, inflammation and analgesia.     

Role of specific adrenergic and cholinergic receptors of the blood vessel wall in the regulation of blood clotting during stimulation of the vagus nerve

Experiments on dogs showed that if the specific adrenergic receptors of the blood vessel wall (- and -receptors) were blocked by phentolamine or inderal it still continued to produce tissue blood clotting factors after stimulation of the vagus nerve. No response of this type was observed to stimulation of the nerve after the cholinergic receptors had been blocked by atropine. It is concluded that hyperfibrinolysis and hypercoagulation developing after vagus nerve stimulation are due to excitation of cholinergic structures.Department of Normal Physiology, Chita Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. N. Filatov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 78, No. 8, pp. 19–22, August, 1974.     

Effect of carbidine on adrenergic neurotransmission

Methods of physiological analysis were used to study the effect of the original psychotropic agent carbidine on adenergic neurotransmission on the isolated rat vas deferens as the model. The content of noradrenalin (NA) was determined spectrofluoremetrically in the same ducts and the ability of the neuroleptic to block the uptake of exogenous NA by the tissue also was investigated. Carbidine was found to possess an adrenomimetic effect, due to its ability to liberate NA, leading to a decrease in the endogenous reserves of the neuromediator.Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 79, No. 6, pp. 66–69, June, 1975.     

The effect of bed rest and an exercise countermeasure on leg venous function

This study was performed to assess the effect of resistive vibration exercise during bed rest deconditioning on venous vascular dimension and function, as measured with ultrasound in the popliteal vein. Sixteen men were assigned to bed rest (BR-Ctrl) or bed rest with resistive vibration exercise (BR-RVE). Before and at 25 and 52 days of bed rest, popliteal vein diameter was measured at increasing cuff pressures. Venous capacitance and compliance were calculated from the pressure–volume curve. After 52 days of bed rest, BR-Ctrl showed no change in baseline popliteal vein diameter or compliance, while venous capacitance decreased. Resistive vibration exercise had no effect on the response in venous diameter, capacitance or compliance to 52 days of bed rest. The decline in venous capacitance due to long-term bed rest is not effectively counteracted by resistive vibration exercise, indicating that an alternative factor during bed rest deconditioning is responsible for venous changes.     

Adrenergic control of bicarbonate absorption in the proximal convoluted tubule of the rat kidney

The effects of norepinephrine and phenoxybenzamine on bicarbonate absorption in the rat proximal convoluted tubule were studied by simultaneous microperfusion of tubule and peritubular capillaries. Bicarbonate was determined by using a pH-sensitive membrane electrode system. The rates of bicarbonate absorption were examined in the same proximal tubule before and after the addition of norepinephrine or phenoxybenzamine. When the proximal tubule was perfused with Ringer solution and peritubular capillaries were perfused with albumin Ringer solution, was 145±3.3 pEq/min×mm. Addition of 2×10^–6 mol/l norepinephrine to the capillary perfusate caused a 21% increase in . Addition of 2×10^–6 mol/l phenoxybenzamine to the capillary perfusate caused a 12% decrease in . Addition of both norepinephrine and phenoxybenzamine to the capillary perfusate caused a 19% decrease in . However, there was no significant effect on observed when either norepinephrine or phenoxybenzamine was added to the luminal perfusate. These results suggest that adrenergic nerves participate in the regulation of renal tubular bicarbonate absorption through the direct action of norepinephrine on adrenergic receptors located at the basolateral side of the proximal tubule.This work was supported by American Heart and Chicago Heart AssociationPart of this work was presented in Federation Meeting of American Societies for Experimental Biology and Medicine, Anaheim, California, April 1980     

Effects of prolonged high-altitude exposure on peripheral adrenergic receptors in young healthy volunteers

The regulation of adrenergic receptors during hypoxia is complex, and the results of published reports have not been consistent. In the present study blood cell adrenoceptor characteristics at sea level (SL) before and after prolonged exposure to high altitude (HA) were measured in seven trained young male lowlanders. Sympathoadrenal activity and clinical haemodynamic parameters were also evaluated before departure (SLB), after 1 week (HA1) and 4 weeks (HA4) at HA and 1 week after return to sea level (SLA). As compared to pre-departure sea level values, urinary norepinephrine excretion increased significantly during altitude exposure [SLB: 10.26 (3.04) μg · 3 h⁻¹; HA1: 23.2 (4.19) μg · 3 h⁻¹; HA4: 20.3 (8.68) μg · 3 h⁻¹] and fell to pre-ascent values 1 week after return to sea level [SLA: 9 (2.91) μg · 3 h⁻¹]. In contrast, mean urinary epinephrine levels did not increase over time at HA. Both systolic and diastolic blood pressures, as well as heart rate, were increased during HA exposure. The circadian blood pressure and heart rate rhythms were preserved during all phases of altitude exposure. Mean maximal binding (B _max) of the α₂-adrenoceptor antagonist [³H]rauwolscine to platelet membranes was significantly reduced (P < 0.001) after exposure to chronic hypoxia [SLB: 172.6 (48.5) fmol · mg⁻¹ protein versus SLA: 136.8 (56.1) fmol · mg⁻¹ protein] without change in the dissociation constant (K _D). Neither the lymphomonocyte β₂-adrenoceptor B _max [SLB: 38.5 (13.6) fmol · mg⁻¹ protein, versus SLA: 32.4 (12.1) fmol · mg⁻¹ protein] nor the K _D for [³H]dihydroalprenolol was affected by chronic hypoxia. Cyclic AMP (adenosine 3′,5′-cyclic monophoshate) generation in lymphomonocytes by maximal isoproterenol stimulation was not modified after prolonged HA exposure. In conclusion, the down-regulation of α₂-adrenoceptors appears to be an important component of the adrenergic system response to HA exposure. Accepted: 20 April 2000     

Effect of repetitive stimulation on the frog neuromuscular transmission

The elimination rate constant, half-life and turnover time of dopamine (DA) and norepinephrine (NE) were determined, after inhibiting their biosynthesis by -methyl-para-tyrosine (MT), in the hypothalamus, striatum and the remainder of the brain of rats exposed to different degrees of hypobaric hypoxia, corresponding to altitudes of 1,800, 3,800, 5,200 and 7,000 meters. The effects varied as a function of the degree of hypoxia and the brain region studied. The turnover time of NE in the hypothalamus remained unchanged, regardless of the altitude, while in the rest of the brain the rate constant of neurotransmitter elimination decreased inversely as a linear function of the degree of hypoxia. On the contrary, the changes of the DA turnover time in the striatum and the rest of the brain, were biphasic, being accelerated by moderate altitudes (1,800 m) and retarded by the two highest simulated altitudes studied as a function of hypoxia. The differential effects of hypoxia on NE and DA turnovers are attributed to different sensitivities of the respective enzyme systems.A preliminary report of this work was presented at the Fourth International Catecholamine Symposium, Pacific Grove, Sept. 1978     

Incorporation of acetate and phosphate into brain lipids during blocking of cholinergic and adrenergic receptors

Benactyzine (blocking M-cholinergic receptors) inhibits the incorporation of acetate and phosphate into brain lipids; haloperidol (blocking -adrenergic receptors) activates these processes. On this basis it is postulated that the conduction of the nervous impulse in cholinergic and adrenergic synapses of the brain is accompanied by changes in the intensity of lipid synthesis.(Presented by Academician of the Academy of Medical Sciences of the USSR, S. N. Golikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 78, No. 9, pp. 60–61, September, 1974.     

Sleep induction and temperature lowering by medial preoptic alpha(1) adrenergic receptors

Changes in sleep-wakefulness (S-W) and body temperature (T(b)) on administration of alpha(1) agonist (methoxamine) and antagonist (prazosin) into the medial preoptic area (mPOA) were studied in rats. Presynaptic catecholaminergic terminals of the mPOA were destroyed by injecting 6-hydroxydopamine at the ventral noradrenergic bundle (VNA), before administration of the drugs. Microinjection of 0.05 microg methoxamine induced sleep, though 0.1 microg prazosin produced no change in S-W. On the other hand, in normal rats, the same dose of methoxamine produced no change, while prazosin produced arousal. Denervation hypersensitivity may be responsible for the appearance of hypnogenic response on methoxamine administration, in the VNA-lesioned rats. The VNA-lesioned animals (before administration of any drug) had higher pre-injection values of wake period than the normal rats. A reduction in the tonic activity of noradrenergic fibers to the mPOA, and resulting reduced activity of alpha(1) receptors, may be responsible for increased wake period in the VNA-lesioned rats. The action of prazosin was probably abolished in the absence of tonic activity of alpha(1) receptor in the VNA-lesioned rats. Reduction and increase in T(b) produced by methoxamine and prazosin, respectively, confirm the involvement of alpha(1) receptors in the thermal changes. Methoxamine was less effective, than in normal rats, in reducing T(b). So, the possibility of involvement of presynaptic receptors in the thermal response is suggested. The results suggest the involvement of separate sets of alpha(1) receptors (and neurons) in hypnogenesis and in lowering T(b). As sleep is associated with fall in T(b), the alpha(1) adrenergic receptors may be involved in interlinking sleep regulation and thermoregulation.     

中国北方汉族人群β2肾上腺素能受体基因多态性研究

目的 :探讨 β2 AR16、2 7和 16 4位点基因多态性在中国北方汉族人群中的分布 ;方法 :采用等位基因特异性PCR方法 ,对 β2 AR基因多态性进行分析检测 ;结果 :中国汉族人群 β2 AR16位点基因多态性分布频率 :Arg/Arg基因型占 13% ,Arg/G1y基因型占 76 % ,G1y/G1y基因型占 11% ;β2 AR基因 2 7位点多态性分布频率 :G1n/G1n基因型占 36 % ,G1n/G1u基因型占5 5 % ,G1u/G1u基因型占 9% ;β2 AR基因 16 4位点多态性分布 ,Thr/Thr基因型占 30 % ,Thr/Ile基因型占 5 3% ,Ile/Ile基因型占17%。结论 :我国北方汉族人群存在 β2 AR基因多态性 ,其分布频率与英美高加索人群有一定差异     

Long-term enhanced desynchronization of the alpha rhythm following tetanic stimulation of human visual cortex

It had been shown previously that a photic tetanus induces LTP-like changes in the visual cortex, as indexed by an enhancement of the N1b component of the visual evoked potential, recorded non-invasively by electroencephalography. This potentiation was shown to last over 1 h. In the present study, the effect of a photic tetanus on oscillatory activity is investigated. EEGs were collected from eight healthy subjects in three conditions while visual checkerboards were displayed. Following baseline presentations in two conditions a lateralized visual tetanus was given, either to the left or right visual field, and in a third condition no tetanus was given. This was followed by a return to baseline presentations, both immediately after the tetanus/control block, and 1 h later. Enhanced event-related desynchronization (ERD) of the alpha rhythm lasting 1 h was seen following the photic tetanus over occipital electrodes. Because ERD of the alpha rhythm is thought to represent active cortex, these results suggest that the visual tetanus induces long-lasting cortical changes, with stronger neuronal assemblies and increased neuronal output.     

Calcitonin receptor-like receptor and receptor activity modifying protein 1 in the rat dorsal horn: localization in glutamatergic presynaptic terminals containing opioids and adrenergic alpha2C receptors

Calcitonin gene-related peptide (CGRP) is abundant in the central terminals of primary afferents. However, the function of CGRP receptors in the spinal cord remains unclear. CGRP receptors are heterodimers of calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1). We studied the localization of CRLR and RAMP1 in the rat dorsal horn using well-characterized antibodies against them, which labeled numerous puncta in laminae I-II. In addition, RAMP1 was found in cell bodies, forming patches at the cell surface. The CRLR- and RAMP1-immunoreactive puncta were further characterized using double and triple labeling. Colocalization was quantified in confocal stacks using Imaris software. CRLR did not colocalize with primary afferent markers, indicating that these puncta were not primary afferent terminals. CRLR- and RAMP1-immunoreactive puncta contained synaptophysin and vesicular glutamate transporter-2 (VGLUT2), showing that they were glutamatergic presynaptic terminals. Electron microscopic immunohistochemistry confirmed that CRLR immunoreactivity was present in axonal boutons that were not in synaptic glomeruli. Using tyramide signal amplification for double labeling with the CRLR and RAMP1 antibodies, we found some clear instances of colocalization of CRLR with RAMP1 in puncta, but their overall colocalization was low. In particular, CRLR was absent from RAMP1-containing cells. Many of the puncta stained for CRLR and RAMP1 were labeled by anti-opioid and anti-enkephalin antibodies. CRLR and, to a lesser extent, RAMP1 also colocalized with adrenergic alpha(2C) receptors. Triple label studies demonstrated three-way colocalization of CRLR-VGLUT2-synaptophysin, CRLR-VGLUT2-opioids, and CRLR-opioids-alpha(2C) receptors. In conclusion, CRLR is located in glutamatergic presynaptic terminals in the dorsal horn that contain alpha(2C) adrenergic receptors and opioids. Some of these terminals contain RAMP1, which may form CGRP receptors with CRLR, but in others CRLR may form other receptors, possibly by dimerizing with RAMP2 or RAMP3. These findings suggest that CGRP or adrenomedullin receptors modulate opioid release in the dorsal horn.