The hypothalamic paraventricular nucleus (PVN) is a central site for integration of the endocrine system and the autonomic nervous system. Despite a number of studies have pointed out the importance of the PVN in the central regulation of cardiovascular functions, the chemical mediators in the PVN responsible for mediating baroreflex are not well understood. In the present study, we used the conscious rats to investigate the possible involvement of glycine (Gly) in PVN in the central regulation of baroreflex induced by intravenous injection of phenylephrine (0.8 mug/0.04 mL, in 3 min). Then, the microdialysis sampling was performed in the PVN and the concentration of Gly in the microdialysate was measured by high performance liquid chromatography (HPLC) combined with electrochemical techniques, and mean arterial pressure (MAP) and heart rate (HR) were recorded simultaneously. Injection of phenylephrine elicited a significant increase (P<0.01) in MAP from the baseline of (99.5+/-14.2) mmHg to the maximum of (149.8+/-19.5) mmHg and a decrease (P<0.01) in HR from the baseline of (400.8+/-33.1) beats/min to the minimum of (273.4+/-40.8) beats/min, respectively. Synchronously, the injection of phenylephrine increased the level of Gly in the microdialysate from the PVN to (162.9+/-27.3)% of the basal level (P<0.05). Perfusion of strychnine (100 mumol/L), an antagonist of Gly receptor, into the PVN enhanced the pressor response and attenuated the bradycardic response during the baroreflex, resulting in a decrease in baroreflex sensitivity (P<0.001). Whereas, the perfusion of Gly (1 mmol/L) into the PVN did not affect the pressor response but enhanced the bradycardic response during the baroreflex, resulting in an increase in baroreflex sensitivity (P<0.001). These results suggest that endogenous Gly in the PVN may act via strychnine-sensitive Gly receptor to produce a facilitative effect on baroreflex.
Animals ; Baroreflex ; drug effects ; Glycine ; pharmacology ; Heart Rate ; Microinjections ; Paraventricular Hypothalamic Nucleus ; physiology ; Phenylephrine ; pharmacology ; Rats

AIMTo explore the role of histaminergic receptors in the nucleus tractus solitarius (NTS) in the responses of carotid baroreflex (CBR) performance to the intracerebroventricular (ICV) injection of histamine (HA).

METHODSThe left and right carotid sinus regions were isolated from the systemic circulation in 18 Wistar rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure (ISP) was altered in a stepwise manner. ISP-mean arterial pressure (MAP) relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. We observed the changes in CBR performance induced by ICV HA and the effects of pretreatment with HA receptors antagonists into the NTS on the responses of CBR to HA.

RESULTSICV injection of HA (100 ng) significantly shifted the ISP-MAP relationship curve upwards and moved the middle part of ISP Gain relationship curve downwards, and reduced the MAP range and maximum gain (Gmax), but increased the threshold pressure (TP), saturation pressure(SP) and ISP at Gmax (ISP(Gmax)). The pretreatment with H1 or H2 receptors antagonist, chlorpheniramine (CHL, 0.5 microg) or cimetidine (CIM, 1.5 microg) into the NTS, could obviously diminish the above-mentioned changes in CBR performance induced by HA, but the effect of CIM was less remarkable than that of CHL.

CONCLUSIONThe intracerebroventricular administration of HA results in a rapid resetting of CBR and a decrease in reflex sensitivity, and the histaminergic receptors in the NTS (H1 and H2 receptors), especially H1 receptors might play an important role in the responses of CBR to HA, and furthermore, the effects of the central HA on CBR might be related to a histaminergic descending pathway from the hypothalamus to NTS.

Animals ; Baroreflex ; drug effects ; Carotid Sinus ; drug effects ; Cerebral Ventricles ; Histamine ; pharmacology ; Male ; Rats ; Rats, Wistar ; Receptors, Histamine ; metabolism ; Solitary Nucleus ; drug effects

AIMTo investigate the roles of alpha1 and alpha2 receptors in the nucleus tractus solitarius (NTS) in the carotid baroreflex (CBR) resetting induced by the intracerebroventricular injection (ICV) of histamine (HA).

METHODSThe left and right carotid sinus regions were isolated from the systemic circulation in 25 Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure (ISP) was altered in a stepwise manner. ISP-mean arterial pressure (MAP) relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CBR performance induced by ICV HA and the effects of pretreatment with alpha1 or alpha2 receptor antagonist into the NTS on the responses of CBR to HA were examined.

RESULTSICV HA (60 micromol x L(-1) in 5 microl) significantly shifted the ISP-MAP relationship curve upwards (P < 0.05) and moved the middle part of ISP-Gain relationship curve downwards (P < 0.05), and reduced the MAP range and maximum gain (P < 0.05). The pretreatment with phenoxybenzamine (PBZ, a selective antagonist of alpha1 receptor, 3 micromol x L(-1) in 500 nl) or yohimbine (YOH, a selective antagonist of alpha2 receptor, 2.5 micromol x L(-1) in 500 nl) into the NTS could obviously intensify the above-mentioned changes in CBR performance induced by HA, but the intensive effect of PBZ was less remarkable than that of YOH (P < 0.05).

CONCLUSIONThe intracerebroventricular administration of HA results in a rapid resetting of CBR and a decrease in reflex sensitivity, and the functions of alpha1 and alpha2 receptors in the NTS might weaken CBR resetting induced by ICV HA. Furthermore, alpha2 receptor in the NTS might play an more important role in modulating the responses of CHR to HA.

Animals ; Baroreflex ; drug effects ; Blood Pressure ; Carotid Sinus ; drug effects ; Histamine ; administration & dosage ; pharmacology ; Injections, Intraventricular ; Male ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus ; drug effects ; physiology

The changes in carotid sinus baroreceptor reflex (CSR) performance induced by intracerebroventricular injection (i.c.v.) of histamine (HA) were investigated. The effects of pretreatment with HA receptors antagonists into the cerebroventricle or nucleus of solitary tract (NTS) on the responses of CSR to HA were also examined. Intracarotid sinus pressure (ISP)-mean arterial pressure (MAP) relationship curve was constructed by fitting to the logistic function with five parameters in 50 Wistar rats anesthetized with pentobarbital sodium. The left and right carotid sinus regions were isolated from the systemic circulation and the ISP was altered in a stepwise manner. The main results obtained are as follows. (1) i.c.v. injection of HA (100 ng) significantly shifted the ISP-MAP relationship curve upwards and moved the middle part of ISP-Gain relationship curve downwards, and reduced the MAP range and maximum gain (G(max)), but increased the threshold pressure (TP), saturation pressure (SP) and ISP at G(max) (ISP (Gmax)). (2) The pretreatment with H(1) or H(2) receptors antagonist, chlorpheniramine (CHL, 5 microg) or cimetidine (CIM, 15 microg), could obviously diminish the above-mentioned changes in CSR performance induced by HA, but the effect of CIM was less remarkable than that of CHL. (3) The pretreatment with both CHL and CIM (5 microg and 15 microg) at the same time abolished the responses of CSR performance to HA completely. (4) After microinjection of CHL (0.5 microg) or CIM (1.5 microg) into the NTS, the responses of CSR to HA were similar to those after i.c.v. CHL or CIM, but the change in TP was significantly decreased. These findings suggest that the intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity. The response of CSR to HA might be mediated by both central H(1) and H(2) receptors, especially by H(1) receptors. The effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to NTS. It is suggested that the HA receptors in the NTS play an important role in the responses of CSR to HA.
Animals ; Baroreflex ; drug effects ; physiology ; Carotid Sinus ; physiology ; Histamine ; administration & dosage ; pharmacology ; Lateral Ventricles ; Male ; Pressoreceptors ; physiology ; Rats ; Rats, Wistar

AIMTo investigate the effects of alpha1 and alpha2 receptors in the locus ceruleus (LC) on carotid baroreflex (CBR) resetting induced by intracerebroventricular injection (ICV) of histamine (HA).

METHODSThe left and right carotid sinus regions were isolated from the systemic circulation in 23 Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure (ISP) was altered in a stepwise manner. ISP-mean arterial pressure (MAP) relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CBR performance induced by ICV HA and the effects of pretreatment with alpha1 or alpha2 receptor antagonist into the LC on the responses of CBR to HA were examined.

RESULTSICV HA (60 micromol x L(-1) in 5 microl) significantly shifted the ISP-MAP relationship curve upwards (P < 0.05) and reduced the MAP range and maximum gain (P < 0.05). The pretreatment with phenoxybenzamine (PBZ, a selective antagonist of alpha1 receptor, 3 micromol x L(-1) in 500 nl) or yohimbine (YOH, a selective antagonist of alpha2 receptor, 2.5 micromol x L(-1) in 500 nl) into the LC could obviously intensify the above-mentioned changes in CBR performance induced by HA, but the intensive effect of PBZ was less remarkable than that of YOH (P < 0.05).

CONCLUSIONThe intracerebroventricular administration of HA results in a rapid resetting of CBR and a decrease in reflex sensitivity, and the functions of alpha1 and alpha2 receptors in the LC may attenuate CBR resetting induced by ICV HA. Furthermore, alpha2 receptor in the LC might play a more important role in regulating the responses of CBR to HA.

Animals ; Baroreflex ; drug effects ; physiology ; Carotid Sinus ; Histamine ; pharmacology ; Locus Coeruleus ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Neurotransmitter

OBJECTIVETo investigate whether transdermal scopolamine increased cardiac vagal activity in patients during the acute phase of myocardial infarction.

METHODS30 patients with a first acute myocardial infarction and preserved sinus rhythm who were on no drug that could influence the sinus node were randomly assigned to either treatment group or placebo group. Measures of heart rate variability (HRV) in patients given drug or placebo were obtained by digital 24 hour Holter recording before and after treatment. Baroreflex sensitivity was performed using the phenylephrine method.

RESULTSNo significant differences was found in the indices of the time domain and the frequency domain in both groups before treatment. Patients with transdermal scopolamine showed a significant increase in the standard deviation of normal RR intervals (SDNN), standard deviation of all five min mean normal RR intervals (SDANN), root mean square of differences of successive normal RR intervals (rMSSD), total power (TP, 0.000. - 0.40 Hz), low frequency peak (LF, 0.040 - 0.15 Hz), high frequency peak (HF, 0.15 - 0.40 Hz), and Baroreflex sensitivity after treatment (P < 0.05 - 0.01). These indices did not change in patients given placebo.

CONCLUSIONLow doses of transdermal scopolamine safely increase cardiac parasympathetic activity and improve autonomic indices in patients with acute myocardial infarction.

Administration, Cutaneous ; Adult ; Aged ; Baroreflex ; drug effects ; Dose-Response Relationship, Drug ; Female ; Heart ; innervation ; Heart Rate ; drug effects ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; physiopathology ; Scopolamine Hydrobromide ; pharmacology ; Vagus Nerve ; drug effects ; physiopathology

The effects of capsaicin (CAP) on the carotid sinus baroreflex were studied in 30 anaesthetized rats with perfused isolated carotid sinus. The results are as follows. (1) By perfusing the isolated carotid sinus with CAP (1 micromol/L), the functional curve of the baroreflex was shifted to the left and downward, with a peak slope (PS) increasing from 0.34+/-0.01 to 0.42+/-0.01 (P<0.01), whereas the reflex decrease (RD) in mean arterial pressure was enhanced from 36.51+/-1.26 to 45.01+/-0.71 mmHg (P<0.01). Meanwhile, the threshold pressure, equilibrium pressure and saturation pressure were all significantly decreased from 70.43 +/-2.09 to 52.86 +/-2.80 mmHg (P<0.01), 95.5+/-1.71 to 87.00+/-1.58 mmHg (P<0.01) and 177.60+/-1.37 to 163.55+/-2.12 mmHg (P<0.01), respectively. Among the functional parameters of carotid baroreflex, the changes in PS and RD induced by capsaicin were dose-dependent. (2) By pretreatment with ruthenium red (RR, 100 micromol/L), an antagonist of vanilloid receptor subtype 1 (VR(1)), the above effects of CAP on carotid baroreflex were abolished. (3) The CAP-induced change in the baroreflex was also eliminated by pretreatment with glibenclamide (20 microm ol/L), a K(ATP) channel blocker. On the basis of the results, it is concluded that CAP facilitates the carotid baroreflex, an effect of which may be resulted from the opening of K(ATP) channels mediated by VR(1).
Animals ; Baroreflex ; drug effects ; Blood Pressure ; drug effects ; Capsaicin ; pharmacology ; Carotid Sinus ; drug effects ; physiology ; Glyburide ; pharmacology ; In Vitro Techniques ; Male ; Potassium Channel Blockers ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Drug ; antagonists & inhibitors ; Ruthenium Red ; pharmacology ; TRPV Cation Channels

AIMTo investigate the possible involvement of glutamate(Glu) in the paraventricular nucleus (PVN) in the central regulation of baroreflex.

METHODSThe baroreflex was induced by intravenous injection of phenylephrine in conscious rats, and the extracellular concentration of Glu in the PVN region was measured by microdialysis and high performance liquid chromatography (HPLC) techniques. To determine whether the observed Glu release was involved in the baroreflex, NMDA and non-NMDA receptor antagonists, MK-801 and CNQX, were perfused in the PVN region during baroreflex.

RESULTSDuring baroreflex, the Glu concentration in the PVN region immediately increased to 384.82% +/- 91.77% of basal level (P < 0.01). (2) During baroreflex, direct perfusion of MK-801 and CNQX in the PVN were attenuated the increase of blood pressure and enhanced the decrease of HR (P < 0.01),resulting a significant increase in baroreflex sensitivity (P < 0.01).

CONCLUSIONGlutamate in PVN is involved in central regulation of baroreflex, which may inhibit baroreflex via ionothopic glutamate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione ; pharmacology ; Animals ; Baroreflex ; drug effects ; physiology ; Dizocilpine Maleate ; pharmacology ; Excitatory Amino Acid Antagonists ; pharmacology ; Male ; Paraventricular Hypothalamic Nucleus ; physiology ; Rats ; Rats, Wistar

The role of atrial natriuretic peptide (ANP) in the central regulation of the circulation is known to be a neurotransmitter or a neuromodulator, but its actions on baroreceptor reflex function are not fully resolved. The present study examined the role of ANP (6, 60 ng/0.2 microl) by direct microinjection into the hypothalamic paraventricular nucleus (PVN) in conscious rats. OPC-21268 (0.45 microg/3 microl), an antagonist of the V(1) receptor, was microinjected into the lateral ventricle to examine whether the effect of ANP on baroreflex sensitivity is mediated by vasopressin (VP). ANP significantly increased the baroreflex sensitivity, and OPC-21268 attenuated the increase of baroreflex sensitivity induced by ANP. Intravenous injections of ANP (60 ng/0.04 ml) did not affect baroreflex sensitivity. These results suggest that ANP in the PVN may produce a facilitative effect on baroreflex, and the effect may be via, at least in part, the central vasopressin.
Animals ; Atrial Natriuretic Factor ; pharmacology ; physiology ; Baroreflex ; drug effects ; physiology ; Male ; Microinjections ; Paraventricular Hypothalamic Nucleus ; physiology ; Random Allocation ; Rats ; Rats, Wistar

Volatile anesthetics alter the arterial baroreflex (BRX) but its mechanisms are poorly understood. This study was designed to determine the effect of 1 and 2 minimal alveolar concentrations (MAC) of enflurane on the BRX parameters in unanesthetized brain stem-intact and decerebrate rats. Under enflurane anesthesia, the femoral artery and both femoral vein were catheterized for pressor (phenylephrine) and depressor (nitroprusside) drug delivery and continuous blood pressure measurements. Decerebration was performed at midcollicular level. BRX tests were performed in 3 time periods; before enflurane (conscious brain-intact), during 1 or 2 MAC enflurane exposure 1 hour after a sham operation or a decerebration operation, and 2 hours after the termination of enflurane (zero enflurane). Mean arterial pressure (MAP) and heart rate (HR) were fitted to a sigmoid logistic equation, the Boltzman equation. The curve of best fit was obtained with a computer program. 1 MAC and 2 MAC of enflurane shifted MAP-HR baroreflex curves to the left in the all groups and significantly attenuated the baroreflex range. The slope of conscious intact period and zero enflurane period of each group did not change significantly, but during the enflurane period the slope was significantly lowered. Enflurane depressed the baroreflex sensitivity (slope) and the HR range in a similar dose-dependant manner in both brain stem-intact and decerebrate rats. Such results draw into question whether the suprapontine sites contribute to enflurane's actions on cardiovascular autonomic regulation.
Anesthetics, Inhalation/*pharmacology ; Animals ; Baroreflex/*drug effects ; Blood Pressure/drug effects ; Carbon Dioxide/blood ; Decerebrate State ; Enflurane/*pharmacology ; Heart Rate/*drug effects ; Hydrogen-Ion Concentration ; Male ; Oxygen/blood ; Rats ; Rats, Sprague-Dawley ; Support, Non-U.S. Gov't