Activation of the central histaminergic system mediates arachidonic-acid-induced cardiovascular effects

2014 ◽  
Vol 92 (8) ◽  
pp. 645-654 ◽  
Author(s):  
Burcin Altinbas ◽  
Bora Burak Topuz ◽  
Tuncay İlhan ◽  
Mustafa Sertac Yilmaz ◽  
Hatice Erdost ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Receptor Antagonist ◽  
Cardiovascular Effects ◽  
Posterior Hypothalamus ◽  
Sprague Dawley ◽  
H2 Receptor Antagonist ◽  
Histaminergic System ◽  
Histaminergic Neurons ◽  
H4 Receptor ◽  
Cox 1

The aim of this study was to explain the involvement of the central histaminergic system in arachidonic acid (AA)-induced cardiovascular effects in normotensive rats using hemodynamic, immunohistochemistry, and microdialysis studies. Intracerebroventricularly (i.c.v.) administered AA (0.25, 0.5, and 1.0 μmol) induced dose- and time-dependent increases in mean arterial pressure and decreased heart rate in conscious normotensive Sprague–Dawley rats. Central injection of AA (0.5 μmol) also increased posterior hypothalamic extracellular histamine levels and produced strong COX-1 but not COX-2 immunoreactivity in the posterior hypothalamus of rats. Moreover, the cardiovascular effects and COX-1 immunoreactivity in the posterior hypothalamus induced by AA (0.5 μmol; i.c.v.) were almost completely blocked by the H2 receptor antagonist ranitidine (50 and 100 nmol; i.c.v.) and partially blocked by the H1 receptor blocker chlorpheniramine (100 nmol; i.c.v.) and the H3–H4 receptor antagonist thioperamide (50 and 100 nmol; i.c.v.). In conclusion, these results indicate that centrally administered AA induces pressor and bradycardic responses in conscious rats. Moreover, we suggest that AA may activate histaminergic neurons and increase extracellular histamine levels, particularly in the posterior hypothalamus. Acting as a neurotransmitter, histamine is potentially involved in AA-induced cardiovascular effects under normotensive conditions.

Endorphinergic mechanism in the central cardiovascular and analgesic effects of clonidine

1987 ◽  
Vol 65 (8) ◽  
pp. 1624-1632 ◽  
Author(s):  
G. Kunos ◽  
R. Mosqueda-Garcia ◽  
J. A. Mastrianni ◽  
F. V. Abbott
Keyword(s):  
Receptor Antagonist ◽  
Arcuate Nucleus ◽  
Monosodium Glutamate ◽  
Opiate Receptors ◽  
Cardiovascular Effects ◽  
Male Rats ◽  
Sprague Dawley ◽  
Wky Rats ◽  
Sd Rats ◽  
Wistar Kyoto

In urethane-anesthetized male rats, injection of 5 nmol clonidine into the nucleus of the solitary tract (NTS) causes hypotension and bradycardia. These effects are greater in spontaneously hypertensive rats (SHR) and normotensive Sprague–Dawley (SD) rats than in normotensive Wistar–Kyoto (WKY) rats. The effects of clonidine are stereoselectively inhibited by 100 ng intra-NTS naloxone in SHR and SD but not in WKY rats. In SHR, the effects of clonidine are also inhibited by intra-NTS administration of ICI 174864 (a δ-receptor antagonist) but not by β-funaltrexamine (a μ-receptor antagonist), while in SD rats only the μ- and not the δ-antagonist was effective. Neonatal treatment of SHR with monosodium glutamate (MSG) reduced the β-endorphin content of the arcuate nucleus and the NTS, reduced the cardiovascular effects of clonidine, and abolished their naloxone sensitivity. MSG treatment of newborn WKY reduced the β-endorphin content of the arcuate nucleus but not the NTS and did not affect the responses to clonidine. Measurement of pain sensitivity by the formalin test indicated that clonidine was more potent as an analgesic in SHR and SD than in WKY rats, and its effect was inhibited by naloxone (2 mg/kg i.p.) in the former two strains but not in WKY. It is proposed that a naloxone-sensitive component of the cardiovascular effects of clonidine is due to release of a β-endorphin-like opioid from the NTS, and that this mechanism is present in SHR and SD but not in WKY rats. The opiate receptors mediating the effects of the opioid appear to be of the μ-subtype in SD rats and of the δ-subtype in SHR. The results also support a close relationship between central cardiovascular and pain regulatory mechanisms.

scholarly journals Effect of blockade of postsynaptic H1 or H2 receptors or activation of presynaptic H3 receptors on catecholamine-induced stimulation of ACTH and prolactin secretion

2000 ◽  
pp. 637-641 ◽  
Author(s):  
E Willems ◽  
U Knigge ◽  
H Jorgensen ◽  
A Kjaer ◽  
J Warberg
Keyword(s):  
Receptor Antagonist ◽  
Prolactin Secretion ◽  
Male Rats ◽  
H2 Receptor Antagonist ◽  
Histaminergic System ◽  
Intracerebroventricular Infusion ◽  
H2 Receptors ◽  
H3 Receptors ◽  
Prolactin Response ◽  
Stimulation Of

The effect of inhibition of the neuronal histaminergic system by blockade of postsynaptic H1 or H2 receptors or activation of presynaptic H3 autoreceptors on the ACTH and prolactin responses to the catecholamines epinephrine and norepinephrine was investigated in conscious male rats. Intracerebroventricular infusion of epinephrine and norepinephrine stimulated ACTH and prolactin secretion. Prior intracerebroventricular infusion of the H1 receptor antagonist, mepyramine, or the H2 receptor antagonist, cimetidine, had no effect on the ACTH response to epinephrine or norepinephrine, while these responses were inhibited by pretreatment with the H3 receptor agonist, imetit. The prolactin response to norepinephrine was significantly inhibited by pretreatment with mepyramine, cimetidine or imetit whereas the three histaminergic compounds had no effect on the prolactin response to epinephrine. The findings suggest that the histaminergic system exerts a mediating or permissive action on the norepinephrine-induced stimulation of prolactin secretion, whereas an intact histaminergic system may not be required for catecholamines to stimulate ACTH secretion. The inhibitory effect of imetit on catecholamine-induced release of ACTH may be due to an activation of H3 receptors located presynaptically on non-histaminergic neurons, e.g. aminergic neurons. The study further indicates an important role of histamine in the neuroendocrine regulation of prolactin secretion.

scholarly journals Antagonism of orexin receptors in the posterior hypothalamus reduces hypoglossal and cardiorespiratory excitation from the perifornical hypothalamus

2013 ◽  
Vol 114 (1) ◽  
pp. 119-130 ◽  
Author(s):  
Georg M. Stettner ◽  
Leszek Kubin
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Respiratory Rate ◽  
Receptor Antagonist ◽  
Hypoglossal Nerve ◽  
Posterior Hypothalamus ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Orexin Receptors ◽  
Sprague Dawley Rats

The perifornical (PF) region of the posterior hypothalamus promotes wakefulness and facilitates motor activity. In anesthetized rats, local disinhibition of PF neurons by GABAA receptor antagonists activates orexin (OX) neurons and elicits a systemic response, including increases of hypoglossal nerve activity (XIIa), respiratory rate, heart rate, and blood pressure. The increase of XIIa is mediated to hypoglossal (XII) motoneurons by pathways that do not require noradrenergic or serotonergic projections. We hypothesized that the pathway might include OX-dependent activation locally within the PF region or direct projections of OX neurons to the XII nucleus. Adult, male Sprague-Dawley rats were urethane anesthetized, vagotomized, paralyzed, and ventilated. Gabazine (GABAA receptor antagonist, 0.18 mM, 20 nl) was injected into the PF region, and ∼2 h later, a second gabazine injection was performed preceded by injection of a dual OX1/2 receptor antagonist (almorexant; 90 mM) either into the XII nucleus (40–60 nl at 2–3 rostrocaudal levels; n = 6 rats), or into the PF region (40–60 nl; n = 6 rats). XIIa, respiratory rate, heart rate, and arterial blood pressure were analyzed for 70 min after each gabazine injection. The excitatory effects of PF gabazine on XIIa, respiratory, and heart rates were significantly reduced by up to 44–82% when gabazine injections were preceded by PF almorexant injections, but not when almorexant was injected into the XII nucleus. These data suggest that a significant portion of XII motoneuronal and cardiorespiratory activation evoked by disinhibition of PF neurons is mediated by local OX-dependent mechanisms within the posterior hypothalamus.

scholarly journals The Intermediation Role of Central Cyclooxygenase Products TXA2, PGF2α, PGE, and PGD in Orexin-evoked Cardiovascular Effects

2021 ◽  
Author(s):  
Burçin Altınbaş ◽  
Gökcen Guvenc Bayram ◽  
Murat Yalcin
Keyword(s):  
Receptor Antagonist ◽  
Cardiovascular Effects ◽  
Cardiovascular Responses ◽  
Mediating Effects ◽  
Sprague Dawley ◽  
Synthesis Inhibitor ◽  
Sprague Dawley Rats ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites

Abstract Centrally injected some prostaglandins (PG) and orexin (OX) produce similar cardiovascular responses. We have recently reported that both central cyclooxygenase (COX) and central lipoxygenase (LOX) enzymes mediate the cardiovascular effects of OX. In the current study, we aimed to investigate the mediating effects of thromboxane (TX) A2, PGD, PGE, and PGF2a, as COX pathway subproducts known to be active in cardiovascular control, on cardiovascular responses elicited by OX. Intracerebroventricular (i.c.v.) injection of OX increased cardiovascular levels in normotensive male Sprague Dawley rats. Moreover, central pretreatment with the TXA2 synthesis inhibitor furegrelate, PGF2α receptor antagonist, PGF2α-dimethylamine, PGE, and PGD receptor antagonist AH6809 partially attenuated the centrally administered OX -induced pressor and tachycardic cardiovascular responses in rats. In conclusion, our results show that i.c.v. injection of OX increases blood pressure and heart rate. Moreover, TXA2, PGF2α, PGE, and PGD mediate, at least in part, the centrally applied OX -evoked pressor and tachycardic responses. The results suggest that centrally injected OX -evoked pressor and tachycardia responses may also be mediated by arachidonic acid metabolites other than TXA2, PGF2α, PGE, and PGD.

Central mechanism underlying pressor and bradycardic effect of intracerebroventricularly injected arachidonic acid

2011 ◽  
Vol 89 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Murat Yalcin
Keyword(s):  
Heart Rate ◽  
Arachidonic Acid ◽  
Cardiovascular Effect ◽  
Cardiovascular Effects ◽  
Central Mechanism ◽  
Sprague Dawley ◽  
Synthesis Inhibitor ◽  
Sprague Dawley Rats ◽  
Cox Inhibitor ◽  
Different Doses

The aim of the current study was to determine the central cyclooxygenase (COX) pathway and central thromboxane signaling in the cardiovascular effects evoked by arachidonic acid (AA). As a main control for the study, different doses of AA (75, 150, or 300 µg) were administered intracerebroventricularly (i.c.v.). Centrally injected AA dose- and time-dependently increased mean arterial pressure and decreased heart rate in conscious normotensive Sprague–Dawley rats. The maximal cardiovascular effects of AA were observed at min 10 of the injection and lasted almost 30 min. To investigate the central mechanism of the AA-induced cardiovascular effect in conscious normotensive animals, pretreatment with nonselective COX inhibitor indomethacin (200 µg; i.c.v.), thromboxane A2 (TXA2) synthesis inhibitor furegrelate (250 or 500 µg; i.c.v.), or TXA2 receptor antagonist SQ-29548 (8 or 16 µg; i.c.v.) was carried out 15 min before AA (150 µg; i.c.v.) injection. While indomethacin completely prevented the pressor and bradycardic responses to AA, furegrelate and SQ-29548 attenuated these effects in part in awake normotensive rats. In conclusion, these findings suggest that the pressor and bradycardic cardiovascular effects of centrally injected AA are dependent on COX activity being totally central and the TXA2 signaling pathway being subsequently central, at least in part.

scholarly journals Arachidonic Acid Metabolites of CYP450 Enzymes and HIF-1α Modulate Endothelium-Dependent Vasorelaxation in Sprague-Dawley Rats under Acute and Intermittent Hyperbaric Oxygenation

2020 ◽  
Vol 21 (17) ◽  
pp. 6353
Author(s):  
Zrinka Mihaljević ◽  
Anita Matić ◽  
Ana Stupin ◽  
Ruža Frkanec ◽  
Branka Tavčar ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Hyperbaric Oxygenation ◽  
Epoxyeicosatrienoic Acid ◽  
Sprague Dawley ◽  
Single Exposure ◽  
Ctrl Group ◽  
Sprague Dawley Rats ◽  
Acid Metabolites ◽  
Cox 1

Acetylcholine-induced vasorelaxation (AChIR) and responses to reduced pO2 (hypoxia-induced relaxation (HIR), 0% O2) were assessed in vitro in aortic rings of healthy male Sprague-Dawley rats (N = 252) under hyperbaric (HBO2) protocols. The studied groups consisted of the CTRL group (untreated); the A-HBO2 group (single HBO2; 120 min of 100% O2 at 2.0 bars); the 24H-HBO2 group (examined 24 h after single exposure) and the 4D-HBO2 group (four consecutive days of single HBO2). AChIR, sensitivity to ACh and iNOS expression were decreased in the A-HBO2 group. HIR was prostanoid- and epoxyeicosatrienoic acid (EET)-mediated. HIF-1α expression was increased in the 24H-HBO2 and 4D-HBO2 groups. LW6 (HIF-1α inhibitor) decreased HIR in the 24H-HBO2 group. HBO2 affected the expression of COX-1 and COX-2. CYP2c11 expression was elevated in the 24H-HBO2 and 4D-HBO2 groups. Concentrations of arachidonic acid (AA) metabolites 14(15)-DiHET, 11(12)-DiHET and 8(9)-DiHET were increased in A-HBO2 and 24H-HBO2. An increased concentration of 8(9)-EET was observed in the A-HBO2 and 24h-HBO2 groups vs. the CTRL and 4D-HBO2 groups, and an increased concentration of 5(6)-DiHET was observed in the 24H-HBO2 group vs. the 4D-HBO2 group. The 20-HETE concentration was increased in the A-HBO2 group. All were determined by LC-MS/MS of the aorta. The results show that AChIR in all groups is mostly NO-dependent. HIR is undoubtedly mediated by the CYP450 enzymes’ metabolites of AA, whereas HIF-1α contributes to restored HIR. Vasoconstrictor metabolites of CYP450 enzymes contribute to attenuated AChIR and HIR in A-HBO2.

scholarly journals Involvement of central histaminergic system in cardiovascular effects of Y1 receptor antagonist BIBP 3226 in haemorrhagic shock in rats

2017 ◽  
Vol 71 ◽  
pp. 357-362
Author(s):  
Adam Krawiec ◽  
Karolina Jasikowska ◽  
Katarzyna Chojnacka ◽  
Agata Mitera ◽  
Jerzy Jochem
Keyword(s):  
Receptor Antagonist ◽  
Cardiovascular Effects ◽  
Haemorrhagic Shock ◽  
Histaminergic System ◽  
Y1 Receptor

Synergistic Antiplatelet Effect of Ridogrel, a Combined Thromboxane Receptor Antagonist and Thromboxane Synthase Inhibitor, and UDCG-212, a cAMP-Phosphodiesterase Inhibitor

1993 ◽  
Vol 70 (05) ◽  
pp. 822-825 ◽  
Author(s):  
B Hoet ◽  
J Arnout ◽  
H Deckmyn ◽  
J Vermylen
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Receptor Antagonist ◽  
Phosphodiesterase Inhibitor ◽  
Camp Phosphodiesterase ◽  
Thromboxane Receptor ◽  
Thromboxane Synthase Inhibitor ◽  
Thromboxane Receptor Antagonist ◽  
Synthase Inhibitor ◽  
Camp Levels

SummaryRidogrel, a combined thromboxane receptor antagonist and thromboxane synthase inhibitor (1), inhibits platelet aggregation. Following stimulation with arachidonic acid, cAMP-levels are increased in human platelets preincubated with ridogrel, this is due to the known reorientation of the metabolism of the formed endoperoxides towards adenylate cyclase stimulating prostaglandins.Pretreatment of resting platelets with UDCG-212, a cAMP-phosphodiesterase inhibitor (2), also inhibits platelet aggregation induced by arachidonic acid, concomitant with an increase in cAMP levels, due to an inhibition of its breakdown. Under basal conditions, cAMP also is increased.By combining the two drugs, a more than additive action was observed on platelet aggregation and on both resting and stimulated platelet cAMP content. The appropriate combination may result in a more effective antiplatelet strategy.

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