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A K Johnson

Publications and source records attributed to A K Johnson.

At least 163 records · Page 9Linked to original sources
PubMed1989

Selective central alpha-2 adrenoceptor control of regional haemodynamic responses to air jet stress in conscious spontaneously hypertensive rats.

The role of central nervous system alpha 2-adrenoceptors in the regulation of peripheral sympathetic outflow to regional vascular resistance beds during environmental stress was examined in conscious chronically instrumented spontaneously hypertensive rats (SHR). SHR were instrumented with pulsed Doppler flow probes on the renal and mesenteric arteries and the lower abdominal aorta. The mean arterial pressure (MAP), heart rate and regional vascular resistance responses to air jet stress were determined before and after cumulative administration of the alpha 2-adrenoceptor agonist, guanabenz, into the lateral cerebral ventricle in doses of 5 and 25 micrograms. Compared with intracerebroventricular (i.c.v.) administration of isotonic saline vehicle which did not affect baseline systemic and regional haemodynamic measurements, guanabenz produced significant decreases in baseline MAP and heart rate but did not affect regional vascular resistances. During air jet stress, the characteristic pattern of the classic defense reaction with an increase in MAP, heart rate, renal and mesenteric vascular resistances and a decrease in hindquarters vascular resistance was observed and was not affected by i.c.v. administration of isotonic saline vehicle. Guanabenz did not affect the MAP, heart rate or renal vascular resistance responses to air jet stress. The air jet stress-induced increase in mesenteric vascular resistance was reduced by 25 micrograms guanabenz. The air jet stress-induced decrease in hindquarters vascular resistance was converted to an increase by 25 micrograms guanabenz. These results demonstrate that the regulation of environmental stress-stimulated sympathetic neural outflow to different vascular beds may be independently controlled by central nervous system alpha 2-adrenoceptors.

Animals↗
PubMed1989

Effect of morphine on the hemodynamic and neuroendocrine responses to hemorrhage in conscious rats.

We have previously reported that analgesic doses of morphine accelerate mortality of rats exposed to hemorrhage (Feuerstein and Sirén: Circ Shock 19:293-300, 1986). To study the potential mechanisms involved in this phenomenon, rats were chronically implanted with catheters in the femoral vessels and morphine (1.5 or 5 mg/kg) was administered 30 min or 24 hr after bleeding (8.5 ml/300 g over 5 min) while arterial blood pressure and heart rate were continuously monitored. Furthermore, the effect of morphine (5 mg/kg) on cardiac output (CO) response to hemorrhage was studied in rats chronically equipped with a minithermistor for CO monitoring by a thermodilution technique. In addition, plasma catecholamines (HPLC), plasma renin activity (PRA, RIA), vasopressin (RIA), pH, and blood gases were also determined. Morphine administration 30 min after hemorrhage produced a pressor response and tachycardia which were in marked contrast to its depressor effect in intact rats. Morphine elevated PRA and epinephrine but not vasopressin, while blood pH and gases showed no consistent change as compared to saline-treated hemorrhaged rats. Morphine given after the bleeding resulted in enhanced cardiac depression in response to a second bleed of 2 ml/300 g. Our data suggest that activation of pressor mechanisms by morphine during hypovolemic hypotension might enhance vasoconstriction in essential organs, depress cardiac function, and further reduce effective tissue perfusion.

Animals↗
PubMed1988

Selective catecholamine depletion of structures along the ventral lamina terminalis: effects on experimentally-induced drinking and pressor responses.

Ablation of the periventricular tissue of the anteroventral third ventricle (AV3V) or injection of the chemical neurotoxin, 6-hydroxydopamine (6-OHDA), into the structures along the ventral lamina terminalis will produce deficits in drinking and pressor responses to exogenous angiotensin II (ANG II). Centrally-applied 6-OHDA has been shown to result in widespread depletions of both adrenergic (i.e. both noradrenaline and adrenaline-containing) and dopaminergic neurons. Questions arise, therefore, as to whether a dopaminergic or adrenergic depletion is critical and the locus where reductions must occur. The present experiment was designed to investigate the specificity of the effects of 6-OHDA administration into lamina terminalis-associated structures on ANG II-induced drinking and pressor responses. The nature of the depletion was manipulated with desmethylimipramine (DMI), a drug which blocks the uptake of 6-OHDA into adrenergic but not dopaminergic nerve terminals and thereby spares adrenergic elements. The experimental results indicate that 6-OHDA administration into structures of the ventral lamina terminalis produced ANG II response deficits and marked reductions in catecholamine histofluorescence in the regions of the injection sites. In contrast, pretreatment with DMI protected against the 6-OHDA-produced functional deficits and minimized the effects on histofluorescence. These findings are consistent with the interpretation that adrenergic but not dopaminergic neurons must be present in the structures of the ventral lamina terminalis in order to elicit normal angiotensin-induced drinking and pressor responses.

Adrenergic Fibers↗
PubMed1988

Role of the anteroventral third ventricle (AV3V) region of the rat brain in the pressor response to gamma 2-melanocyte-stimulating hormone (gamma 2-MSH).

We have examined the role of the anteroventral third ventricle (AV3V) region of the forebrain on the pressor responses to intravenous injections of the pituitary pressor agent, gamma 2-melanocyte-stimulating hormone (gamma 2-MSH) and the direct acting alpha 1-adrenergic agonist, phenylephrine in unanesthetized rats. Lesions of the AV3V region produce a parallel shift to the right in the dose response curve to gamma 2-MSH, with no effect on the pressor response to phenylephrine. The lesion had no effect on the heart rate response to either agent. These experiments indicate that the forebrain region surrounding the anterior third ventricle area is important to some of the cardiovascular actions of gamma 2-MSH.

Animals↗
PubMed1988

Renin-dependent water intake in hypovolemia.

The role of the renin-angiotensin system as a mediator of water intake, induced by hypovolemia after polyethylene glycol (PEG) injection, was investigated. Blockade of angiotensin I converting enzyme and of angiotensin receptors was used as a pharmacological tool. A significant reduction of water intake was observed when angiotensin I converting enzyme was inhibited by captopril and enalapril. In PEG-treated rats with blockade of angiotensin I converting enzyme, hypertonic saline injection continued to elicit substantial drinking. Normalization of low blood pressure by vasopressin infusions in PEG and captopril treated rats did not interfere with the antidipsogenic effectiveness of converting enzyme blockade. The angiotensin II receptor antagonist, saralasin, also reduced PEG-induced drinking although less effectively than converting enzyme inhibitors. We conclude that water intake due to isotonic depletion of the extracellular fluid compartment may depend on the activity of the renin-angiotensin system.

Angiotensin II↗
PubMed1988

Isolation, tactile startle and resting blood pressure in Long-Evans rats.

The effect of social isolation, consisting of individual housing in the vivarium under standard conditions and imposed on male rats older than 90 days, was assessed on tactile startle reactivity, nociception, resting heart rate and arterial blood pressure, and on intercorrelations among these variables. Tactile startle was affected by stimulus intensity, repeated trials and time of testing relative to the light/dark cycle, but not by social isolation from 1 to 29 days. Hot-plate latency was not affected by individual housing from 12 to 43 days. Blood pressure and heart rate were negatively correlated with isolation from 9 to 58 days, showing a significant decline over increasing days of isolation. Although not affected directly by isolation, tactile startle was affected secondarily by differences in blood pressure produced by individual housing. Rats with lower resting pressures responded to low-intensity startle stimuli that were not effective in rats with higher pressures, indicating a threshold difference and suggesting the hypothesis that blood pressure acts to modulate sensory reactivity.

Animals↗
PubMed1988

Sympathetic terminal mediation of the acute cardiovascular response of gamma 2-MSH.

Peptides of the ACTH4-10/gamma 2-MSH3-9 class produce pressor and cardioaccelerator effects upon i.v. administration. These actions appear to be mediated by peripheral catecholamines. To ascertain the role of sympathetic nerve terminals in the cardiovascular effects of these peptides, we used bretylium tosylate to prevent nerve terminal release of norepinephrine. Pretreatment with bretylium significantly attenuated the pressor and cardioaccelerator responses of gamma 2-MSH, and shifted the peak of the remaining responses to a later time point. It appears that the acute cardiovascular response to gamma-MSH administration depends primarily on the release of sympathetic terminal norepinephrine, though some contribution from other pressor systems such as adrenal catecholamines is possible.

Adrenocorticotropic Hormone↗
PubMed1988

Effects of adrenal demedullation on stress-induced hypertension and cardiovascular responses to acute stress.

Because chronic infusions of adrenalin (A) produce hypertension in rats, it has been suggested that A is a mediator of stress-induced hypertension. In order to test the hypothesis that lowering A will attenuate stress-induced hypertension, rats who had their adrenal medullae removed (ADM) and sham-operated controls were subjected to chronic stress. All subjects were offspring of a cross between spontaneously hypertensive and Wistar-Kyoto rats. Prior to chronic stress, systolic pressures were the same in the two groups. The stress consisted of 60 2-h sessions of shock-shock conflict during 18 weeks. After conflict stress, the rats were implanted with arterial catheters and allowed two days to recover. The resting mean arterial pressure (MAP) was 141.2 mmHg in the ADM group and 142.3 mmHg in the Sham group. Cardiovascular responses to acute stress were then examined. The rats were transferred to a test-box and subjected to pulsed foot shocks (0.5-s duration, 5-s intervals) for 5 min. The MAP increase after transfer was 22.3% in the ADM and 4.2% in the Shams (P less than 0.001). After termination of the shocks, the MAP was elevated 22.2% above baseline in the ADM and 8.1% in the Shams (P less than 0.02). Five minutes after foot shocks the MAP increase was 21.6% in the ADM and 7.2% in the Shams (P less than 0.02). Adrenal demedullation was effective in attenuating plasma A during stress and reduced the plasma noradrenaline response. Therefore, the larger pressor responses of the ADM group seem to result from attenuation of beta-adrenoreceptor-mediated dilation of skeletal muscle vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1987

Increased norepinephrine turnover in the median preoptic nucleus following reduced extracellular fluid volume.

The role of noradrenergic input to fluid balance regulatory systems in the anterior hypothalamus was studied by examination of norepinephrine (NE) turnover during reduction of systemic extracellular fluid volume. Extracellular fluid volume was decreased iso-osmotically by subcutaneous polyethylene glycol (PEG), known to increase thirst and vasopressin secretion. NE turnover was assessed by measuring the decline of NE concentration in brain micropunches after administration of alpha-methyl tyrosine in PEG- or sham-treated groups. Several hypothalamic areas were investigated, including the median preoptic area (MnPO), preoptic area (POA), paraventricular nucleus, supraoptic nucleus (SON), subfornical organ, ventromedial hypothalamus, and posterior hypothalamus. Volume-depleted animals showed significantly increased NE turnover in the MnPO, an important area for integration of fluid balance information. The POA and the SON also showed trends toward increased NE turnover. All other areas showed no difference in NE turnover between volume-depleted and normal animals. These results are consistent with previous findings that NE innervation to the MnPO is important in the control of fluid balance and also support the hypothesis that basal forebrain NE projections facilitate thirst and vasopressin secretion.

Animals↗
PubMed1987

Localized injections of 6-hydroxydopamine into lamina terminalis-associated structures: effects on experimentally induced drinking and pressor responses.

Electrolytic lesions of tissues surrounding the anteroventral third ventricle (AV3V) or injections of the chemical neurotoxin, 6-hydroxydopamine (6-OHDA) into the lateral cerebral ventricles result in virtually identical deficits in response to a variety of dipsogenic and pressor challenges. These observations have led to the hypothesis that the integrity of catecholamine (CA) projections into the AV3V region is a prerequisite for elicitation of these thirst and blood pressure responses. This hypothesis was tested in 6-OHDA-injected rats following protocols designed to deplete CA's in discrete structures associated with the lamina terminalis. Post-injection response deficits, coupled with histofluorescent assessments of CA depletions in specific anterior forebrain nuclei, support the stated hypothesis. In addition, the findings indicate that thirst deficits to systemic as well as central dipsogenic challenges are both selective and dissociable and that 6-OHDA lesions of any of the more ventrally situated target nuclei result in significantly attenuated blood pressure responses to centrally injected angiotensin II.

Angiotensin II↗
PubMed1987

Forebrain and brainstem afferents to the arcuate nucleus in the rat: potential pathways for the modulation of hypophyseal secretions.

Doxorubicin, an anti-oncogenic agent, was used as a retrograde marker to identify arcuate nucleus afferent projections. Injections of this tracer into the arcuate nucleus indicated that the subfornical organ, the organum vasculosum of the lamina terminalis, the nucleus raphe dorsalis and median raphe send projections to the arcuate nucleus. Immunocytochemical procedures were used to demonstrate that the raphe projections to the arcuate nucleus are serotoninergic. This anatomical investigation provides evidence that neural pathways exist between forebrain body fluid and mineral nuclei, mesencephalic serotonin nuclei and the arcuate nuclei.

Afferent Pathways↗
PubMed1987

Periventricular noradrenergic systems are critical for angiotensin-induced drinking and blood pressure responses.

Deficits in experimentally induced drinking and pressor responses after administration of 6-hydroxydopamine (6-OHDA) into the lateral cerebral ventricle (LCV) have been reported. Questions have arisen, however, as to whether these effects are due to non-specific actions of the neurotoxin and, if specific, whether the depletion of dopamine (DA) or of norepinephrine (NE) is the critical factor for producing the impairments. In the present report methods to deplete brain catecholamine (CA) differentially were employed in order to test the hypothesis that central 6-OHDA injections act on brain CA substrates per se to produce behavioral and physiological response deficits to angiotensin II (ANG II) challenges. The findings support the interpretation that forebrain dopamine is essential for the mediation of sensorimotor integration involved in response to acute homeostatic stressors. In addition, the outcome identifies an important role for forebrain noradrenergic systems in the mediation of ANG II-elicited drinking and blood pressure responses.

Angiotensin II↗
PubMed1987

Central serotonergic influences on renal electrolyte and water excretion.

These studies examined the effects of altered activity or levels of serotonin (5-HT) in the central nervous system (CNS) on renal water and excretion of electrolytes and on arterial blood pressure. Rats were implanted with intracerebroventricular cannulae and then continuously hydrated with a hypotonic solution in order to induce a diuresis. In two separate experimental series, samples of urine were collected before and after intraventricular (i.v.t.) administrations of drug, and the effects on the excretion of sodium were determined. In the first experimental series, 5-HT in the CNS was manipulated by intraventricular administration of p-chloroamphetamine (PCA), an agent known to increase synaptic concentrations of 5-HT. Significant increases in urinary excretion of sodium (UNa V) and the Na/K ratio were observed after the administration of p-chloroamphetamine (200-600 micrograms i.v.t.). p-Chloroamphetamine in large doses also increased blood pressure and antidiuresis. The natriuresis, but not the pressor or antidiuretic responses, were attenuated by pretreatment with either p-chlorophenylalanine, an inhibitor of tryptophan hydroxylase, or fluoxetine, a drug which inhibits the release of 5-HT following the administration of p-chloroamphetamine. Thus, the natriuretic response appeared to be due to a p-chloroamphetamine produced increase of synaptic 5-HT. A further test of the role of 5-HT in the central control of sodium excretion was made in a second experimental series where hydrated rats received intraventricular injections of 5-HT. After direct application of 5-HT to the CNS, significant increases in UNa V and in the Na/K ratio were observed, concomitant with depressor effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Regional vascular responses to an acute stressor in spontaneously hypertensive and Wistar-Kyoto rats.

The regional vascular responses to an acute intermittent footshock stressor were examined in Wistar-Kyoto and spontaneously hypertensive rats using the pulsed Doppler flow probe method. While both strains exhibited vascular resistance changes, which were typical of the 'defense response', the changes in regional vascular resistance were exaggerated in the spontaneously hypertensive rats compared to the Wistar-Kyoto. Despite these alterations in vascular resistance, and greater increases in heart rate in the spontaneously hypertensive rats, there were no differences in the pressor responses footshock between the Wistar-Kyoto and spontaneously hypertensive rats. These findings indicate that very specific regional hemodynamic changes accompany the characteristic sympathetic nervous system hyperresponsiveness of spontaneously hypertensive rats to environmental stress.

Animals↗
PubMed1987

Brain mechanisms and drinking: the role of lamina terminalis-associated systems in extracellular thirst.

Concomitants associated with alterations in body fluid balance serve as stimuli to appraise the brain of the momentary status of body salt and water. Extracellular fluid osmolality and the peptide ANG II have been identified as the humoral components that act as stimuli to trigger central receptors related to cellular and extracellular thirst, respectively. In the case of extracellular thirst, information about pressure/volume status is also obtained from systemic vascular receptors. It is proposed that peripherally-derived neural information is integrated with ANG II-related input within structures located in periventricular tissue of the AV3V.

Angiotensin II↗
PubMed1986

Response of supraoptic magnocellular neurons to stimulation of forebrain alpha-adrenoceptors.

Effects of alpha-adrenoceptor agents on electrophysiologically and immunohistochemically identified supraoptic nucleus (SON) vasopressin (VP) units were investigated by intracarotid infusion. Clonidine, an alpha 2-adrenoceptor agonist always excited SON units and alpha 2-adrenoceptor antagonists consistently inhibited them. alpha 1-Adrenoceptor agents produced inconsistent responses. The results implicate forebrain alpha 2-adrenergic receptors in the excitation of SON VP neurons.

Animals↗
PubMed1986

Neurohypophyseal hormone release and biosynthesis in rats with lesions of the anteroventral third ventricle (AV3V) region.

Lesions of the periventricular tissue surrounding the anteroventral third ventricle (AV3V) have been shown to disrupt body fluid homeostasis. The acute post-lesion phase in rats is characterized by adipsia, the lack of an appropriate antidiuretic response, and plasma vasopressin levels which do not rise. Electron micrographs of the supraoptic nucleus and neural lobe of lesioned adipsic rats suggest no stimulation of biosynthetic activity, and large stores of neurosecretory material in the axon terminals. To directly investigate the status of these neurons, we determined neural lobe vasopressin and oxytocin content and the incorporation of [35S]cysteine into hypothalamic proteins in rats with sham-lesions or lesions of the AV3V after 3 days of adipsia or water deprivation, and in water replete sham-lesioned rats. The results demonstrate that adipsic rats with AV3V lesions have neural lobe vasopressin and oxytocin content equivalent to water-replete sham-lesioned rats. Neural lobe vasopressin and oxytocin levels of water-deprived sham-lesioned rats were significantly below those of all other groups. In addition, this group had a radioactivity incorporation rate into hypothalamic proteins which was two-fold greater than either of the other groups. The results indicate that 3-day adipsic AV3V-lesioned rats do not increase neurohypophyseal hormone release or biosynthesis as do 3-day water-deprived sham-lesioned rats. The periventricular tissue of the AV3V would therefore appear to be crucial in providing information to the hypothalamo-neurohypophyseal neurons on body fluid homeostasis.

Animals↗