Inhibition of catecholamine (noradrenaline,dopamine) release in the locus coeruleus and the hypothalamus by baroreceptor activation: identification of the involved baroreceptors

We have previously shown that experimentally induced blood pressure changes modify the release rates of catecholamines in the hypothalamus and the locus coeruleus. The aim of the present investigation was to identify the peripheral baroreceptors and the centripetal pathways responsible for the changes of catecholamine release in these brain areas.In anaesthetized cats, push-pull cannulae were bilaterally inserted into the locus coeruleus and the posterior hypothalamus. The two brain areas were superfused simultaneously with artificial cerebrospinal fluid. Baroreceptor activation by phenylephrine-induced blood pressure elevation decreased the release rate of noradrenaline in the locus coeruleus and the release rates of noradrenaline and dopamine in the posterior hypothalamus. Similar effects were elicited by electrical stimulation of the central trunk of the transected vagus and aortic depressor nerves (vagus-ADN). Transection of the nerves abolished the effect of phenylephrine on the release of noradrenaline in the locus coeruleus. Nerve transections attenuated slightly the decreased release of noradrenaline elicited by phenylephrine in the posterior hypothalamus, while the reduced dopamine release rate was not influenced. The selective stimulation of baroreceptors in the carotid sinus by an inflatable catheter did not influence the release of catecholamines in the locus coeruleus, while release rates of noradrenaline and dopamine in the posterior hypothalamus were decreased.The simultaneous superfusion of locus coeruleus and hypothalamus revealed that, in both areas, noradrenaline release is inhibited by baroreceptor activation. Noradrenergic neurons of the posterior hypothalamus are inhibited by baroreceptor impulses conducted by the carotid sinus nerve and vagus-ADN, while the noradrenergic neurons of the locus coeruleus seem to respond to impulses transmitted by vagus-ADN. Furthermore, baroreceptor activation inhibits dopaminergic neurons in the hypothalamus but not in the locus coeruleus.     

药物和血流动力学改变对大鼠下丘脑后部氨基酸神经递质释放的影响

应用推挽灌流技术，研究清醒，自由活动大鼠下丘脑后部内源性氨基酸神经递质γ－氨基丁酸（ＧＡＢＡ），牛磺酸（Ｔａｕ），谷氨酸（Ｇｌｕ）和５－羟色胺（５－ＨＴ）的释放，观察某些影响神经元活动的药物和改变外周血流动力学时对它们释放的影响。结果表明，在正常条件下。连续观察６ｈ．其基础释放相对恒定，用高Ｋ＋（５０．９０ｍｍｏｌ·Ｌ－１）人工脑脊液灌流。释放依剂量增加，藜芦定碱（１，１０μｍｏｌ·Ｌ－１）有类似作用；河豚毒素（１μｍｏｌ·Ｌ－１）可使ＣＡ８Ａ，Ｔａｕ和５－ＨＴ释放减少，对Ｇｌｕ的释放影响较弱。外周血流动力学改变对ＧＡＢＡ。Ｔａｕ和Ｇｌｕ的释放均可产生明显的影响。血管阻力和血容量增加血压上升时。ＧＡＢＡ。Ｔａｕ和Ｇｌｕ释放明显增加：血管扩张和血容量减少时。ＧＡＢＡ。Ｔａｕ的释放减少。而Ｇｌｕ的释放则增加。结果提示。下丘脑后部ＣＡＢＡ，Ｔａｕ和Ｇｌｕ作为神经递质。可能参与外周动脉血压的调节．     

Release of endogenous GABA in the posterior hypothalamus of the conscious rat; effects of drugs and experimentally induced blood pressure changes

Summary Push-pull superfusion was used to investigate the release of endogenous GABA in the posterior hypothalamus of the conscious, freely moving rat at basal conditions and in response to centrally applied drugs or to peripherally induced blood pressure changes.After an initial, exponential decline, the release rate of GABA remained fairly constant for many hours. Fluctuations in the release rate of GABA point to the existence of an ultradian rhythm with an approximate frequency of 1 cycle/65 min. Hypothalamic superfusion with a potassium-rich (50 or 90 mmol/1) artificial cerebrospinal fluid led to a concentration-dependent increase in the GABA release. The release of GABA was also enhanced by veratridine (1 or 10 mol/1) in a concentration-dependent way. Hypothalamic superfusion with the neutrotoxin tetrodotoxin (1 gmmol/1) led to a long-lasting decrease in the GABA release. The rise in blood pressure (45 mmHg) elicited by an intravenous infusion of noradrenaline was associated with an increased release rate of GABA in the hypothalamus. Hypotension produced by nitroprusside (25 mmHg) led to a counteracting decrease in hypothalamic GABA outflow.The findings suggest that approximately 4510 of the basal outflow of GABA found in the superfusate are released from GABA-ergic neurons of the posterior hypothalamus. The release rate of GABA fluctuates according to an ultradian rhythm. The modified release of GABA in response to experimentally induced blood pressure changes suggests that, in the posterior hypothalamus of the conscious rat, GABAergic neurons are involved in cardiovascular control and possess a hypotensive function.This work was supported by the Fonds zur Förderung der wissenschaftlichen ForschungCorrespondence to N. Singewald at the above address     

Ionic and haemodynamic changes influence the release of the excitatory amino acid glutamate in the posterior hypothalamus

The push-pull technique was used to investigate the release of the excitatory amino acid glutamate in the posterior hypothalamic area of the conscious rat. The hypothalamus was superfused through the pushpull cannula with artificial cerebrospinal fluid (CSF), and the superfusate was collected in time periods of 10 min when ionic conditions in the CSF were changed, or in short periods of 3 min when blood pressure changes were evoked. The mean glutamate release rate was 2.8 + 0.7 pmol/min. Depolarization by hypothalamic superfusion with CSF containing 50 mM K⁺ enhanced the release of glutamate in the presence of Ca²⁺. The K⁺-induced release was attenuated by 40% when the hypothalamus was superfused with Ca²⁺-free CSF. Replacement of Ca²⁺ by Mg²⁺ abolished the K⁺-induced release of glutamate. Hypovolaemia elicited by haemorrhage enhanced the release rate of glutamate. Similarly, a hypotension elicited by i.v. injection of chlorisondamine (3 mg/kg) led to a pronounced and permanent enhancement in glutamate release. The effects of hypovolaemia and chlorisondamine on glutamate release were abolished in aortic denervated rats, indicating that this response is due to a decrease of impulse generation in baroreceptors. A hypovolaemia elicited by blood infusion did not affect the release of glutamate. Similarly, a pronounced pressor response to phenylephrine (15 /kg per minute) infused intravenously for 9 min was ineffective.The results show that the K⁺-induced release of glutamate in the hypothalamus is dependent on the presence of Ca²⁺. The increase in glutamate release rate by hypovolaemia or chlorisondamine suggests that the glutamatergic neurons in the posterior hypothalamic area respond to unloading of aortic baroreceptors and possess a counteracting, hypertensive function.     

Effects of inescapable shock and conditioned fear on the release of excitatory and inhibitory amino acids in the locus coeruleus

We investigated the importance of endogenous amino acids in the locus coeruleus in inescapable electric shock and conditioned fear. In naive rats and in rats exposed to noise (N), light (L) and electric shock (S) or to N + L only, the locus coeruleus was superfused with artificial cerebrospinal fluid through a push-pull cannula and the release of GABA, taurine, glutamate, aspartate, serine and glutamine was determined in the superfusate by HPLC after derivatization with o-phthaldialdehyde. Locomotor activity, arterial blood pressure and heart rate were telemetrically monitored. The placement of naive rats or conditioned rats from their home cage to a chamber provided with a grid-floor for shock virtually did not change the release rates of the amino acids in the locus coeruleus. Motility was enhanced in naive and conditioned rats to a similar extent. Blood pressure and heart rate were enhanced in conditioned rats only. Exposure to N + L + S for 5 min greatly enhanced the release rates of all determined amino acids in the locus coeruleus. In conditioned rats the increase in release of most amino acids lasted longer than in naive rats. Electric shock also enhanced motility, blood pressure and heart rate. In conditioned rats, motility and cardiovascular changes were more pronounced and/or lasted longer than in naive rats. Exposure of conditioned rats to the conditioned stimuli N + L for 5 min led to an increased release of taurine and aspartate. The enhanced release of taurine lasted 30 min. Exposure to N + L did not affect the release rates of amino acids in naive rats. N + L did not influence motility but arterial blood pressure and heart rate were elevated in conditioned rats. The findings show that inescapable electric shock enhances the release of several amino acids in the locus coeruleus, while conditioned fear selectively increases the outflow of taurine and aspartate. Moreover, conditioned fear prolongs the response of excitatory and inhibitory amino acids to electric shock. The results suggest that an excitatory amino acid (aspartate) and an inhibitory amino acid (taurine) of the locus coeruleus are implicated in conditioned fear.     

Additive Role of the Vestibular End Organ and Baroreceptors on the Regulation of Blood Pressure in Rats

Contribution of the vestibular end organ to regulation of arterial pressure was quantitatively compared with the role of baroreceptors in terms of baroreflex sensitivity and c-Fos protein expression in the rostral ventrolateral medulla (RVLM). Baroreflex sensitivity and c-Fos protein expression in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or baroreceptor unloading. BL attenuated baroreflex sensitivity during intravenous infusion of sodium nitroprusside (SNP), but did not significantly affect the sensitivity following infusion of phenylephrine (PE). Baroreflex sensitivity became positive following sinoaortic denervation (SAD) during infusion of PE and attenuated sensitivity during infusion of SNP. Baroreflex sensitivity also became positive following double ablation (BL+SAD) during infusion of PE, and attenuated sensitivity during infusion of SNP. c-Fos protein expression increased significantly in the RVLM in the sham group after SNP administration. However, the BL, SAD, and SAD+BL groups showed significant decreases in c-Fos protein expression compared with that in the sham group. The SAD group showed more reduced c-Fos protein expression than that in the BL group, and the SAD+BL group showed less expression than that in the SAD group. These results suggest that the vestibular system cooperates with baroreceptors to maintain arterial pressure during hypotension but that baroreceptors regulate arterial pressure during both hypotension and hypertension. Additionally, afferent signals for maintaining blood pressure from the vestibular end organs and the baroreceptors may be integrated in the RVLM.     

Aortic baroreceptors exert a tonically active restraining influence on centrally mediated depressor responses.

This study tested the hypothesis that aortic baroreceptors exert a central restraining influence on centrally mediated depressor responses and that this mechanism is tonically active and is independent of their modulation of basal arterial pressure. The effects of short-term (48-72 h) aortic baroreceptor deafferentation (ABD) on the acute hemodynamic (peripherally mediated pressor and centrally mediated depressor) effects of clonidine were investigated in conscious and anesthetized normotensive rats. ABD caused an immediate increase in basal arterial pressure and heart rate and a significant attenuation of the baroreceptor reflex control of heart rate. Since only arterial pressure subsided to control levels by 48-72 h, the data suggest that central reorganizational changes were potent enough to overcome the tonically active restraining influence of aortic baroreceptors on basal arterial pressure but not heart rate. Clonidine produced a similar pressor effect in conscious ABD and sham rats but its depressor effect was significantly greater in ABD rats whose baroreceptor reflex control of heart rate was significantly attenuated. Intracisternal (i.c.) administration of 0.1 microgram of clonidine, a dose that had no effect when administered i.v., produced a near-maximal depressor effect in conscious ABD rats vs. no effect in sham rats (-16.7 +/- 4.1 vs. -0.3 +/- 2 mm Hg; p less than 0.001). The depressor effect of clonidine was also enhanced in chloralose-anesthetized rats and coincided with an anesthesia-induced attenuation of the baroreceptor reflex control of heart rate. It is concluded that aortic baroreceptors exert a potent restraining influence on the centrally mediated depressor effect of clonidine. Since ABD had no significant effect on the depressor response to nitroprusside, but enhanced the depressor response to ganglion blockade by hexamethonium, the data suggest that a higher peripheral sympathetic neural activity existed in ABD rats. The reorganizational changes that occurred within 48-72 h after ABD were potent enough to overcome the tonically active restraining influence of aortic baroreceptors on basal arterial pressure but not on the centrally mediated depressor responses. Thus, the buffering influence of aortic baroreceptors and their central projections on centrally mediated depressor responses seems to be tonically involved in blood pressure control.     

Effects of α-adrenoceptor-stimulating drugs on baroreceptor reflexes in conscious cats

The action of some α-adrenoceptor stimulating drugs with a central effect (clonidine, α-methyldopa, reserpine) on baroreceptor reflexes was studied in conscious cats (both in the resting condition and when influenced by emotional tension or electrical stimulation of the hypothalamus). The sedative effect of these drugs was observed simultaneously with bradycardia and the increase of baroreceptor reflexes. Clonidine and reserpine (in 6–24 h after injection) lowered blood pressure while α-methyldopa (40 mg/kg) increased it. Confrontation with a dog or electrical hypothalamic stimulation produced hypertensive reactions and diminished the baroreflexes. All drugs reduced the emotional and hypertensive reactions caused by natural stress situations and restored baroreceptor reflexes. On the other hand, neither clonidine nor α-methyldopa changed the decrease of baroreceptor reflexes caused by electrical hypothalamic stimulation. It is supposed that central α-adrenoceptor stimulating drugs do not influence processes of hypothalamic modulation of baroreceptor reflexes. The increase in baroreflex activity after clonidine, α-methyldopa and reserpine appears to be due to a direct effect of the drugs on the central neurones mediating baroreceptor reflexes and to the tranquillizing action of these drugs.     

Effects of taurine,homotaurine and GABA on hypothalamic and striatal dopamine metabolism

Summary To elucidate the effects of taurine on hypothalamic and striatal dopaminergic neurotransmission we compared its effects to those of -aminobutyric acid (GABA) and homotaurine (a GABA_A-receptor agonist) on hypothalamic and striatal concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and, in the case of striatum, 3-methoxytyramine (3-MT) in rats. In addition, hypothalamic and striatal 5-hydroxytryptamine (5-HT) und 5-hydroxyindoleacetic acid, hypothalamic noradrenaline (NA) and 3-methoxy-4-hydroxyphenylglycol sulfate, and pituitary DA concentrations were also measured. The amino acids were injected into the lateral brain ventricles of conscious male rats in doses of 10 and 36 mol/rat, and rat were sacrificed 15 and 60 min later, respectively.Homotaurine (by 11010) but not the other two amino acids elevated striatal DA, whereas hypothalamic DA was increased by both taurine (36%) and homotaurine (31%). All three amino acids at 36 mol elevated striatal DOPAC, homotaurine (51%) more than taurine (31%) or GABA (30%), and hypothalamic DOPAC, both taurine (102%) and homotaurine (82%) clearly more than GABA (34%). Neither striatal nor hypothalamic HVA was altered by any of the amino acids. At 10 mol the amino acids decreased striatal 3-MT by about 40%. At 36 mol taurine and homotaurine reduced 3-MT by about 70%, whereas increasing the dose of GABA did not further reduce 3-MT. Both taurine and homotaurine at 36 mol decreased hypothalamic NA content. Neither hypothalamic nor striatal 5-HT metabolism was altered. In the neurointermediate lobe of the pituitary gland taurine at 10 mol but not at 36 mol slightly (20%) increased DA.These results show that taurine and homotaurine clearly alter the hypothalamic DA metabolism, and give further support to the suggestion that taurine and homotaurine similarly to GABA reduce the release of DA in the striatum. Homotaurine seems to alter the striatal DA metabolism more effectively than taurine or GABA. On the other hand, hypothalamic DA seems to be equally sensitive to taurine and homotaurine, and is clearly less sensitive to GABA. The pronounced elevation of hypothalamic DA and DOPAC after taurine and homotaurine could be related to changes in hypothalamic NA. Send offprint requests to L. Ahtee at the above address     

Amino acids injected into the cerebroventricular system induce an enhancement of reflex bradycardia in the rat

The effects of administration of taurine, GABA and glycine, into the lateral cerebral ventricle, on cardiovascular function were assessed in urethane-anaesthetized rats. Intraventricular administration of either taurine (10-30 micrograms), GABA (5-20 micrograms) or glycine (5-20 micrograms) caused a dose-dependent decrease in both the heart rate and the mean arterial pressure. For example, both the heart rate and the mean arterial pressure fell almost immediately and reached their minimum levels about 5 min after an injection of 20 micrograms of taurine. The cardiovascular responses recovered about 30 min after the injection of taurine. Also, reflex bradycardia was produced in the rats by intravenous infusion of adrenaline (1-5 micrograms/kg). Intraventricular pretreatment of the rats with either taurine, GABA or glycine, although causing no change in the adrenaline-induced pressor effect, did enhance the adrenaline-induced reflex bradycardia. However, pretreatment of the rats intravenously with the same dose of taurine, GABA or glycine had no effect on the adrenaline-induced bradycardia. These data indicate that these amino acids act through a central mechanism to facilitate reflex bradycardia mediated through baroceptor reflexes in response to an acute increase in arterial pressure.     

Differential amino acid transmission in the locus coeruleus of Wistar Kyoto and spontaneously hypertensive rats

In addition to differences in their blood pressure, Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) are known to differ in their emotional behaviour. The neurochemistry underlying these differences is not well understood. In the present study the release rates of the two main regulatory amino acids in the locus coeruleus, glutamate and gamma-aminobutyric acid (GABA), were monitored in WKY rats and SHR to investigate whether basal and/or challenged neurotransmission differs between these strains. The strains differed in their basal blood pressure (WKY 102±2 mmHg, SHR 140±4 mmHg), as well as in their emotional behaviour, since WKY rats displayed enhanced anxiety-related behaviour in the open field test (time in centre: WKY 197±40 s/30 min, SHR 741±93 s/30 min). Basal glutamate and GABA release rates did not differ between WKY rats and SHR. A rise in blood pressure induced by intravenous infusion of noradrenaline for 10 min enhanced GABA release in WKY rats by 60%, while no effect was observed in SHR. Glutamate release did not respond to experimental hypertension in both strains. Intravenous infusion of sodium nitroprusside led to a fall in blood pressure, which was less pronounced and was of shorter duration in WKY rats than in SHR. The depressor response had no effect on amino acid release in the locus coeruleus of both strains. Mild stress induced by noise or tail pinch led to slight rises in arterial blood pressure (10 mmHg and 20 mmHg respectively), which were similar in WKY rats and SHR. Tail pinch enhanced the release rates of glutamate and GABA in the locus coeruleus of WKY rats and SHR; however, no strain differences were noted. Noise stress did not significantly influence amino acid release. These findings demonstrate that SHR and WKY rats differ in GABAergic neurotransmission, which is revealed in response to specific cardiovascular challenges, but not to mild stressors. The observed lack of GABA response to blood pressure elevation in SHR may reflect a disturbed mechanism counteracting high blood pressure, possibly contributing to hypertension in this strain.     

Effects of melatonin on blood pressure in stress-induced hypertension in rats

Melatonin, acting through its receptors, is involved in numerous physiological processes, including blood pressure (BP) regulation. In present study, the effect of melatonin inhibition on stress-induced hypertension was investigated. The hypertensive model consisted of male Sprague-Dawley rats subjected to electrical foot-shock combined with noise. Microinjection of melatonin (0.1 and 1.0 mmol/L) into the anterior hypothalamic area (AHA) produced a fall in BP in nomortensive rats and stress-induced hypertensive rats (SIHR). Luzindole (10 mmol/L), a competitive antagonist of melatonin MT1 and MT2 receptors, almost completely abolished the depressor effect of melatonin, the MT2 receptor-specific antagonist 4-phenyl-2-propionamidotetralin (10 mmol/L) partially blocked (by approximately 60%) the depressor effect of melatonin, whereas the MT3 receptor-selective antagonist prazosin (10 mmol/L) failed to antagonize the effects of melatonin. Brain microdialysis was performed in the AHA and the rostral ventrolateral medulla (RVLM). Melatonin and amino acids in the dialysate samples collected were detected by high-performance liquid chromatography combined with fluorescence detection. The results indicated that melatonin concentrations in the AHA were reduced in SIHR. Microinjection of melatonin into the AHA decreased glutamate release and increased GABA and taurine release in the RVLM, which were paralleled by a decrease in arterial pressure. The mRNA expression of MT2 in the AHA of SIHR was higher than that in normotensive control rats, whereas there was no significant difference in MT1 mRNA expressin between the two groups. The results of the present study suggest that both a decrease of melatonin and an increase in the MT2 receptor in the AHA are involved in the manifestation of stress-induced hypertension. Both MT1 and MT2 receptors participated in the antihypertensive effect of melatonin in the AHA. The antihypertensive effect of melatonin was related to the decreases in the excitatory amino acid glutamate and increases in the inhibitory amino acids taurine and GABA in the RVLM.     

Impact of the UV-B filter 4-(Methylbenzylidene)-camphor (4-MBC) during prenatal development in the neuroendocrine regulation of gonadal axis in male and female adult rats

4-(Methylbenzylidene)-camphor (4-MBC), a UV-B ray filter, is an endocrine disruptors (ED). Our goal was to study the effect of 4-MBC on the neuroendocrine parameters that regulate reproduction in adult female and male rats that received this disrupter during prenatal development. The 4-MBC was administered (sc) to female rats (FO) since pregnancy onset, in doses of 100 mg/kg every other day. The litters (F1) were sacrificed at 70 days to determine gonadotrophin serum levels and also GnRH and the amino acids glutamate, aspartate and GABA release from the hypothalamus. The male litter rats (F1) present at adult age a decrease in serum LH and FSH concentration and so also GnRH, excitatory amino acids and GABA hypothalamic secretion. The female litters (F1) rats present at adult age an increase in serum LH and FSH concentration, whereas hypothalamic GnRH release was not modified. In these animals a significant increase of hypothalamic aspartate release as well as GABA secretion decrease were observed. Glutamate secretion was not modified. All these changes were accompanied by an advance (3 days) on the vaginal opening in 4-MBC rats group. In conclusion, prenatal administration of 4-MBC disrupts the gonadal axis in a sexual dimorphic mode that could be connected with the physiological sexual differences in the development of gonadotrophin secretion hypothalamic control mechanisms.     

Resetting of aortic baroreceptors in response to hypotension does not alter gain sensitivity

1. In chronic hypertension, the baroreceptors reset to hypertensive levels with a decrease in gain sensitivity, but only a few studies have evaluated baroreceptor resetting during chronic hypotension and, under these conditions, no consistent information is available concerning changes in baroreceptor gain sensitivity. Therefore, in the present study, the aortic baroreceptor function curve and the baroreflex control of heart rate (HR) were evaluated in chronic hypotension produced by myocardial infarction (MI) with no heart failure. 2. Aortic baroreceptor function curves were studied in anaesthetized three groups of rats: (i) MI-7, six rats 7 days after MI; (ii) MI-30, nine rats 30 days after MI; and (iii) five control animals (SHAM). The pressure-nerve activity relationship was measured during rapid changes in blood pressure by integrating the whole-nerve activity of the baroreceptors in a computerized beat-to-beat analysis. 3. Both long-term periods (7 or 30 days) of hypotension were accompanied by complete resetting of the baroreceptor in rats (the leftward displacement of the baroreceptor curve matched the decrease in blood pressure). Moreover, the resetting of the baroreceptor function curve was not accompanied by changes in gain sensitivity (1.47, 1.64 and 1.67%/mmHg for SHAM, MI-7 and MI-30 groups, respectively) and the baroreflex control of HR was normal comparing SHAM and MI-30 groups (bradycardic 1.62 +/- 0.18 vs 1.99 +/- 0.52 b.p.m./mmHg, respectively; tachycardic 3.6 +/- 0.5 vs 4.1 +/- 0.4 b.p.m./mmHg for, respectively). 4. The data indicate that the resetting of baroreceptors in chronic hypotension is stable and is not accompanied by changes in gain sensitivity, as observed in hypertension. This may account for the normal baroreflex control of HR observed in non-anaesthetized rats.     

Effects of blood pressure changes on the catecholamine release in the locus coeruleus of cats anaesthetized with pentobarbital or chloralose

Summary Effects of carotid occlusion and drugs applied intravenously on the release of endogenous catecholamines in the locus coeruleus of cats anaesthetized with pentobarbital or chloralose were investigated. The locus coeruleus was superfused bilaterally with artificial cerebrospinal fluid through push-pull cannulae inserted stereotaxically. Dopamine, noradrenaline and in some experiments also adrenaline were determined radioenzymatically in the superfusate.Under pentobarbital anaesthesia, a bilateral carotid occlusion increased the release rate of noradrenaline in the locus coeruleus, while the release of dopamine was decreased. These changes were due to the fall of blood pressure in the carotid sinus caused by the occlusion. Loading of baroreceptors by elevating blood pressure with phenylephrine (10 g·kg^–1·min^–1, i.v. infusion) was accompanied by a decreased release of noradrenaline in the locus coeruleus. This decrease in noradrenaline release was not detected in the caudal aspect of the locus coeruleus. Under chloralose anaesthesia, phenylephrine diminished the release rate of noradrenaline to about the same extent as under pentobarbital anaesthesia. The release rate of adrenaline was also decreased. A prolonged infusion of phenylephrine led to a prolonged pressor response associated with a sustained decrease in the noradrenaline release rate. Intravenous injection of chlorisondamine (3 mg·kg^–1) did not change the release of noradrenaline, while dopamine release was reduced.It is concluded that the release of catecholamines in the locus coeruleus is influenced by signals originating from peripheral baroreceptors. The influences are similar under pentobarbital and chloralose anaesthesia. Noradrenergic neurons responding to haemodynamic signals are not uniformly distributed within the locus coeruleus. It is suggested that noradrenergic and possibly dopaminergic and adrenergic neurons of the locus coeruleus are involved in the baroreceptor reflex, thus contributing to central homeostasis of blood pressure.     

Effect of propranolol on central neurotransmitter release in Wistar rats analysed by brain microdialysis

1. The effect of propranolol on amino acid neurotransmitter release in the rostral ventrolateral medulla (RVLM) was examined in urethane-anaesthetized male Wistar rats. 2. Amino acids released in the RVLM in response to intravenous administration of propranolol (0.4 mg/kg per min; n = 6) or nitroglycerin (0.02 mg/kg per min; n = 5) were determined by the brain microdialysis method. 3. Amino acids in dialysates were analysed by high-performance liquid chromatography and were quantified by ultraviolet absorbance. 4. Administration of both intravenous propranolol and nitroglycerin significantly decreased arterial blood pressure. Heart rate was decreased only by propranolol. 5. The reduction in arterial blood pressure produced by intravenous propranolol was accompanied by a decrease in the release of the excitatory amino acid glutamate in the RVLM. 6. The reduction in arterial blood pressure following intravenous nitroglycerin was not accompanied by a release of glutamate. 7. There were no significant changes in the levels of other amino acids (glycine, taurine, GABA) following either propranolol or nitroglycerin. 8. The decrease in glutamate release in the RVLM may account, in part, for the central depressor mechanism of propranolol.     

Captopril and the maintenance of blood pressure after sinoaortic denervation in the rabbit.

1. At a dose of 1 mg/kg intravenously, captopril lowered blood pressure in conscious rabbits, that had undergone denervation of sinoaortic baroreceptors, but had no effect on heart rate. In sham-operated controls, this dose caused only an increase in heart rate. 2. In the same experiments, captopril caused a substantial inhibition of plasma angiotensin converting enzyme (CE) activity of rapid onset and gradual decline over 2 to 3 h. The time course of recovery of blood pressure and plasma CE activity were similar. 3. Saralasin, by intravenous infusion, lowered blood pressure in sinoaortic rabbits but to a smaller extent than captopril. 4. The fall in blood pressure observed after captopril is not dependent on the integrity of baroreceptor afferents.     

Analysis of the Baroreceptor and Vestibular Receptor Inputs in the Rostral Ventrolateral Medulla following Hypotension in Conscious Rats

Input signals originating from baroreceptors and vestibular receptors are integrated in the rostral ventrolateral medulla (RVLM) to maintain blood pressure during postural movement. The contribution of baroreceptors and vestibular receptors in the maintenance of blood pressure following hypotension were quantitatively analyzed by measuring phosphorylated extracellular regulated protein kinase (pERK) expression and glutamate release in the RVLM. The expression of pERK and glutamate release in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or sinoaortic denervation (SAD) following hypotension induced by a sodium nitroprusside (SNP) infusion. The expression of pERK was significantly increased in the RVLM in the control group following SNP infusion, and expression peaked 10 min after SNP infusion. The number of pERK positive neurons increased following SNP infusion in BL, SAD, and BL+SAD groups, although the increase was smaller than seen in the control group. The SAD group showed a relatively higher reduction in pERK expression when compared with the BL group. The level of glutamate release was significantly increased in the RVLM in control, BL, SAD groups following SNP infusion, and this peaked 10 min after SNP infusion. The SAD group showed a relatively higher reduction in glutamate release when compared with the BL group. These results suggest that the baroreceptors are more powerful in pERK expression and glutamate release in the RVLM following hypotension than the vestibular receptors, but the vestibular receptors still have an important role in the RVLM.     

Role of taurine as a possible transmitter in the thermoregulatory pathways of the rat.

Taurine (10 and 20 micrograms) injected unilaterally into the lateral ventricle of rats caused an increase in core temperature. Bilateral injection of taurine 2.5 and 5 micrograms into the preoptic region of the anterior hypothalamus induced a dose-related hyperthermia: higher doses (10 micrograms) caused hypothermia. Intrahypothalamically taurine-induced hyperthermia was blocked by prior injection of strychnine hydrochloride (5 and 15 micrograms); doses which alone had no effect on core temperature. Of the other inhibitory amino acids injected intrahypothalamically hypotaurine also induced a hyperthermia. GABA (10 micrograms) caused hypothermia; glycine (10 micrograms) had no effect. Potassium (50 mM) stimulated release of radioactivity from superfused slices of anterior hypothalamus prelabelled with [3H]taurine in a calcium-dependent manner. A high affinity uptake mechanism with a Km of 8.5 microM was demonstrated with [3H]taurine into slices of anterior hypothalamus. Taurine may have a neurotransmitter role in the anterior hypothalamus but whether the body temperature effects represent physiological or pharmacological events remains to be established.     

Blood pressure and hypothalamic NA-GABA interaction in spontaneously hypertensive rats (SHR): effect of administration DSP-4

The effect of DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] on the content of catecholamines (NA and DA) and gamma-aminobutyric acid (GABA) in the hypothalamus and on the blood pressure were studied in rats. Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were injected with DSP-4 (50 mg/kg i.p. twice) and tested for 15 days thereafter. Fifteen days after DSP-4 lesioning, a significant reduction of NA levels without changes in DA and GABA concentration in the hypothalamus of both strains was found. However the blood pressure appeared unaffected by the DSP-4 pretreatment in WKY and SHR rats. In line with previous data the amounts of catecholamines and GABA in the hypothalamus were significantly lower in SHR control animals than in WKY control rats. The results suggest that NA/GABA interaction in the hypothalamus do not play an important role in blood pressure regulation. It may be further supposed that the local NA transmission does not play an important role in the phenomenon discussed. Moreover, a contribution of hypothalamic GABA and DA to the control of blood pressure is confirmed.