Recent advances in understanding serotonin regulation of cardiovascular function

Côté, Francine; Fligny, Cécile; Fromes, Yves; Mallet, Jacques; Vodjdani, Guilan

doi:10.1016/j.molmed.2004.03.007

Cited by 118 publications

(69 citation statements)

References 49 publications

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“…This reasoning was based on the idea that in the rat, 5-HT is largely, although not solely, a vasoconstrictor. The 5-HT 1B and 5-HT 2A receptors mediate contraction in arteries from normotensive rats (Hoyer et al, 2002;Côté et al, 2004;Kaumann and Levy, 2006;Villalón and Centurion, 2007). Endothelial cell 5-HT 2B receptors that mediate 5-HT-induced relaxation have been reported in the rat jugular vein (Ellis et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

5-Hydroxytryptamine Lowers Blood Pressure in Normotensive and Hypertensive Rats

Diaz

Thompson

et al. 2008

J Pharmacol Exp Ther

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Arterial hyper-responsiveness to 5-hydroxytryptamine (5-HT) is a hallmark of hypertension, and plasma levels of free 5-HT are elevated in hypertension. We hypothesized that chronic administration of 5-HT would cause blood pressure to 1) rise in normotensive rats and 2) rise significantly more in hypertensive rats. The deoxycorticosterone acetate (DOCA)-salt hypertensive and sham normotensive rat were used. Animals were implanted with minipumps that delivered 5-HT (or vehicle) at a rate of 25 g/kg/min for 7 days. Free plasma 5-HT was elevated significantly by this protocol. Within 48 h, mean arterial blood pressure measured telemetrically decreased in sham (106 Ϯ 2 to 83 Ϯ 2 mm Hg) and in DOCA-salt hypertensive (166 Ϯ 9 to 112 Ϯ 3 mm Hg) rats; vehicle did not change blood pressure in either group. Ganglionic blockade (hexamethonium) reduced blood pressure to a greater magnitude in DOCA vehicle-administered rats (peak fall arterial pressure, 91 Ϯ 14 mm Hg) compared with DOCA 5-HT-administered rats (40 Ϯ 6 mm Hg). Maximal acetylcholine-induced (NO-dependent) relaxation in phenylephrine-contracted aortic strips was greater in 5-HTadministered (69.2 Ϯ 9.1% relaxation) versus vehicle-administered (39.7 Ϯ 14.2%) DOCA rats; aortic endothelial cell nitric oxide synthase expression was higher in the 5-HT-versus vehicle-administered DOCA-salt rats. In normotensive and DOCAsalt hypertensive rats, the nitric oxide synthase (NOS) inhibitor N -nitro-L-arginine (0.5 g/l in water) prevented the fall in blood pressure to 5-HT. We conclude that chronic exogenous 5-HT reduces blood pressure in normotensive and hypertensive rats through mechanisms critically dependent on NOS.Serotonin [5-hydroxytryptamine (5-HT)] was discovered and characterized over 60 years ago by the Italian scientist Erspamer (Erspamer and Asero, 1952) and by Irving Page (Rapport et al., 1948; Page and McCubbin, 1953a,b). In the periphery, 5-HT is made primarily in the enterochromaffin cells of the intestine. The circulatory system is exposed to 5-HT through aggregation of platelets (which take up and store a millimolar concentration of 5-HT), release from adrenergic nerves that have taken up 5-HT, and through direct exposure to 5-HT that is free in the blood. In many tissues, 5-HT is taken up and concentrated by the serotonin transporter (SERT) and is rapidly metabolized to an inactive metabolite, 5-hydroxyindole acetic acid (5-HIAA), by intracellular monoamine oxidase.5-HT was originally described as a substance derived from serum (sero) that increased the tone of smooth muscle (tonin). Because of the close association of the platelet with the blood vessel, there has been a long-standing question as to the role of 5-HT in controlling vascular tone and modifying blood pressure under normotensive and hypertensive conditions. Several findings suggest that 5-HT contributes to systemic hypertension. These include the following findings: 1) plasma levels (free) of 5-HT are elevated in experimental and human models of hypertension (Fetkovska et al., 1990;Carr...

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Section: Discussionmentioning

confidence: 99%

5-Hydroxytryptamine Lowers Blood Pressure in Normotensive and Hypertensive Rats

Diaz

Thompson

et al. 2008

J Pharmacol Exp Ther

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“…We refer the reader to other reviews that cover different aspects of the CV system or that provide a more detailed historical perspective of 5-HT in the CV system: Kuhn et al, 1980;Marwood and Stokes, 1984;Docherty, 1988;Vanhoutte, 1991;van Zwieten et al, 1992;McCall and Clement, 1994;Yildiz et al, 1998;Nebigil and Maroteaux, 2001;Ramage, 2001;Doggrell, 2003;Côté et al, 2004;MaurerSpurej, 2005;Watts, 2005;Villalón and Centurión, 2007;Ramage and Villalón, 2008;Nalivaiko and Sgoifo, 2009;Nichols, 2009;Nigmatullina et al, 2009;Monassier et al, 2010;and Mercado et al, 2011. We will not discuss pulmonary blood pressure or pulmonary hypertension, but refer readers to an excellent review: MacLean and Dempsie, 2009.…”

Section: -Hydroxytryptamine (5-ht;mentioning

confidence: 99%

“…In humans and in animals, 5-HT predominantly causes direct arterial constriction, and the list of references here are just a few that report the effects of 5-HT in the isolated artery; more are included in the legend to Fig. 2: McGregor and Smirk, 1970;Docherty, 1988;Rosón et al, 1990;Vanhoutte, 1991;van Zwieten et al, 1992;Webb et al, 1992;Nishimura and Suzuki, 1995;Nishimura, 1996;Yildiz et al, 1996Yildiz et al, , 1998Boston and Hodgson, 1997;Watts, 1997Watts, , 2002Watts, , 2005Watts, , 2009HutriKähönen et al, 1999;Ramage, 2001;Janiak et al, 2002;Doggrell, 2003;Gul et al, 2003;Côté et al, 2004;Watts and Thompson, 2004;Villalón and Centurión, 2007;Ramage and Villalón, 2008;Nichols, 2009;and Nigmatullina et al, 2009. These studies have been performed in a variety of isolated blood vessels-basilar, superior mesenteric, aortic, femoral, mesenteric resistance, for example-such that constriction cannot be attributed to a single receptor type or size of vessel.…”

Section: -Hydroxytryptamine Synthesis and Handlingmentioning

confidence: 99%

“…The receptor mechanism for 5-HT to increase heart rate (positive chronotropy) is species-dependent. For example, this occurs through activation of 5-HT 2A receptors in the rat, 5-HT 4 receptors in the pig and human, and 5-HT 7 receptors in the cat (Saxena and Villalón, 1991;Villalón et al, 1997;Côté et al, 2004). In isolated cardiomyocytes, 5-HT stimulates mitogenesis, and the 5-HT 2B receptor is critical for development of the heart in the mouse (Nebigil and Maroteaux, 2001).…”

Section: -Hydroxytryptamine Presence and Function In The Heartmentioning

confidence: 99%

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Serotonin and Blood Pressure Regulation

et al. 2012

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“…Substantial data have demonstrated the existence of the neurohormonal model of HF progression [1] . Moreover, the important role of the serotonergic and sympatho-adrenal systems in the pathogenesis of HF has been well documented [2] . …”

mentioning

confidence: 99%