HISTAMINE IN THE POSTERODORSAL MEDIAL AMYGDALA MODULATES CARDIOVASCULAR REFLEX RESPONSES IN AWAKE RATS

Centrally injected histamine (HA) affects heart rate (HR), arterial blood pressure (BP), and sympathetic activity in rats. The posterodorsal medial amygdala (MePD) has high levels of histidine decarboxylase, connections with brain areas involved with the modulation of cardiovascular responses, and is relevant for the pathogenesis of hypertension. However, there is no report demonstrating the role of the MePD histaminergic activity on the cardiovascular function in awake rats. The alms of the present work were: 1) to study the effects of two doses (10-100 nM) of HA microinjected in the MePD on basal cardiovascular recordings and on baroreflex- and chemoreflex-mediated responses; 2) to reveal whether cardiovascular reflex responses could be affected by MePD microinjections of (R)-alpha-methylhistamine (AH(3)), an agonist of the inhibitory autoreceptor H(3); and, 3) to carry out a power spectral analysis to evaluate the contribution of the sympathetic and parasympathetic components in the variability of the HR and BP recordings. When compared with the control group (microinjected with saline, 0.3 mu l), HA (10 nM) promoted an increase in the MAP(50), i.e. the mean value of BP at half of the HR range evoked by the baroreflex response. Histamine (100 nM) did not affect the baroreflex activity, but significantly decreased the parasympathetic component of the HR variability, increased the sympathetic/parasympathetic balance at basal conditions (these two latter evaluated by the power spectral analysis), and promoted an impairment in the chemoreflex bradycardic response. Microinjection of AH(3) (10 mu M) led to mixed results, which resembled the effects of both doses of HA employed here. Present data suggest that cardiovascular changes induced by baroreceptors and chemoreceptors involve the histaminergic activity in the MePD. This neural regulation of reflex cardiovascular responses can have important implications for homeostatic and allostatic conditions and possibly for the behavioral displays modulated by the rat MePD. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

[Anesthesia management in implantation of baroreceptor stimulators].

Baroreceptor stimulators are novel implantable devices that activate the carotid baroreceptor reflex. This results in a decrease in activity of the sympathetic nervous system and inhibition of the renin-angiotensin-aldosterone system. In patients with drug-resistant hypertension, permanent electrical activation of the baroreceptor reflex results in blood pressure reduction and cardiac remodeling. For correct intraoperative electrode placement at the carotid bifurcation, the baroreceptor reflex needs to be activated several times. Many common anesthetic agents, such as inhalation anesthetics and propofol dampen or inhibit the baroreceptor reflex and complicate or even prevent successful placement. Therefore, a specific anesthesia and pharmacological management is necessary to ensure successful implantation of baroreceptor reflex stimulators.

The variability of baroreflex sensitivity in juvenile, spontaneously hypertensive rats

In this study the baroreflex sensitivity of conscious, juvenile, spontaneously hypertensive rats (SHRs) was compared. The study population consisted of 19 eight-week-old male SHRs. The baroreflex sensitivity was quantified as the derivative of the variation in heart rate (HR) and the variation of mean arterial pressure (baroreflex sensitivity = Delta HR/Delta MAP). MAP was manipulated with sodium nitroprusside (SNP) and phenylephrine (PHE), administered via an inserted cannula in the right femoral vein. The SHRs were divided into four groups: (1) low bradycardic baroreflex (LB) where the baroreflex gain (BG) was between 0 and 1 bpm/mmHg with PHE; (2) high bradycardic baroreflex (HB), where the BG was < -1 bpm/mmHg with PHE; (3) low tachycardic baroreflex (LT) where the BC was between 0 and 3 bpm/mmHg with SNP; (4) high tachycardic baroreflex (HT) where the BG was > 3 bpm/mmHg with SNP. We noted that 36.8% of the rats presented with an increased bradycardic reflex, while 27.8% demonstrated an attenuated tachycardic reflex. No significant alterations were noted regarding the basal MAP and HR. There were significant differences in the baroreflex sensitivity between SHRs in the same laboratory. One should be careful when interpreting studies employing the SHR as a research model.

Important GABAergic mechanism within the NTS and the control of sympathetic baroreflex in SHR

Inhibitory neurotransmission has an important role in the processing of sensory afferent signals in the nucleus of the solitary tract (NTS), particularly in spontaneously hypertensive rats (SHR). In the present study, we tested the hypothesis that gamma-aminobutyric acid (GABA) mediated neurotransmission within the NTS produces an inhibition of the baroreflex response of splanchnic sympathetic nerve discharge (sSND). In urethane-anesthetized, artificially ventilated and vagotomized male SHR and Wistar Kyoto (WKY) rats we compared baroreflex-response curves evoked after bilateral injections into the NTS of the GABA-A antagonist bicuculline (25 pmol/50 nl) or the GABA-B antagonist CGP 35348 (5 nmol/50 nl). Baseline MAP in SHR was higher than the WKY rats (SHR: 153+/-5, vs. WKY: 112+/-6 mm Hg, p<0.05). Bilateral injection of bicuculline or CGP 35348 into the NTS induced a transient (5 min) reduction in MAP (Delta = -26+/-4 and -41+/-6 mm Hg, respectively vs. saline Delta = +4+/-3 mm Hg, p<0.05) and sSND (Delta = -21+/-13 and -78+/-7%, respectively vs. saline: Delta = +6+/-4% p<0.05). Analysis of the baroreceptor curve revealed a decrease in the lower plateau (43+/-11 and 15+/-5%, respectively vs. saline: 78+/-6%, p<0.05) and an increase in the sympathetic gain of baroreflex (6.3+/-0.3, 7.2+/-0.8% respectively vs. saline: 4.2+/-0.4%, p<0.05). Bicuculline or CGP35348 into the NTS in WKY rats did not change MAP, sSND and sympathetic baroreflex gain. These data indicate that GABAergic mechanisms within the NTS act tonically reducing sympathetic baroreflex gain in SHR. Crown Copyright (C) 2010 Published by Elsevier By. All rights reserved.

Ablation of NK1 receptor bearing neurons in the nucleus of the solitary tract blunts cardiovascular reflexes in awake rats

The nucleus of the solitary tract (NTS) receives primary afferents involved in cardiovascular regulation. We investigated the role of NK1-receptor bearing neurons in the NTS on cardiovascular reflexes in awake rats fitted with chronic venous and arterial cannulae. These neurons were lesioned selectively with saporin conjugated with substance P (SP-SAP, 2 mu M, bilateral injections of 20 nL in the subpostremal NTS, or 200 nL in both the subpostremal and the commissural NTS). Before, and 7 and 14 days after injection of SP-SAP, we measured changes in blood pressure and heart rate induced by i.v. injection of phenylephrine and nitroprusside (baroreceptor reflex), cyanide (arterial chemoreceptor reflex), and phenylbiguanide (Bezold-Jarisch reflex). The smaller injections with SP-SAP completely abolished NK1 receptor staining in the subpostremal NTS. The larger injections abolished NK1 receptor immunoreactivity in an area that extended from the commissural NTS to the rostral end of the subpostremal NTS. The lesions seemed to affect only a limited number of neurons, since neutral red stained sections did not show any obvious reduction in cell number. The smaller lesions reduced the gain of baroreflex bradycardia and the hypotension induced by phenylbiguanide. The larger lesions completely abolished the response to phenylbiguanide, blocked the baroreflex bradycardia induced by phenylephrine, severely blunted the baroreflex tachycardia, and blocked the bradycardia and reduced the hypertension induced by cyanide. Thus, these responses depend critically on NK1-receptor bearing neurons in the NTS. (c) 2006 Elsevier B.V. All rights reserved.

EFFECT OF TESTOSTERONE ON THE PRESSOR-RESPONSE TO COMMON CAROTID OCCLUSION IN GONADECTOMIZED CONSCIOUS MALE-RATS WITH LESION OF THE MEDIAN-EMINENCE

The influence of testosterone on the development of the pressor response to common carotid occlusion was investigated in control and median eminence-lesioned male rats. In control rats (N = 9), gonadectomy performed 21 days before the experiments reduced by 22% (from 51 +/- 2 to 40 +/- 2 mmHg) and treatment with testosterone (300-mu-g for 4 days before the measurements) increased the initial peak pressor response (from 51 +/- 2 to 57 +/- 2 mmHg) which depends on carotid innervation. The maintained response which is of central origin (probably ischemic) was less affected. In nongonadectomized rats (N = 6), lesions of the median eminence (6 days) decreased the initial peak by 19% (from 52 +/- 2 to 42 +/- 3 mmHg) and the maintained response by 56% (from 32 +/- 2 to 14 +/- 1 mmHg). Sham-operated rats served as controls. In gonadectomized animals (N = 6) the lesion reduced only the maintained response (from 23 +/- 2 to 11 +/- 1 mmHg). Testosterone supplementation restored the maintained response but did not alter the initial peak. These results indicate that the pressor response to common carotid occlusion in male rats is modulated by testosterone and that the depression in the maintained response caused by median eminence lesion can be reversed by steroid supplementation.

Commissural NTS contributes to pressor responses to glutamate injected into the medial NTS of awake rats

In the present study we investigated whether interruption of the chemoreceptor reflex by an electrolytic lesion of the commissural subnucleus of the nucleus tractus solitarii (commNTS) influenced presser and bradycardic responses induced by microinjection of L-glutamate (L-Glu) into the medial NTS (mNTS) of conscious rats. Seven days after sham lesions, seven rats demonstrated significant presser [change in mean arterial pressure (MAP) = +33 +/- 3 mmHg] and bradycardic [change in heart rate (HR) = -74 +/- 8 beats/min (bpm)] responses to chemoreceptor reflex activation by intravenous injection of KCN. Likewise, L-Glu (1 nmol in 100 nl) injected into the mNTS in sham rats induced presser (+29 +/- 2 mmHg) and bradycardic responses (-90 +/- 8 bpm). However, in 11 rats with lesions in commNTS, presser and bradycardic chemoreceptor reflex responses were abolished, and injection of L-Glu into the mNTS decreased MAP (-14 +/- 6 mmHg) and HR (-59 +/- 16 bpm) as is reported in anesthetized control rats. We conclude that presser responses induced by L-Glu microinjected into the baroreceptor reflex region of mNTS in conscious rats depend on the integrity of the commNTS, which plays an important role in central chemoreceptor reflex pathways.

SEX-RELATED DIFFERENCES IN CARDIOVASCULAR-RESPONSES TO COMMON CAROTID OCCLUSION IN CONSCIOUS RATS

Mean arterial pressure and heart rate were determined in conscious, unrestrained groups of 10 male, female and androgenized female Wistar rats 20 s (early pressor response) and 1 min (late sustained response) after bilateral carotid artery occlusion. The early pressor response, which is of carotid reflex origin, was 40% greater in female than in male rats (45 +/- 2 vs 63 +/- 3 mmHg, respectively). The late sustained response, which is of central origin (probably ischemic), did not differ between male and female rats (32 +/- 2 vs 37 +/- 4 mmHg, respectively). The magnitude of the early pressor response of androgenized female tats (50 +/- 2 mmHg) was similar to that of male rats (45 +/- 2 mmHg) but the late sustained response was 19% smaller (26 +/- 2 mmHg). Common carotid occlusion caused increases in heart rate which were greater in female (51 +/- 9 and 34 +/- 9 beats/min in the early pressor response and late sustained response, respectively) than in male rats (31 +/- 5 and 8 +/- 4 beats/min, respectively). In androgenized female rats, heart rate decreased during common carotid occlusion (34 +/- 7 and 35 +/- 8 beats/min after 20 s and 1 min, respectively). These data provide evidence that there are substantial sex-related differences in the cardiovascular responses to common carotid occlusion in conscious rats and indicate that administration of androgens to newborn female rats affects the baroreceptor reflex control of their arterial pressure.

Effect of the gadolinium ion on body fluid regulation

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Lateral septal area alpha(1)-and alpha(2)-adrenoceptors differently modulate baroreflex activity in unanaesthetized rats

The lateral septal area (LSA) is a limbic structure involved in autonomic, neuroendocrine and behavioural responses. An inhibitory influence of the LSA on baroreflex activity has been reported; however, the local neurotransmitter involved in this modulation is still unclear. In the present study, we verified the involvement of local LSA adrenoceptors in modulating cardiac baroreflex activity in unanaesthetized rats. Bilateral microinjection of the selective a1-adrenoceptor antagonist WB4101 (10 nmol in a volume of 100 nl) into the LSA decreased baroreflex bradycardia evoked by blood pressure increases, but had no effect on reflex tachycardia evoked by blood pressure decreases. Nevertheless, bilateral administration of the selective a2-adrenoceptor antagonist RX821002 (10 nmol in 100 nl) increased baroreflex tachycardia without affecting reflex bradycardia. Treatment of the LSA with a cocktail containing WB4101 and RX821002 decreased baroreflex bradycardia and increased reflex tachycardia. The non-selective beta-adrenoceptor antagonist propranolol (10 nmol in 100 nl) did not affect either reflex bradycardia or tachycardia. Microinjection of noradrenaline into the LSA increased reflex bradycardia and decreased the baroreflex tachycardic response, an opposite effect compared with those observed after double blockade of a1- and a2-adrenoceptors, and this effect of noradrenaline was blocked by local LSA pretreatment with the cocktail containing WB4101 and RX821002. The present results provide advances in our understanding of the baroreflex neural circuitry. Taken together, data suggest that local LSA a1- and a2-adrenoceptors modulate baroreflex control of heart rate differently. Data indicate that LSA a1-adrenoceptors exert a facilitatory modulation on baroreflex bradycardia, whereas local a2-adrenoceptors exert an inhibitory modulation on reflex tachycardia.

Exercise training normalizes an increased neuronal excitability of NTS-projecting neurons of the hypothalamic paraventricular nucleus in hypertensive rats

Stern JE, Sonner PM, Son SJ, Silva FC, Jackson K, Michelini LC. Exercise training normalizes an increased neuronal excitability of NTS-projecting neurons of the hypothalamic paraventricular nucleus in hypertensive rats. J Neurophysiol 107: 2912-2921, 2012. First published February 22, 2012; doi:10.1152/jn.00884.2011.-Elevated sympathetic outflow and altered autonomic reflexes, including impaired baroreflex function, are common findings observed in hypertensive disorders. Although a growing body of evidence supports a contribution of preautonomic neurons in the hypothalamic paraventricular nucleus (PVN) to altered autonomic control during hypertension, the precise underlying mechanisms remain unknown. Here, we aimed to determine whether the intrinsic excitability and repetitive firing properties of preautonomic PVN neurons that innervate the nucleus tractus solitarii (PVN-NTS neurons) were altered in spontaneously hypertensive rats (SHR). Moreover, given that exercise training is known to improve and/or correct autonomic deficits in hypertensive conditions, we evaluated whether exercise is an efficient behavioral approach to correct altered neuronal excitability in hypertensive rats. Patch-clamp recordings were obtained from retrogradely labeled PVN-NTS neurons in hypothalamic slices obtained from sedentary (S) and trained (T) Wistar-Kyoto (WKY) and SHR rats. Our results indicate an increased excitability of PVN-NTS neurons in SHR-S rats, reflected by an enhanced input-output function in response to depolarizing stimuli, a hyperpolarizing shift in Na+ spike threshold, and smaller hyperpolarizing afterpotentials. Importantly, we found exercise training in SHR rats to restore all these parameters back to those levels observed in WKY-S rats. In several cases, exercise evoked opposing effects in WKY-S rats compared with SHR-S rats, suggesting that exercise effects on PVN-NTS neurons are state dependent. Taken together, our results suggest that elevated preautonomic PVN-NTS neuronal excitability may contribute to altered autonomic control in SHR rats and that exercise training efficiently corrects these abnormalities.

Beeinflusst die Stärke der Stressreaktion in der Post-Akquisitionsphase das Identitätsgedächtnis von Gesichtern?

Stress in der Post-Akquisitionsphase begünstigt die Gedächtniskonsolidierung emotional erregender Informationen. Das Zusammenspiel von noradrenerger Aktivierung und Cortisol auf Ebene der Amygdala ist hierbei von entscheidender Bedeutung. rnIn dieser Studie wird untersucht, ob dieser Effekt durch das Ausmaß der kardiovaskulären bzw. der subjektiv erlebten Stressreaktivität beeinflusst wird. 49 Probanden (Alter: 23.8 Jahre; 32 Frauen) wurden je 52 Gesichter, davon 50% mit ärgerlichem sowie 50 % mit glücklichem Ausdruck präsentiert. Sofort nach Akquisition wurde bei 30 Probanden akuter Stress durch den sozial evaluierten Kaltwassertest (SECPT; Eintauchen der dominanten Hand in eiskaltes Wasser für 3 Minuten unter Beobachtung) induziert, bei 19 Probanden wurde eine Kontrollprozedur ohne Stress durchgeführt. Die 30 Probanden der SECPT-Gruppe wurden post-hoc zum einen anhand der individuellen Blutdruckreaktivität und zum zweiten anhand der Stärke der subjektiv bewerteten Stressreaktivität per Mediansplit in zwei Subgrupen unterteilt (High Responder, Low Responder). rnDer erste Wiedererkennungstest fand 30 Minuten nach der Akquisitionsphase, ein weiterer 20 Stunden später statt. Zu den Testzeitpunkten wurden jeweils 26 der initial präsentierten Gesichter mit neutralem Gesichtsausdruck gezeigt sowie 26 neue neutrale Gesichter. rnDie Kontrollgruppe und die Gruppe der High Responder (basierend auf der kardiovaskulären Reaktivität) zeigten ein besseres Erinnerungsvermögen für die initial positiv präsentierten gesichter, wohingegen die Gruppe der Low Responder ein besseres Gedächtnis für die initial negativ präsentierten Gesichter aufwies. rnStress scheint abhängig von der Stärke der kardiovaskulären Reaktion zu valenzspezifischen Konsolidierungseffekten zu führen. Hierbei könnten viszerale Afferenzen z.B. der arteriellen Baroreflexe eine Rolle spielen. rn

Intrinsically photosensitive melanopsin retinal ganglion cell contributions to the pupillary light reflex and circadian rhythm

Recently discovered intrinsically photosensitive melanopsin retinal ganglion cells contribute to the maintenance of pupil diameter, recovery and post-illumination components of the pupillary light reflex and provide the primary environmental light input to the suprachiasmatic nucleus for photoentrainment of the circadian rhythm. This review summarises recent progress in understanding intrinsically photosensitive ganglion cell histology and physiological properties in the context of their contribution to the pupillary and circadian functions and introduces a clinical framework for using the pupillary light reflex to evaluate inner retinal (intrinsically photosensitive melanopsin ganglion cell) and outer retinal (rod and cone photoreceptor) function in the detection of retinal eye disease.