Biomedical subjects

A F Sved

Publications and source records attributed to A F Sved.

At least 55 records · Page 3Linked to original sources

PubMed1999

Sodium excretion and renin secretion after continuous versus pulsatile infusion of oxytocin in rats.

Neurohypophyseal oxytocin (OT), secreted continuously under conditions of hyperosmolality, is a potent natriuretic hormone in rats. In contrast, OT secretion during lactation is pulsatile and is not accompanied by increased urinary Na+ excretion. The present experiments compared the effects of continuous and pulsatile infusion of OT on natriuresis in rats. In male rats anesthetized with Inactin, continuous infusion of OT (125 ng/kg x h) increased plasma OT to about 70 pg/ml; renal Na+ excretion increased 10-fold, and urine volume and K+ excretion also were elevated. However, when OT was administered i.v. in the same amount but in pulses given once every 5 or 10 min, to simulate the pattern of OT secretion during lactation, rats did not excrete significantly more urine, Na+, or K+ than did vehicle-treated animals. The plasma renin concentration, measured in these experiments because OT receptors are present in the macula densa, increased 2-fold when OT was infused either continuously or in pulses. These results indicate that the effects of OT administration on urinary Na+ excretion in rats varies depending on whether the infusion is pulsatile or continuous, whereas the effects of OT on renin secretion show no such difference.

Animals↗

PubMed1998

Role of excitatory amino acids in the regulation of dopamine synthesis and release in the neostriatum.

We have explored the role of excitatory amino acids in the increased dopamine (DA) release that occurs in the neostriatum during stress-induced behavioral activation. Studies were performed in awake, freely moving rats, using in vivo microdialysis. Extracellular DA was used as a measure of DA release; extracellular 3,4-dihydroxyphenylalanine (DOPA) after inhibition of DOPA decarboxylase provided a measure of apparent DA synthesis. Mild stress increased the synthesis and release of DA in striatum. DA synthesis and release also were enhanced by the intra-striatal infusion of N-methyl-D-aspartate (NMDA), an agonist at NMDA receptors, and kainic acid, an agonist at the DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA)/kainate site. Stress-induced increase in DA synthesis was attenuated by co-infusion of 2-amino-5-phosphonovalerate (APV) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), antagonists of NMDA and AMPA/kainate receptors, respectively. In contrast, intrastriatal APV, CNQX, or kynurenic acid (a non-selective ionotropic glutamate receptor antagonist) did not block the stress-induced increase in DA release. Stress-induced increase in DA release was, however, blocked by administration of tetrodotoxin along the nigrostriatal DA projection. It also was attenuated when APV was infused into substantia nigra. Thus, glutamate may act via ionotropic receptors within striatum to regulate DA synthesis, whereas glutamate may influence DA release via an action on receptors in substantia nigra. However, our method for monitoring DA synthesis lowers extracellular DA and this may permit the appearance of an intra-striatal glutamatergic influence by reducing a local inhibitory influence of DA. If so, under conditions of low extracellular DA glutamate may influence DA release, as well as DA synthesis, by an intrastriatal action. Such conditions might occur during prolonged severe stress and/or DA neuron degeneration. These results may have implications for the impact of glutamate antagonists on the ability of patients with Parkinson's disease to tolerate stress.

Animals↗

PubMed1998

Acquisition of nicotine self-administration in rats: the effects of dose, feeding schedule, and drug contingency.

The studies presented here were designed to further clarify the nature of nicotine self-administration (SA) based on a limited access model in which rats are food restricted, receive operant training using food reinforcement, and are then tested in daily 1-h drug sessions. We examined the effects of dose, feeding schedule, and contingency of drug delivery on acquisition of nicotine SA. Two doses of nicotine bitartrate, 0.03 and 0.06 mg/kg per infusion (free base), supported the transition from food-reinforced to drug-reinforced responding, although the pattern of behavior differed between these doses. In contrast, 0.01 mg/kg per infusion failed to maintain nicotine SA. In a second study, animals were divided into three groups according to feeding schedule. Rats that were both weight restricted and food deprived showed the highest level of SA behavior, although neither food deprivation nor weight restriction was necessary to establish SA. In the third experiment, rats that were switched from food to nicotine as the response-dependent reinforcer maintained higher response rates throughout a 9-day period than animals switched to response-independent (i.e., yoked) nicotine which showed minimal responding after day 1. Furthermore, the differences between self-administering and yoked animals emerged during the first session, suggesting that nicotine may serve as a reinforcer during the first drug exposure in naive animals. These results indicate that acquisition of nicotine SA can be influenced by both dose of nicotine and feeding schedule and that, in animals previously trained on a food-reinforced operant, active lever pressing is maintained only when nicotine delivery is contingent upon responding.

Animals↗

PubMed1998

Injection of corticotropin-releasing hormone into the locus coeruleus or foot shock increases neuronal Fos expression.

Previous research suggests that corticotropin-releasing hormone can act in the locus coeruleus to increase the firing of locus coeruleus neurons and elicit physiological responses resembling those associated with stress. The present study used immunocytochemical detection of Fos as a measure of neuronal activation to identify brain areas that were activated by bilateral injections of corticotropin-releasing hormone into the locus coeruleus of rats. Injection of corticotropin-releasing hormone into the locus coeruleus increased the expression of Fos in the locus coeruleus as compared with injection of vehicle into the locus coeruleus or injection of corticotropin-releasing hormone into neighbouring pontine sites. The pattern of Fos expression throughout the brain after injections of corticotropin-releasing hormone into the locus coeruleus was generally consistent with the anatomical organization of efferent projections arising from the locus coeruleus; increased Fos expression was observed in many brain areas including the ventral lateral septum, septohypothalamic nucleus, bed nucleus of the stria terminalis, the central amygdaloid nucleus, the dorsomedial nuclei of the hypothalamus, and the thalamic paraventricular and rhomboid nuclei. Foot shock also increased Fos expression in the locus coeruleus and the other brain regions that expressed Fos after corticotropin-releasing hormone injections into the locus coeruleus. A few brain regions, most notably the hypothalamic paraventricular nucleus, expressed Fos in response to foot shock but not corticotropin-releasing hormone. These results indicate that local injection of corticotropin-releasing hormone into the locus coeruleus stimulates the activity of the locus coeruleus neurons. However, the pattern of Fos expression throughout the brain evoked by injection of corticotropin-releasing hormone into the locus coeruleus does not fully replicate the effects of foot shock.

Animals↗

PubMed1998

The role of corticosteroids in nicotine's physiological and behavioral effects.

This paper reviews evidence indicating that adrenal corticosteroids modulate the responsiveness of mice and rats to nicotine. Adrenalectomy increases, and both acute and chronic corticosteroid administration decrease, some of the physiological and behavioral effects of nicotine. One function of adrenal steroids may be to regulate stress-induced changes in nicotine sensitivity. Another is to mediate the development of chronic tolerance when nicotine is given intermittently, and when the resulting tolerance has a learned component. A role of glucocorticoids in the development of tolerance to nicotine is suggested by the findings that a conditioned elevation of plasma corticosterone, which anticipates nicotine delivery, accompanies the development of chronic tolerance and that environmental cues evoke a conditioned corticosterone response, but only after they have become associated with nicotine delivery. The mechanisms by which adrenal steroids modulate nicotine sensitivity are not known, although recent in vitro evidence suggests that steroids can rapidly and reversibly reduce nicotinic receptor function. While most of the data are consistent with the hypothesis that corticosteroids reduce nicotine responsiveness, and thus promote a learned form of tolerance, there are new findings that corticosteroids increase the development of sensitization to the locomotor-activating effects of nicotine. These data suggest that formulations postulating a unidirectional effect of corticosteroids on nicotine's actions (e.g. decreased sensitivity) must be revised to take into account interacting variables such as the specific nicotine effect being studied and whether that effect normally exhibits tolerance or sensitization. Finally, research is presented which indicates that the corticosterone-elevating effects of nicotine, previously reported for experimenter-administered drug, are also produced when nicotine administration is contingent on an operant response, and at a dose which sustains the development of nicotine self-administration in rats. These findings highlight the feasibility of using self-administration models in future explorations of the relationship between adrenal steroids and nicotine function.

Adrenal Cortex Hormones↗

PubMed1998

Pseudorabies virus-induced leukocyte trafficking into the rat central nervous system.

When the swine alphaherpesvirus pseudorabies virus (PRV) infects the rat retina, it replicates in retinal ganglion cells and invades the central nervous system (CNS) via anterograde transynaptic spread through axons in the optic nerve. Virus can also spread to the CNS via retrograde transport through the oculomotor nucleus that innervates extraocular muscles of the eye. Since retrograde infection of the CNS precedes anterograde transynaptic infection, the temporal sequence of infection of the CNS depends on the route of invasion. Thus, motor neurons are infected first (retrograde infection), followed by CNS neurons innervated by the optic nerve (anterograde transynaptic infection). This temporal separation in the appearance of virus in separate groups of neurons enabled us to compare the immune responses to different stages of CNS infection in the same animal. The data revealed focal trafficking of peripheral immune cells into areas of the CNS infected by retrograde or anterograde transport after PRV Becker was injected into the vitreous body of the eye. Cells expressing the leukocyte common antigen, CD45(+), entered the area of infection from local capillaries prior to any overt expression of neuropathology, and quantitative analysis demonstrated that the number of cells increased in proportion to the number of infected neurons within a given region. Recruitment of cells of monocyte/macrophage lineage began prior to the appearance of CD8(+) cytotoxic lymphocytes, which were, in turn, followed by CD4(+) lymphocytes. These data demonstrate that PRV replication in CNS neurons stimulates the focal infiltration of specific classes of CD45(+) cells in a time-dependent, temporally organized fashion that is correlated directly with the number of infected neurons and the time that a given region has been infected.

Animals↗

PubMed1998

Inverse relationship between fenfluramine-induced prolactin release and blood pressure in humans.

Although substantial evidence from experimental animals suggests that augmentation and reduction in serotonergic neurotransmission both affect arterial blood pressure (BP), it is unknown whether "tonic" central serotonergic activity is related to resting BP variability in humans. We tested this hypothesis in a community sample by evaluating the relationship between resting BP and a neuropharmacologic index of brain serotonergic activity (the fenfluramine challenge test). Subjects were 270 generally healthy men and women aged 25 to 60 years who were not receiving prescribed antihypertensive or psychotropic medications. The sample included 216 non-Hispanic whites and 47 blacks. Resting systolic BP ranged from 85 to 161 mm Hg and diastolic from 58 to 98 mm Hg. Each subject received 0.55 to 0.65 mg/kg D,L-fenfluramine hydrochloride, and the plasma prolactin concentration was measured over 3.5 hours. Analyses revealed a linear, inverse relationship between the maximum fenfluramine-induced prolactin rise and systolic and diastolic BP in whites: r=-0.36 and r=-0.29, respectively (P<0.001 for both). These relationships were not observed in the black participants. In whites, the prolactin response to fenfluramine remained a significant predictor of systolic and diastolic BPs in multivariate models including age, gender, body mass index, physical activity, smoking, and alcohol consumption (P</=0.001). When compared with subjects in the highest quartile of prolactin response, individuals whose prolactin responses to fenfluramine comprised the lowest quartile were 2.6 times more likely to have a resting systolic/diastolic BP of >135/85 mm Hg. These data reveal that in white but not black adults, fenfluramine-induced prolactin release correlates inversely with BP and may indicate a role of central serotonergic activity in the pathogenesis of hypertension.

Adult↗

PubMed1997

Impact of corticotropin-releasing hormone on extracellular norepinephrine in prefrontal cortex after chronic cold stress.

We have previously demonstrated that exposing rats to cold (5 degrees C) for 3-4 weeks potentiates the increase in extracellular norepinephrine (NE) in the medial prefrontal cortex produced by acute tail shock. In the present study, we used microdialysis to determine the duration of cold exposure required to produce this sensitization and explored the mechanism of the phenomenon. Tail shock elicited a twofold greater increase in extracellular NE in the medial prefrontal cortex of rats exposed to cold for 2 weeks than in naive control rats or in rats exposed to cold for 1 week and tested either immediately or after a 2-week delay. Local infusion of 10 microM D-amphetamine or 30 mM K+ increased extracellular NE in the medial prefrontal cortex (approximately 350 and 190%, respectively) comparably in control rats and rats exposed to cold for 3 weeks. In contrast, intraventricular administration of 3.0 microg of corticotropin-releasing hormone increased extracellular NE in the medial prefrontal cortex by 65% in rats exposed to cold for 2 weeks, but only 35% in control rats. These results indicate that an enhanced responsiveness of noradrenergic neurons to acute tail shock (1) requires approximately 2 weeks of cold exposure to develop and (2) may be mediated by a change at the level of the noradrenergic cell bodies rather than the nerve terminals.

Adrenergic Agents↗

PubMed1997

Blood pressure regulation in baroreceptor-denervated rats.

1. Arterial baroreceptor denervation produces acute hypertension, but chronically denervated animals have an average arterial pressure that is similar to that of baroreceptor intact animals. 2. Although cardiopulmonary baroreceptors and renal compensations have been suggested to mediate the restoration of a normal average arterial pressure in sino-aortic denervated rats, such mechanisms are inconsistent with the available data. 3. At present the processes involved in the restoration and long-term maintenance of a normal average arterial pressure in chronic baroreceptor denervated animals are not known. An understanding of the regulation of arterial pressure that occurs in the absence of arterial baroreceptor reflexes may provide important new insights into the mechanisms underlying the long-term regulation of arterial pressure.

Animals↗

PubMed1997

The kidneys stimulate vasopressin release during hemorrhage in rats with chronic NTS lesions.

Elimination of baroreceptor afferent input to the brain produced by chronic lesion of nucleus of the solitary tract (NTS) does not alter vasopressin (VP) release during hypotensive hemorrhage in conscious rats. To investigate whether the kidneys play a critical role in stimulating VP release during hemorrhage in chronic NTS-lesioned rats, we examined the effects of removing potential signals arising from the kidneys. In NTS-lesioned rats, nephrectomy or renal denervation, but not captopril injection, markedly attenuated (but did not abolish) hemorrhage-induced VP release. In contrast, none of these manipulations attenuated the VP response in NTS-intact rats. Hemorrhage increased plasma renin activity in control and NTS-lesioned rats, and this response was not altered by renal denervation. In rats with NTS lesions and renal denervation, hemorrhage induced the expression of Fos in hypothalamic magnocellular VP neurons in a pattern similar to that of hemorrhage in intact rats. Collectively, these results indicate that in chronic NTS-lesioned rats an afferent signal arising from the kidneys stimulates VP release during hemorrhage, possibly through renal nerves. However, with the NTS intact or after the selective removal of arterial baroreceptor inputs, such a role for the kidneys is not apparent. Furthermore, in the absence of the NTS and renal nerves, another signal generated by hypotensive hemorrhage continues to stimulate VP neurons.

Animals↗

PubMed1997

Tonic glutamate-mediated control of rostral ventrolateral medulla and sympathetic vasomotor tone.

Sympathoexcitatory neurons in the rostral ventrolateral medulla (RVLM) play a key role in the tonic maintenance of resting arterial pressure. Removal of tonically active inhibitory inputs to the RVLM provided by the caudal ventrolateral medulla (CVLM) elicits a large increase in arterial pressure. The present study addresses the hypothesis that excitatory amino acids (EAA) provide the excitation of the RVLM responsible for the increase in arterial pressure that occurs after withdrawal of CVLM-mediated inhibition of the RVLM. In rats anesthetized with either alpha-chloralose or urethan, inhibition of the CVLM by local injection of muscimol markedly elevated arterial pressure. Subsequent injection of the EAA receptor antagonist kynurenic acid into the RVLM caused arterial pressure to fall to levels comparable to those that occur-with total autonomic blockade. In contrast, injection of kynurenic acid into the RVLM of control rats had little effect on arterial pressure. These results indicate that the large increase in arterial pressure produced by inhibition of the CVLM is mediated by EAA excitation of RVLM neurons. Furthermore, these data suggest that EAA play a prominent role in the tonic excitation of RVLM neurons, but, in intact rats, inhibition of EAA in the RVLM elicits no change in arterial pressure because of removal of inhibitory as well as excitatory drives of the RVLM.

Animals↗

PubMed1997

Decreases in arterial pressure activate oxytocin neurons in conscious rats.

Hemorrhage and nonhypotensive hypovolemia are known to increase plasma levels of oxytocin (OT) and vasopressin (VP) in rats. The present experiments demonstrated that secretion of OT and VP also are stimulated by acute drug-induced hypotension. Injection of hydralazine abruptly decreased arterial blood pressure in conscious rats and induced Fos expression, a marker of neuronal activation, within OT and VP neurons in the hypothalamus. Hydralazine also elicited substantial increases in plasma levels of both OT and VP. Injection of chlorisondamine similarly elicited acute hypotension and increased plasma levels of OT and VP. Furthermore, when the hypotensive effect of chlorisondamine was blunted by coinfusion of phenylephrine, the induced increases in OT and VP were markedly attenuated. Across all treatments, arterial blood pressure was inversely related to plasma levels of OT and VP. Plasma osmolality was not increased by hydralazine, nor was there evidence of gastric malaise, two known stimuli for OT secretion in rats. These results suggest that arterial hypotension increases neurohypophysial release of OT and VP in conscious rats.

Animals↗

PubMed1997

Influence of GABA in the nucleus of the solitary tract on blood pressure in baroreceptor-denervated rats.

We have previously reported that inhibition of the nucleus of the solitary tract (NTS) in chronically sinoaortic baroreceptor-denervated (SAD) rats has no effect on blood pressure in contrast to the marked increase in blood pressure it elicits in baroreceptor-intact rats. This could result either from a lack of tonic excitatory input to this region or from overriding inhibition of NTS neurons involved in the control of blood pressure. The present study aimed to distinguish between these two possibilities by examining the changes in blood pressure elicited by injection of bicuculline (Bic), a gamma-aminobutyric acid (GABA) antagonist, into the NTS of SAD and control rats. In chloralose-anesthetized baroreceptor-intact rats or acutely SAD rats, injection of 10 pmol Bic into the NTS elicited minimal changes in blood pressure. In contrast, in chronic SAD rats injection of Bic into the NTS elicited a large decrease in blood pressure. The maximal decrease in blood pressure elicited by Bic in chronic SAD rats was equivalent to the maximal decrease in blood pressure that could be evoked by direct excitation of the NTS with L-glutamate. These results suggest that the lack of a tonic role of the NTS in the regulation of blood pressure in chronic SAD rats is a result of maximal GABA-mediated inhibition of relevant NTS neurons.

Animals↗

PubMed1997

Adrenal epinephrine and norepinephrine release to hypoglycemia measured by microdialysis in conscious rats.

Experiments were conducted in conscious male rats to determine whether hypoglycemia induced by insulin administration preferentially stimulated epinephrine (Epi) or norepinephrine (NE) adrenal medullary chromaffin cells. The release of Epi and NE from the adrenal medulla was continuously monitored using a microdialysis probe of novel design that had been inserted in the adrenal medulla approximately 16 h before the administration of insulin. Following insulin, 3 U/kg i.v., blood glucose declined and dialysate Epi levels rose. No measurable increment in dialysate NE was obtained. Similarly, plasma Epi increased with no detectable change in NE. Patterns of dialysate and plasma catecholamine changes were similar in two groups of animals that had been fed or fasted overnight before insulin treatment. However, the magnitude of the Epi increase was greater in the fasted animals. After recovery of the blood glucose concentration to preinsulin levels, dialysate and plasma catecholamine concentrations returned to control values. These experiments clearly demonstrate that adrenal medullary chromaffin cells that produce Epi are preferentially stimulated in response to insulin-induced hypoglycemia.

Adrenal Medulla↗

PubMed1996

Increased neostriatal tyrosine hydroxylation during stress: role of extracellular dopamine and excitatory amino acids.

We examined the regulation of neostriatal tyrosine hydroxylation during acute stress, testing the hypothesis that excitatory amino acids (EAAs) contribute to the stress-evoked increase in dopamine (DA) synthesis. Dialysis probes implanted into neostriatum permitted delivery of drugs and sampling of extracellular fluid. Rats were exposed to 30 min of intermittent tail shock during infusion of an inhibitor of aromatic amino acid decarboxylase (AAAD), NSD-1015 (100 microM), and DOPA was measured in the dialysate. Tail shock was applied beginning either 15 min after the onset of NSD-1015 treatment (the initial rate of DOPA accumulation) or 75 min after the onset of treatment (when DOPA had approached steady state). Tail shock increased the steady-state levels of extracellular DOPA in neostriatum (+40%). However, there was no change in the initial rate of DOPA accumulation unless animals also received the D2 receptor antagonist eticlopride (50 nM), in which case an increase was observed (+228%). The impact of tail shock on the steady-state level of DOPA was attenuated by the D2 agonist quinpirole (100 microM), or by 2-amino-5-phosphonovalerate (APV) (100 microM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (100 microM), EAA antagonists acting at NMDA or D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA) receptors, respectively. These data suggest that acute stress normally has little effect on tyrosine hydroxylation in neostriatum due to the inhibitory influence of DA in the extracellular fluid. However, when that influence is absent (e.g., during extended inhibition of DOPA decarboxylation or blockade of DA receptors), stress increases tyrosine hydroxylation via EAAs acting on NMDA and AMPA receptors. Thus, EAAs released from corticostriatal projections may stimulate DA synthesis and thereby restore dopaminergic activity under conditions in which the availability of DA for release has been compromised.

Administration, Topical↗

PubMed1996

Blockade of angiotensin receptors in rat rostral ventrolateral medulla removes excitatory vasomotor tone.

The rostral ventrolateral medulla (RVLM) plays a primary role in the tonic and phasic control of arterial blood pressure. Stimulation of angiotensin receptors in this region appears to contribute to the tonic excitatory drive of RVLM neurons involved in the control of blood pressure, but the extent of this contribution has not been previously evaluated. The present study used bilateral microinjections of angiotensin receptor antagonists into the RVLM of chloralose-anesthetized rats to determine the degree to which tonic blood pressure was dependent upon this angiotensin-mediated input. Bilateral injection into the RVLM of 1 nmol of [Sar1, Thr8]angiotensin II or [Sar1, Ile8] angiotensin II decreased blood pressure approximately 40 mmHg. The decrease in blood pressure elicited by these angiotensin antagonists was nearly as great as that elicited by complete bilateral inhibition of the RVLM produced by local injections of muscimol or elicited by inhibition of the autonomic nervous system by intravenous injection of chlorisondamine. The decrease in blood pressure caused by injection of these angiotensin antagonists was localized to the RVLM and was dose related. Responses elicited by [Sar1, Thr8]angiotensin II were eliminated by coinjection of angiotensin. In addition to markedly decreasing resting blood pressure, 1 nmol of [Sar1, Thr8]angiotensin II injected into the RVLM, also completely antagonized the increase in blood pressure elicited by blocking the tonic inhibitory influence exerted on the RVLM by neurons in the caudal ventrolateral medulla. These results demonstrate that tonic stimulation of angiotensin receptors in the RVLM accounts for much of the excitatory sympathetic vasomotor drive emanating from the RVLM.

1-Sarcosine-8-Isoleucine Angiotensin II↗

PubMed1996

Role of gamma-aminobutyric acid B receptors in baroreceptor reflexes in hypertensive rats.

Previous studies demonstrated that stimulation of gamma-aminobutyric acid B (GABA(B)) receptors in the nucleus tractus solitarius of spontaneously hypertensive rats (SHR) elicited a larger increase in arterial pressure compared with control Wistar-Kyoto rats. Since stimulation of GABA(B) receptors in the nucleus tractus solitarius attenuates cardiovascular responses evoked by electrical stimulation of the aortic depressor nerve in normotensive rats and there is evidence of a central neural attenuation of aortic depressor nerve-evoked responses in SHR, we conducted studies to test the hypothesis that enhanced stimulation of GABA(B) receptors in the nucleus tractus solitarius in SHR is responsible for the attenuation of the aortic depressor nerve-evoked responses. Electrical stimulation of the left aortic depressor nerve resulted in frequency-dependent decreases in arterial pressure, heart rate, and splanchnic sympathetic nerve activity in urethane-anesthetized control rats. These responses were not significantly altered by injection of the GABA(B) receptor antagonist CGP 35348 into the ipsilateral nucleus tractus solitarius. The responses evoked by aortic depressor nerve stimulation were attenuated in SHR. This attenuation was particularly apparent with more prolonged periods (>15 seconds) of high-frequency (25-Hz) stimulation, with the depressor and sympathetic nerve responses diminishing during the course of stimulation. This time- and frequency-dependent attenuation of baroreceptor-evoked depressor responses was reversed by injection of CGP 35348 into the ipsilateral nucleus tractus solitarius. Rats made hypertensive by treatment with deoxycorticosterone plus salt did not have attenuated aortic depressor nerve-evoked responses. These results suggest that alterations in GABA b-mediated neural transmission in the nucleus tractus solitarius contribute to the attenuation of the baroreceptor reflex observed in SHR.

Animals↗

PubMed1995

c-Fos expression in brain in response to hypotension and hypertension in conscious rats.

Hypotension- and hypertension-evoked expression of the protein product, Fos, of the immediate early gene c-fos was assessed throughout the rat brain as an approach for describing the neuronal populations that respond to alterations in arterial blood pressure. Conscious, chronically catheterized rats were treated with the vasoconstricting drug phenylephrine or the vasodilatating drug hydralazine to increase or decrease, respectively, arterial pressure by approx. 40 mm Hg for 90 min. Rats were then anesthetized, fixed by vascular perfusion, and sections representing the entire brain were processed for the immunocytochemical localization of Fos. In control rats treated with isotonic saline, few Fos-positive neurons were observed. In contrast, phenylephrine and hydralazine treatments resulted in different, yet reproducible, patterns of Fos expression in the brain, with hydralazine evoking Fos expression in more brain regions than phenylephrine. Brain regions containing Fos-positive neurons in rats treated with hydralazine included nucleus tractus solitarius, area postrema, caudal ventrolateral medulla, rostral ventrolateral medulla, bed nucleus of the stria terminalis, amygdala, paraventricular nucleus, supraoptic nucleus, subfornical organ and the Islands of Calleja. The nucleus tractus solitarius, paraventricular nucleus and the amygdala also contained Fos-positive neurons in phenylephrine-treated rats, although the number of Fos-positive neurons was always less than that noted in the hydralazine-treated rats and the location of Fos-positive neurons within these regions tended to differ between treatments. These results generally fit within an emerging understanding of brain circuitry underlying cardiovascular regulation.

Animals↗