Hypertension exhibits 5-HT4 receptor as a modulator of sympathetic neurotransmission in the rat mesenteric vasculature

García-Pedraza, José Ángel; García-Domingo, Mónica; Gómez-Roso, Miriam; Ruiz-Remolina, Laura; Rodríguez-Barbero, Alicia; Martín, María Luisa; Morán, Asunción

doi:10.1038/s41440-019-0217-7

Cited by 4 publications

(3 citation statements)

References 44 publications

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“…As currently, no selective 5-HT 5A receptor agonist is described, to study this receptor type effect, we utilised a 5-HT 5A selective serotonergic antagonist (SB 699551) prior to 5-CT administration [ 25 ]. As SB 699551 did not reverse 5-CT inhibitory action, we could devoid 5-HT 5A receptor type of any sympatholytic effect in the kidney vasculature of diabetic animals and confirm that the sole serotonergic receptor type involved in the sympatho-inhibitory effect on vasopressor responses is the 5-HT 1 receptor type, which is in agreement with previous results by our group at vascular level in normoglycaemic and diabetic rats [ 21 , 22 ], and at renal or mesenteric levels in normoglycaemic rats [ 18 , 19 ], but differs from those obtained in the mesentery of hypertensive rats, where 5-HT 4 was the responsible receptor type of the serotonergic inhibitory effect [ 39 ].…”

Section: Discussionsupporting

confidence: 91%

“…exogenous NA are higher in diabetic than in normoglycaemic animals supports both the development of diabetic peripheral neuropathy and microvascular complications in the kidney [ 37 , 38 ]. Our group has already shown cardiovascular sympathetic overactivity as a marker of cardiovascular impairment in diabetes [ 22 , 25 , 26 ] or hypertension [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…The serotonergic system acts as modulator, both potentiating and inhibiting noradrenergic or vagal outflow at cardiac and vascular levels in different experimental models [ 21 , 22 , 23 , 24 , 40 , 41 ]. Furthermore, our group has described the serotonergic inhibitory action of noradrenergic input at mesenteric and renal levels [ 18 , 19 , 39 ]. Moreover, in diabetic animals, 5-HT is also able to reduce vasopressor responses to sympathetic stimulation in the kidney (current data).…”

Section: Discussionmentioning

confidence: 99%

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Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT1D Receptor Activation via NO Pathway

Fernández-González

García-Pedraza

Ordóñez

et al. 2023

IJMS

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Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in normoglycaemic rats. Considering that diabetes induces cardiovascular complications, we aimed to determine whether diabetic state modifies noradrenergic input at renal level and its serotonergic modulation in rats. Alloxan diabetic rats were anaesthetized (pentobarbital; 60 mg/kg i.p.) and prepared for in situ autoperfusion of the left kidney to continuously measure systemic blood pressure (SBP), heart rate (HR), and renal perfusion pressure (RPP). Electrical stimulation of renal sympathetic outflow induces frequency-dependent increases (Δ) in RPP (23.9 ± 2.1, 59.5 ± 1.9, and 80.5 ± 3.5 mm Hg at 2, 4, and 6 Hz, respectively), which were higher than in normoglycaemic rats, without modifying HR or SBP. Intraarterial bolus of 5-HT and 5-CT (5-HT1/5/7 agonist) reduced electrically induced ΔRPP. Only L-694,247 (5-HT1D agonist) reproduced 5-CT inhibition on sympathetic-induced vasoconstrictions, whereas it did not modify exogenous noradrenaline-induced ΔRPP. 5-CT inhibition was exclusively abolished by i.v. bolus of LY310762 (5-HT1D antagonist). An inhibitor of guanylyl cyclase, ODQ (i.v.), completely reversed the L-694,247 inhibitory effect. In conclusion, diabetes induces an enhancement in sympathetic-induced vasopressor responses at the renal level. Prejunctional 5-HT1D receptors, via the nitric oxide pathway, inhibit noradrenergic-induced vasoconstrictions in diabetic rats.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT1D Receptor Activation via NO Pathway

Fernández-González

García-Pedraza

Ordóñez

et al. 2023

IJMS

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Vascular sympathetic neurotransmission and its serotonergic regulation are modified by chronic fluoxetine treatment

García-Pedraza

López

Fernández-González

et al. 2021

Journal of Pharmacological Sciences

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Monoaminergic Receptors as Modulators of the Perivascular Sympathetic and Sensory CGRPergic Outflows

Marichal‐Cancino

González‐Hernández

Muñoz-Islas

et al. 2020

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: Blood pressure is a highly controlled cardiovascular parameter that normally guarantees an adequate blood supply to all body tissues. This parameter is mainly regulated by vascular peripheral resistance and is maintained by local mediators (i.e., autacoids), and by the nervous and endocrine systems. Regarding the nervous system, blood pressure can be modulated at central level by regulating the autonomic output. However, at peripheral level there exists a modulation by activation of prejunctional monoaminergic receptors in autonomic- or sensory-perivascular fibers. These modulatory mechanisms on resistance blood vessels exert an effect on the release of neuroactive substances from the autonomic or sensory fibers that modify blood pressure. Certainly, resistance blood vessels are innervated by perivascular: (i) autonomic sympathetic fibers (producing vasoconstriction mainly by noradrenaline release); and (ii) peptidergic sensory fibers [producing vasodilatation mainly by calcitonin gene-related peptide (CGRP) release]. In the last years, by using pithed rats, several monoaminergic mechanisms for controlling both the sympathetic and sensory perivascular outflows have been elucidated. Additionally, several studies have shown the functions of many monoaminergic auto-receptors and hetero-receptors expressed on perivascular fibers that modulate neurotransmitter release. On this basis, the present review: (i) summarizes the modulation of the peripheral vascular tone by adrenergic, serotoninergic, dopaminergic, and histaminergic receptors on perivascular autonomic (sympathetic) and sensory fibers, and (ii) highlights that these monoaminergic receptors are potential therapeutic targets for the development of novel medications to treat cardiovascular diseases (with some of them explored in clinical trials or already in clinical use).

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Hypertension exhibits 5-HT4 receptor as a modulator of sympathetic neurotransmission in the rat mesenteric vasculature

Cited by 4 publications

References 44 publications

Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT1D Receptor Activation via NO Pathway

Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT1D Receptor Activation via NO Pathway

Vascular sympathetic neurotransmission and its serotonergic regulation are modified by chronic fluoxetine treatment

Monoaminergic Receptors as Modulators of the Perivascular Sympathetic and Sensory CGRPergic Outflows

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