Pharmacological evidence that histamine H3 receptors inhibit the vasodepressor responses by selective stimulation of the rat perivascular sensory CGRPergic outflow

Manrique-Maldonado, Guadalupe; Altamirano-Espinoza, Alain H.; Marichal‐Cancino, Bruno A.; Rivera‐Mancilla, Eduardo; Avilés-Rosas, Victor H.; Villalón, Carlos M.

doi:10.1016/j.ejphar.2015.02.017

Cited by 10 publications

(37 citation statements)

References 31 publications

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“…Our suggestion that peripheral H 3 receptors mediate the vago‐inhibitory action by histamine and methimepip is consistent with other findings implying that (i) central H 3 receptors modulate acetylcholine release in rat entorhinal cortex and (ii) peripheral H 3 receptors inhibit the muscarinic receptor‐activated calcium signalling in rat carotid body Type I cells . Similarly, other studies have shown that peripheral H 3 receptors inhibit (as heteroreceptors) (i) the vasodepressor sensory CGRPergic out‐flow and the vasopressor sympathetic out‐flow in rats, and (ii) the noradrenergic nerve‐mediated vasoconstriction and the CGRPergic nerve‐mediated vasodilatation in rat mesenteric arteries .…”

Section: Discussionsupporting

confidence: 92%

“…saline) did not significantly differ from the S-R curve in saline-treated animals, but it is not shown for the sake of clarity. R-(a)-methylhistamine induces endothelium-dependent vasodilatation in rat mesenteric arteries [40], but immepip (H 3 /H 4 receptor agonist) does not significantly change basal diastolic blood pressure and heart rate in pithed rats [21]. In our experiments, only i.v.…”

Section: Generalcontrasting

confidence: 52%

“…Moreover, regarding H 3 receptor activation, there are controversial data about its effect on blood pressure depending on the agonist used and the vascular bed under study. For example, R‐(α)‐methylhistamine induces endothelium‐dependent vasodilatation in rat mesenteric arteries , but immepip (H 3 /H 4 receptor agonist) does not significantly change basal diastolic blood pressure and heart rate in pithed rats . In our experiments, only i.v.…”

Section: Discussionmentioning

confidence: 47%

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Pharmacological Evidence that Histamine H₃ Receptors Mediate Histamine‐Induced Inhibition of the Vagal Bradycardic Out‐flow in Pithed Rats

García

García-Pedraza

Villalón

et al. 2015

Basic Clin Pharma Tox

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In vivo stimulation of cardiac vagal neurons induces bradycardia by acetylcholine (ACh) release. As vagal release of ACh may be modulated by autoreceptors (muscarinic M 2 ) and heteroreceptors (including serotonin 5-HT 1 ), this study has analysed the pharmacological profile of the receptors involved in histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats. For this purpose, 180 male Wistar rats were pithed, artificially ventilated and pre-treated (i.v.) with 1 mg/kg atenolol, followed by i.v. administration of physiological saline (1 ml/kg), histamine (10, 50, 100 and 200 lg/kg) or the selective histamine H 1 (2-pyridylethylamine), H 2 (dimaprit), H 3 (methimepip) and H 4 (VUF 8430) receptor agonists (1, 10, 50 and 100 lg/kg each). Under these conditions, electrical stimulation (3, 6 and 9 Hz; 15 AE 3 V and 1 ms) of the vagus nerve resulted in frequency-dependent bradycardic responses, which were (i) unchanged during the infusions of saline, 2-pyridylethylamine, dimaprit or VUF 8430; and (ii) dose-dependently inhibited by histamine or methimepip. Moreover, the inhibition of the bradycardia caused by 50 lg/kg of either histamine or methimepip (which failed to inhibit the bradycardic responses to i.v. bolus injections of acetylcholine; 1-10 lg/kg) was abolished by the H 3 receptor antagonist JNJ 10181457 (1 mg/kg, i.v.). In conclusion, our results suggest that histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats is mainly mediated by pre-junctional activation of histamine H 3 receptors, as previously demonstrated for the vasopressor sympathetic out-flow and the vasodepressor sensory CGRPergic (calcitonin gene-related peptide) out-flow.

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Section: Discussionsupporting

confidence: 92%

Section: Generalcontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 47%

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Pharmacological Evidence that Histamine H₃ Receptors Mediate Histamine‐Induced Inhibition of the Vagal Bradycardic Out‐flow in Pithed Rats

García

García-Pedraza

Villalón

et al. 2015

Basic Clin Pharma Tox

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“…Surprisingly, when exploring the cardiac sympatho‐inhibitory action of immepip (a histamine H 3 /H 4 receptor agonist) in diabetic (compared to normoglycaemic) pithed rats, we found that even at doses 1‐log unit higher (Figures D,E and B) than those in normoglycaemic rats (Figures B and A) failed to produce cardiac sympatho‐inhibition. Indeed, 3 and 10 μg/kg per minute immepip are high enough to interact with H 3 (but not H 4 ) prejunctional receptors modulating cardiovascular responses in normoglycaemic pithed rats . Hence, our findings suggest that, unlike in normoglycaemic rats, 3 the histamine H 3 /H 4 receptors do not play a cardiac sympatho‐inhibitory role in diabetic rats.…”

Section: Discussionmentioning

confidence: 61%

Differential cardiac sympatho‐inhibitory responses produced by the agonists B‐HT 933, quinpirole and immepip in normoglycaemic and diabetic pithed rats

Rivera‐Mancilla

Altamirano-Espinoza

Manrique-Maldonado

et al. 2018

Clin Exp Pharma Physio

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This study compared the cardiac sympatho-inhibitory responses produced by agonists at α -adrenergic (B-HT 933), dopamine D -like (quinpirole) and histamine H /H (immepip) receptors between normoglycaemic and streptozotocin-pretreated (diabetic) pithed rats. Intravenous (i.v.) continuous infusions of B-HT 933, quinpirole or immepip were used in normoglycaemic and diabetic pithed rats to analyse their sympatho-inhibitory effects on the electrically-stimulated cardioaccelerator sympathetic outflow. Both in normoglycaemic and diabetic animals, B-HT 933 (until 100 μg/kg per minute) and quinpirole (until 10 μg/kg per minute) inhibited the tachycardic responses to electrical sympathetic stimulation, but not those to i.v. bolus of exogenous noradrenaline. These sympatho-inhibitory responses were more pronounced in diabetic than in normoglycaemic animals. Accordingly, the areas under the curve for 100 μg/kg per minute B-HT 933 and 10 μg/kg per minute quinpirole in diabetic rats (1065 ± 70 and 920 ± 35, respectively) were significantly smaller (P < .05) than those in normoglycaemic rats (1220 ± 45 and 1360 ± 42, respectively). In contrast, immepip infusions produced cardiac sympatho-inhibition in normoglycaemic (until 10 μg/kg per minute), but not in diabetic (until 100 μg/kg per minute) animals. Our results suggest that in diabetic pithed rats: (i) the more pronounced cardiac sympatho-inhibition to B-HT 933 and quinpirole may be probably due to up-regulation of α -adrenergic and dopamine D -like receptors, respectively; (ii) the histamine H /H receptors do not seem to play a sympatho-inhibitory role; and (iii) there is a differential participation of α -adrenergic and dopamine D -like receptors, which may certainly represent therapeutic targets for the treatment of diabetic complications such as cardiovascular autonomic neuropathy.

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“…In this case, histamine plays a dual role on the CGRP release where prejunctional activation of H 3 receptors inhibits the neurogenic vasodilation [116, 117], whereas H 2 receptors enhance the CGRP nerve-mediated vasodilation possible by an enhancement of prejunctional activity of TRPV1 receptors [118]. In any case, these pro- and antivasodilator effects by the same molecule could reflect a fine tuning of the CGRP release by the sympathetic nerves.…”

Section: Cgrp and Vascular Tone Modulationmentioning

confidence: 99%

Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

González‐Hernández

Marichal‐Cancino

Lozano-Cuenca

et al. 2016

BioMed Research International

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Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide belonging to the calcitonin gene peptide superfamily. CGRP is a potent vasodilator with potential therapeutic usefulness for treating vascular-related disease. This peptide is primarily located on C- and Aδ-fibers, which have extensive perivascular presence and a dual sensory-efferent function. Although CGRP has two major isoforms (α-CGRP and β-CGRP), the α-CGRP is the isoform related to vascular actions. Release of CGRP from afferent perivascular nerve terminals has been shown to result in vasodilatation, an effect mediated by at least one receptor (the CGRP receptor). This receptor is an atypical G-protein coupled receptor (GPCR) composed of three functional proteins: (i) the calcitonin receptor-like receptor (CRLR; a seven-transmembrane protein), (ii) the activity-modifying protein type 1 (RAMP1), and (iii) a receptor component protein (RCP). Although under physiological conditions, CGRP seems not to play an important role in vascular tone regulation, this peptide has been strongly related as a key player in migraine and other vascular-related disorders (e.g., hypertension and preeclampsia). The present review aims at providing an overview on the role of sensory fibers and CGRP release on the modulation of vascular tone.

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Pharmacological evidence that histamine H3 receptors inhibit the vasodepressor responses by selective stimulation of the rat perivascular sensory CGRPergic outflow

Cited by 10 publications

References 31 publications

Pharmacological Evidence that Histamine H₃ Receptors Mediate Histamine‐Induced Inhibition of the Vagal Bradycardic Out‐flow in Pithed Rats

Pharmacological Evidence that Histamine H₃ Receptors Mediate Histamine‐Induced Inhibition of the Vagal Bradycardic Out‐flow in Pithed Rats

Differential cardiac sympatho‐inhibitory responses produced by the agonists B‐HT 933, quinpirole and immepip in normoglycaemic and diabetic pithed rats

Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

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Pharmacological evidence that histamine H3 receptors inhibit the vasodepressor responses by selective stimulation of the rat perivascular sensory CGRPergic outflow

Cited by 10 publications

References 31 publications

Pharmacological Evidence that Histamine H3 Receptors Mediate Histamine‐Induced Inhibition of the Vagal Bradycardic Out‐flow in Pithed Rats

Pharmacological Evidence that Histamine H3 Receptors Mediate Histamine‐Induced Inhibition of the Vagal Bradycardic Out‐flow in Pithed Rats

Differential cardiac sympatho‐inhibitory responses produced by the agonists B‐HT 933, quinpirole and immepip in normoglycaemic and diabetic pithed rats

Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

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Pharmacological Evidence that Histamine H₃ Receptors Mediate Histamine‐Induced Inhibition of the Vagal Bradycardic Out‐flow in Pithed Rats

Pharmacological Evidence that Histamine H₃ Receptors Mediate Histamine‐Induced Inhibition of the Vagal Bradycardic Out‐flow in Pithed Rats