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Biomedical subjects

D S Goldstein

Publications and source records attributed to D S Goldstein.

At least 145 records · Page 8Linked to original sources
PubMed1994

On the existence of functional beta-adrenoceptors on vascular sympathetic nerve endings in the human forearm.

OBJECTIVE: To examine the existence of presynaptic beta-adrenoceptors modulating forearm norepinephrine release in 31 healthy volunteers. METHODS: The spillover rate of norepinephrine in forearm venous plasma and the total plasma appearance rate of norepinephrine in the forearm were estimated using intra-arterial infusion of [3H]-norepinephrine. Isoprenaline was infused intra-arterially to stimulate beta-adrenoceptors, terbutaline to stimulate beta 2-adrenoceptors, propranolol to block beta-adrenoceptors, metoprolol to block beta 1-adrenoceptors, isoprenaline combined with metoprolol to stimulate beta 2-adrenoceptors, epinephrine to stimulate alpha- and beta-adrenoceptors, yohimbine to block alpha 2-adrenoceptors and sodium nitroprusside to increase forearm blood flow directly. RESULTS: No systemic hemodynamic effects or changes in arterial plasma norepinephrine level were noted during the intra-arterial infusions. Metoprolol and propranolol decreased norepinephrine spillover and its rate of appearance in the forearm without affecting forearm blood flow. Isoprenaline and sodium nitroprusside increased and epinephrine decreased forearm norepinephrine spillover. Terbutaline increased forearm norepinephrine spillover and its rate of appearance in the forearm. Terbutaline increased the forearm rate of appearance and spillover of norepinephrine more than did sodium nitroprusside or isoprenaline at the same level of forearm blood flow. Infusion of isoprenaline failed to increase norepinephrine spillover or its forearm appearance rate more than would be expected from the increase in forearm blood flow. Administration of epinephrine increased spillover and forearm appearance rate of norepinephrine during intra-arterial infusion of yohimbine. CONCLUSIONS: The terbutaline, propranolol, metoprolol and yohimbine plus epinephrine results suggest that beta-adrenoceptors enhance release of norepinephrine from vascular sympathetic nerve endings in humans.

Adult↗
PubMed1994

6-[Fluorine-18]fluorodopamine pharmacokinetics and dosimetry in humans.

UNLABELLED: PET scanning after injection of 6-[18F]fluorodopamine visualizes tissue sympathetic innervation. Organ dosimetric estimates for 6-[18F]fluorodopamine have relied on studies of rats and dogs and on literature about the fate of other radiolabeled catecholamines. This report uses empirical clinical findings in healthy volunteers to refine and extend these estimates. METHODS: Thoracic PET scanning was conducted and arterial blood and urine samples were obtained after intravenous injection of 6-[18F]fluorodopamine into 10 normal volunteers. RESULTS: The main target organs for 6-[18F]fluorodopamine-derived radioactivity were the wall of the urinary bladder (3.3 rem for a 4-mCi dose and 3.31-hr voiding interval) and the kidneys (2.9 rem for a 4-mCi dose) due to urinary excretion of radioactive metabolites of [18F]-6F-DA. The estimates were about one-fourth those predicted from studies of laboratory animals. CONCLUSIONS: At administered doses required to visualize the left ventricular myocardium in humans, a 6-[18F]fluorodopamine injection produces acceptable absorbed radiation doses, with the highest doses to the urinary collecting system.

Adult↗
PubMed1993

Plasma and cerebrospinal fluid neurochemical pattern in Menkes disease.

Menkes disease is a neurodegenerative disorder of copper metabolism. Because the enzyme dopamine-beta-hydroxylase requires copper to catalyze the conversion of dopamine to norepinephrine, we reasoned that patients with Menkes disease would have a neurochemical pattern similar to that seen in patients with congenital absence of dopamine-beta-hydroxylase, i.e., high levels of dopamine, the dopamine metabolite dihydroxyphenylacetic acid (DOPAC), and the catecholamine precursor dihydroxyphenylalanine (DOPA), and low levels of norepinephrine and its neuronal metabolite dihydroxyphenylglycol (DHPG). We measured plasma and cerebrospinal fluid (CSF) levels of catechols in 10 patients ranging in age from 9 days to 27 months. In contrast to patients with congenital absence of dopamine-beta-hydroxylase, norepinephrine levels were normal in plasma of 4 Menkes patients and in CSF of all 10 patients. However, the ratios of DOPA:DHPG and DOPAC:DHPG in plasma and CSF of Menkes patients were invariably increased beyond the ranges of control values. These neurochemical findings indicate partial deficiency of dopamine-beta-hydroxylase in Menkes patients, with compensatory increases in catecholamine biosynthesis in sympathetic nerves and in the brain. Increased tyrosine hydroxylation and increased exocytotic release of norepinephrine may be responsible for preservation of plasma and CSF norepinephrine levels in Menkes patients. The abnormal neurochemical pattern, including high ratios of DOPA:DHPG and DOPAC:DHPG, may serve as a biochemical marker for Menkes disease and provide a baseline against which the influence of proposed therapies can be judged.

Adult↗
PubMed1993

Chronic inhibition of monoamine oxidase type A increases noradrenaline release in rat frontal cortex.

Chronic but not acute treatment of rats with MAO inhibitors, as with other antidepressant drugs, has been shown to down-regulate the number of cerebro-cortical beta-adrenoceptors. In order to establish whether this effect is associated with an increase in cortical noradrenaline release, rats were treated for 1, 3 or 21 days with clorgyline (2 mg/kg i.p. single injection; 1 mg/kg i.p. repeated injections), and the frontal cortex was then perfused by microdialysis in the awake animal. Control animals were injected with saline. The concentration of noradrenaline in the microdialysate increased only slightly after 1 or 3 days of clorgyline treatment but increased fourfold over control levels after 21 days treatment. Yohimbine (20 mumol/l) added to the perfusing solution caused a similar degree of enhancement in microdialysate noradrenaline concentration in all groups of rats. Tetrodotoxin (10 mumol/l) reduced noradrenaline concentration to low levels in all groups of animals, but noradrenaline was still detectable in the microdialysate in rats treated with clorgyline for 21 days. Concentrations of the deaminated metabolites dihydroxyphenylacetic acid, dihydroxyphenylglycol and methoxy-hydroxyphenylglycol were lowest after the 21 day clorgyline treatment. Determination of enzyme activity ex vivo showed that MAO-A was inhibited more than 95% by all clorgyline treatments with less than 10% inhibition of MAO-B. The results indicate that cerebrocortical noradrenaline release increases gradually during chronic MAO inhibition. This may be the result of more complete inhibition of the enzyme with time, not detectable by the ex vivo assay, but shown by the progressive reduction in metabolite levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Plasma catecholamine, renin activity, and ACTH responses to the serotonin receptor agonist DOI in juvenile spontaneously hypertensive rats.

Mean arterial blood pressure (MAP), heart rate (HR) and arterial plasma levels of corticotropin (ACTH), renin activity (PRA) and catechols [norepinephrine (NE), epinephrine (EPI), and the intraneuronal NE metabolite dihydroxyphenylglycol (DHPG)] at baseline and in response to the serotonin-1C/2 (5-HT1C/5-HT2) agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI, 1.0 mg/kg i.a.) in conscious, freely-moving, juvenile (4 week old) spontaneously hypertensive rats (SHR's) and age-matched Wistar-Kyoto (WKY) normotensive control rats were measured simultaneously. Baseline levels of MAP, NE, DHPG, and EPI all were significantly higher in the SHR's. There was a similar trend for PRA, but ACTH did not differ between the two strains. DOI produced marked increases in levels of MAP, ACTH, EPI, and also PRA but did not affect NE or DHPG concentrations. HR decreased only in the WKY group after administration of DOI. The magnitudes of the EPI and ACTH responses did not differ between the rat strains. Responses of MAP and PRA were significantly larger in SHR's. These results suggest that there is a selective hyperresponsiveness of PRA and blood pressure to 5-HT2 receptor stimulation parallel to a deficient baroreceptor reflex in juvenile SHR's.

Adrenocorticotropic Hormone↗
PubMed1993

Positron emission tomographic imaging of cardiac sympathetic innervation using 6-[18F]fluorodopamine: initial findings in humans.

OBJECTIVES: This study evaluated the safety, efficacy and validity of 6-[18F]fluorodopamine positron emission tomographic scanning of cardiac sympathetic innervation and function in humans. METHODS: Positron emission tomography (PET) scans, arterial blood and urine were obtained after a 3-min intravenous infusion of 6-[18F]fluorodopamine (1 to 4 mCi, 188 to 809 mCi/mmol) in healthy volunteers, with or without pretreatment with oral desipramine to inhibit neuronal uptake of catecholamines. RESULTS: 6-[18F]Fluorodopamine PET scanning visualized the left ventricular myocardium. Blood pressure increased slightly and transiently. The estimated absorbed radiation dose to the main target organ, the wall of the urinary bladder, was 0.8 to 1.0 rad/mCi of injected 6-[18F]fluorodopamine. By 24 h after the injection, the main 6F-compound in urine was 6F-vanillymandelic acid, a metabolite of 6F-norepinephrine. Desipramine attenuated accumulation of myocardial 6-[18F]fluorodopamine-derived radioactivity and plasma 6F-dihydroxyphenylacetic acid. CONCLUSIONS: 6-[18F]Fluorodopamine produces negligible hemodynamic effects and acceptable radiation exposure at doses that visualize the left ventricular myocardium. Sympathetic nerves take up 6-[18F]fluorodopamine, which is translocated from the axoplasm into storage vesicles, where is it beta-hydroxylated to the fluorinated analogue of the sympathetic neurotransmitter norepinephrine. Therefore, the basis for visualization of myocardium after 6-[18F]fluorodopamine injection in humans is radiolabeling by 6-[18F]fluorodopamine and 6-[18F]fluoronorepinephrine of vesicles in sympathetic terminals. 6-[18F]Fluorodopamine PET scanning provides a novel means for assessing sympathetic innervation and function noninvasively in the human heart.

Adult↗
PubMed1993

Laparoscopic correction of vesicoureteral reflux.

Major advances have been made in the area of laparoscopic surgery. The advantages of this approach include smaller incisions, shorter hospitalizations, a more rapid convalescence and decreased postoperative discomfort. To explore the technical feasibility of performing antireflux surgery laparoscopically, we conducted a pilot study in 4 mini-pigs in which bilateral vesicoureteral reflux had been created surgically. We applied a modification of the Lich extravesical ureteral approach to perform laparoscopic antireflux surgery. All mini-pigs underwent successful unilateral mobilization, creation of a bladder wall trough and creation of a new ureteral tunnel laparoscopically. Examinations were performed postoperatively, and then serially at 1, 2, 3 and 5 months after repair. Fluoroscopic cystograms demonstrated the resolution of reflux in the corrected ureters and persistence of reflux in the uncorrected control ureters in all animals. Excretory urography showed no evidence of obstruction. Laparoscopic correction of vesicoureteral reflux appears to be technically feasible in the animal model. Long-term followup is necessary to determine the possible applicability of this technique in humans.

Animals↗
PubMed1993

Derivation of urinary dopamine from plasma dihydroxyphenylalanine in humans.

1. Dihydroxyphenylalanine is the precursor of all endogenous catecholamines. In laboratory animals, renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounts for most of dopamine in urine. Dopamine is natriuretic, and in rats, dietary salt loading increases renal dihydroxyphenylalanine uptake by increasing the rate of entry (spill-over) of dihydroxyphenylalanine into arterial plasma. In experimental animals and in humans, dietary salt loading increases urinary excretion of dihydroxyphenylalanine and dopamine. The present study examined in humans the extent to which circulating dihydroxyphenylalanine is the source of urinary dopamine and of the dopamine metabolite dihydroxyphenylacetic acid, and whether, as in animals, dietary salt loading affects dihydroxyphenylalanine spillover. 2. L-Dihydroxyphenylalanine (0.33 micrograms min-1 kg-1) was infused intravenously for 300 min after 7 days of a low-salt (mean 41 mmol/day) or a high-salt (mean 341 mmol/day) diet in 12 healthy subjects. Concentrations of dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid were measured in urine and in antecubital venous plasma. Infusion of L-dihydroxyphenylalanine produced a steady-state mean dihydroxyphenylalanine level about 10 times the endogenous level. About 30% of infused dihydroxyphenylalanine estimated to be delivered to the kidneys via the arterial plasma was excreted as dopamine, and about 30% was excreted as dihydroxyphenyl-acetic acid. 3. Dietary salt loading increased urinary excretion rates of dihydroxyphenylalanine [from 0.08 +/- (SEM) 0.01 to 0.14 +/- 0.03 nmol/min, t = 2.80, P < 0.02] and dopamine (from 1.03 +/- 0.19 to 1.30 +/- 0.28 nmol/min, t = 2.35, P < 0.05), whereas dihydroxyphenylalanine spillover appeared to be unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Inhibition of peritoneal tumor-cell implantation: model for laparoscopic cancer surgery.

A serious concern in applying laparoscopic surgery to malignancies is the possibility of tumor spillage and seeding. We developed a model of peritoneal tumor implantation using a murine bladder tumor cell line, MBT-2. Anesthetized C3H male mice underwent mock laparoscopy with or without peritoneal disruption and instillation of tumor cells via a 16-gauge angiocatheter, and the effect of heparin and the pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS) on tumor cell adherence and growth was evaluated. Animals were divided into six groups: Group 1 = tumor cells only; Group 2 = peritoneal disruption + tumor cells; Group 3 = heparin + tumor cells; Group 4 = peritoneal disruption + heparin + tumor cells; Group 5 = GRGDS + tumor cells; and Group 6 = peritoneal disruption + GRGDS + tumor cells. In all animals, a greater tumor burden was noted at the sites of peritoneal disruption. Moreover, 50% and 63% of animals in Groups 1 and 2 developed tumors compared with 17% and 31% of those in Groups 3 and 4, respectively. There was significantly more tumor at the sites of peritoneal disruption in the "tumor only" groups than in those that received heparin (mean tumor volume 32.32 mm3 in Group 2 v 2.77 mm3 in Group 4; p < 0.05). The GRGDS-treated groups showed a trend toward decreased number and size of tumors compared with the tumor only groups, although the differences were not statistically significant. These findings imply that prophylactic irrigation with substances that decrease cell adherence may prevent tumor implantation after accidental intraoperative tumor spillage.

Amino Acid Sequence↗
PubMed1993

Oral yohimbine increases blood pressure and sympathetic nervous outflow in hypertensive patients.

Yohimbine is an alpha 2-adrenoceptor antagonist that is FDA approved for treatment of impotence. The drug is an indolalkylamine alkaloid chemically similar to reserpine and is believed to act through sympatholysis. We examined effects of oral yohimbine on blood pressure (BP) and plasma levels of catechols in patients with essential hypertension, a condition in which most drug treatments can produce impotence. In 25 unmedicated hypertensive subjects, vital signs were measured and blood samples were obtained through an indwelling antecubital venous catheter at baseline and 1 and 2 h after subjects ingested 4 5.4-mg tablets of yohimbine. Mean blood pressure (MBP) increased by an average of 5 mm Hg (p < 0.01), plasma norepinephrine (NE) levels increased by 66% (p < 0.001), and plasma dihydroxyphenylglycol (DHPG) levels increased by 25% (p < 0.01) at 1 h after drug administration. The magnitude of the pressor response was unrelated to baseline MBP but positively correlated with the baseline NE level (r = 0.61, p < 0.01) and with the yohimbine-induced increment in plasma NE (r = 0.4, p < 0.01). The results indicate that yohimbine does not inhibit and actually stimulates sympathetically mediated NE release in humans and that the increased NE release produces a pressor response. Yohimbine should be administered with caution to patients with high BP, especially in individuals with evidence for increased basal sympathetic outflow or those undergoing concurrent treatment with tricyclic antidepressants or other drugs that interfere with neuronal uptake or metabolism of NE.

Administration, Oral↗
PubMed1993

Role of CRH in glucopenia-induced adrenomedullary activation in rats.

Acute glucoprivation profoundly stimulated hypothalamic-pituitary-adrenocortical (HPA) and adrenomedullary outflows. Whether these responses reflect a single central mechanism regulated by corticotropin-releasing hormone (CRH) has been unclear. This study examined the role of endogenous CRH in HPA and adrenomedullary responses to hypoglycemia in Sprague-Dawley rats, by using anti-CRH immune serum or a CRH antagonist (alpha-helical h/r CRH9-41, and in Lewis rats, a strain characterized by deficient hypothalamic CRH responses during stress. In conscious Sprague-Dawley rats with indwelling arterial and venous cannulas, insulin (0.3 U/kg was injected iv, and responses of serum glucose concentrations and plasma levels of corticotropin (ACTH) and catechols (including epinephrine, EPI; norepinephrine, NE; dihydroxyphenylalanine, DOPA; dihydroxyphenylglycol, DHPG; and dihydroxyphenylacetic acid, DOPAC) were assessed, with or without pretreatment with anti-CRH immune serum (0.5 or 1.0 ml iv or 10 microl icv) or alpha-helical h/r CRH9-41 (130 nmol iv or 13 nmol icv). Responses to insulin (1.0 U/kg iv) were also measured in conscious juvenile Lewis and Fischer 344/N rats. Insulin-induced hypoglycemia markedly increased plasma levels of EPI and ACTH in all groups. Pretreatment iv with 1/0 ml of anti-CRH immune serum blocked the ACTH response to insulin but failed to attenuate the EPI response. alpha-helical h/r CRH9-41, whether given iv or icv, failed to alter ACTH or EPI responses to insulin, although the antagonist did block EPI responses to icv CRH. Hypoglycemia elicited similar increments in ACTH levels in Lewis rats and Fischer 344/N control rats; and although Lewis rats had lower baseline EPI and smaller responses of NE, DHPG, DOPA, and DOPAC levels, the groups did not differ in proportionate increments in EPI levels. The results indicate that the ACTH response to hypoglycemia depends on availability of CRH outside the blood-brain barrier--presumably in the pituitary gland. The findings with icv alpha-helical h/r CRH9-41 can be explained by failure of the antagonist to reach effective concentrations at central sites of action of endogenous CRH, or by mechanisms other than CRH release determining the adrenomedullary response to hypoglycemia. Lewis rats seem to have less adrenomedullary secretion at baseline and smaller responses of NE synthesis and release during hypoglycemia than do Fischer 344/N rats. Neurochemical evidence for differential adrenomedullary and sympathoneural responses during hypoglycemia in all three rat strains is inconsistent with Cannon's view of a functionally unitary sympathoadrenal system. Lewis rats have deficient CRH responses to some stressors but not to others, or else pituitary-adrenomedullary responses in this setting depend on mechanisms other than CRH release in the brain. Both explanations are inconsistent with the doctrine of non-specificity, the main tenet of Selye's stress theory.

Adrenal Medulla↗
PubMed1993

Glycine stimulates striatal dopamine release in conscious rats.

1. Glycine is an inhibitory neurotransmitter in the spinal cord and brainstem. The mechanism of this inhibition is via binding of glycine to specific receptors, increasing transmembrane Cl- conductance and hyperpolarizing neurones. Strychnine selectively antagonizes these effects. The role of glycinergic neurones in supraspinal regions is poorly understood. 2. Effects of glycine on release of catecholamines in the striatum were examined by microdialysis in freely-moving rats. Transcription of the genes encoding strychnine-sensitive glycine receptors was assessed in the striatum and substantia nigra, by use of reverse transcription followed by the polymerase chain reaction. 3. Glycine administered via the microdialysis probe dose-dependently increased concentrations of dopamine and its metabolites, dihydroxyphenylacetic acid and homovanillic acid, in the perfusate, indicating increased local release and metabolism of dopamine. Strychnine markedly attenuated these responses. Whereas striatal tissue did not contain mRNA for either the adult or neonatal form of strychnine-sensitive glycine receptor, nigral tissue contained a message for the adult form. 4. The results suggest that dopaminergic cells in the substantia nigra synthesize strychnine-sensitive glycine receptors and transport the receptors to terminals in the striatum. Occupation of the glycine receptors then exerts a net stimulatory effect on striatal dopamine release in vivo.

Animals↗
PubMed1993

Mechanisms underlying cardiovascular defense reaction evoked by dorsal periaqueductal gray stimulation.

Hemodynamic and autonomic mechanisms underlying the cardiovascular defense reaction elicited by electrical stimulation of the dorsolateral periaqueductal gray region were evaluated in pentobarbital sodium-anesthetized Sprague-Dawley rats. Stimulation of this area produced transient increases in mean arterial pressure and more sustained increases in heart rate, hindlimb blood flow, and plasma catecholamine levels. The pressor component of the defense reaction was due entirely to increased total peripheral vascular resistance; elevations in cardiac output occurred only at the end of the stimulation period when blood pressure had returned to resting values. The hindlimb vasodilatory response included distinct early and late components. The late component was produced by epinephrine-mediated activation of beta 2-receptors because it was abolished by bilateral adrenalectomy or treatment with butoxamine, a beta 2-receptor selective antagonist. In contrast, the early component was only partially reduced by adrenalectomy or butoxamine treatment. During conditions of constant flow provided by a pump-perfused hindlimb preparation, the early hindlimb vasodilatory response was eliminated and a neurogenic vasoconstrictor response revealed. This finding suggests that the early hindlimb blood flow response may result from shunting of blood from highly vasoconstricted vascular beds to relatively less constricted hindlimb vasculature.

Adrenalectomy↗
PubMed1993

Modified microdialysis probe for sampling extracellular fluid and administering drugs in vivo.

In vivo microdialysis provides an important new tool for investigating changes in extracellular fluid levels of endogenous compounds in vivo. Delivery of drugs via the microdialysis probe can be used to study local release and metabolism of neurotransmitters, but the dialysis membrane limits diffusion of substances between the perfusate and the extracellular fluid. Thus there may be considerable delay in responses, drug concentrations at the effector sites are less than those in the probe, and high-molecular-weight substances cannot traverse the membrane at all. This report describes a simple modification of commercially available microdialysis probes. A cannula is glued to the external surface of the probe. When glycine was administered via the cannula into the striatum of conscious rats, increments in microdialysate concentrations of dopamine were at least 10 times greater than when glycine was administered via the dialysis fluid in the probe. The threshold glycine dose for behavioral (turning) effects was also decreased by approximately 60-fold, and the time to the peak neurochemical and behavioral effects was markedly decreased. The modified probe did not destroy local catecholaminergic cells, as indicated by tyrosine hydroxylase immunofluorescence. Use of the modified microdialysis probe should facilitate pharmacological and neuroendocrine studies in behaving animals.

Animals↗
PubMed1993

Effects of single or repeated immobilization on release of norepinephrine and its metabolites in the central nucleus of the amygdala in conscious rats.

The release of norepinephrine (NE) and its metabolites in the central nucleus of the amygdala was measured using in vivo microdialysis during immobilization (IMMO) stress in conscious rats. Animals underwent 2-hour periods of IMMO either once or daily for 7 days. Extracellular fluid concentrations of NE, dihydroxyphenylglycol (DHPG), methoxyhydroxyphenylglycol (MHPG), and the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) were measured before, during, and after IMMO. Microdialysate levels of NE and DHPG attained 2- to 3-fold increments during the 1 h of IMMO and declined thereafter, whereas MHPG and DOPAC levels attained maximal levels of about twice basal concentrations during the 2- or 3-h after initiation of IMMO. After the sixth IMMO basal levels of NE, DHPG, MHPG, and DOPAC were decreased, and NE, DHPG, and DOPAC responses during the seventh IMMO failed to attain levels found during the first IMMO, although the absolute changes during IMMO were similar between animals subjected to IMMO once or seven times. The results indicate that acute IMMO increases synthesis, release, and metabolism of NE in the central nucleus of the amygdala and that repetition of IMMO decreases basal catecholamine synthesis and noradrenergic turnover in this brain region, without inhibiting acute noradrenergic responses.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Stress-induced norepinephrine release in the paraventricular nucleus of rats with brainstem hemisections: a microdialysis study.

Immobilization (IMMO) of conscious rats evokes marked increases in release of norepinephrine (NE) in the paraventricular nucleus (PVN) of the hypothalamus, consistent with a role of NE in the PVN release of corticotropin-releasing hormone and therefore in pituitary-adrenocortical activation during stress. The present study examined the effects of surgical hemisection of the brainstem between the locus ceruleus and rostral portion of the medulla on release of NE in the PVN of the hypothalamus in vivo in conscious rats, at baseline and during IMMO. Concentrations of NE, the intraneuronal NE metabolite dihydroxyphenylglycol (DHPG), and the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) were measured in microdialysate samples obtained beginning 24 h after implantation of a microdialysis probe in the PVN either ipsilateral or contralateral to the hemisection. On the lesioned side, baseline levels of NE, DHPG, and DOPAC were significantly lower and IMMO-induced increases were smaller than in sham-operated rats. Contralateral to the hemisection, DOPAC levels were significantly reduced. Neither baseline levels nor IMMO-induced increases in plasma corticosterone levels differed between lesioned and sham-operated animals. The present results indicate that: (1) NE release in the PVN at baseline and during IMMO depends mainly on ascending medullary tracts from ipsilateral brainstem A1 and A2 catecholaminergic areas, with small contributions from the locus ceruleus and from contralateral medullary cells, and (2) brainstem hemisection does not influence IMMO-induced activation of the hypothalamic-pituitary-adrenocortical axis as indicated by plasma corticosterone levels in conscious rats.

Animals↗
PubMed1993

Influence of cigarette smoking on human autonomic function.

BACKGROUND: Although cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control. METHODS AND RESULTS: We studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction. Smoking provoked the following changes: Arterial pressure increased significantly, and RR intervals, RR interval spectral power at the respiratory frequency, and muscle sympathetic nerve activity decreased. Plasma nicotine levels increased significantly, but plasma epinephrine, norepinephrine, and neuropeptide Y levels did not change. Peak sympathetic nerve activity during and systolic pressure overshoots after Valsalva straining increased significantly in proportion to increases of plasma nicotine levels. The average carotid baroreceptor-cardiac reflex relation shifted rightward and downward on arterial pressure and RR interval axes; average gain, operational point, and response range did not change. CONCLUSIONS: In habitual smokers, smoking acutely reduces baseline levels of vagal-cardiac nerve activity and completely resets vagally mediated arterial baroreceptor-cardiac reflex responses. Smoking also reduces muscle sympathetic nerve activity but augments increases of sympathetic activity triggered by brief arterial pressure reductions. This pattern of autonomic changes is likely to influence smokers' responses to acute arterial pressure reductions importantly.

Adult↗