Serotonin and Blood Pressure Regulation

Watts, Stephanie W.; Morrison, Shaun F.; Davis, Robert P.; Barman, Susan M.

doi:10.1124/pr.111.004697

Cited by 321 publications

(296 citation statements)

References 397 publications

(321 reference statements)

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“…12 One interesting speculation is that 5-HT is able to penetrate the blood-brain barrier to modify central function, and this is supported by work published over 40 years ago. 36−38 5-HT itself may alter the permeability of the blood brain barrier and increase its own passage into the CNS.…”

Section: Mg)mentioning

confidence: 96%

“…Surprisingly, experimental efforts to elevate free, platelet poor plasma 5-HT chronically (7 days) actually lowered blood pressure in the deoxycorticosterone acetate (DOCA)-salt and sham rat, 11 and a similar chronic reduction in blood pressure stimulated by 5-HT has been observed in the spontaneously hypertensive rat. 12 Thus, instead of contributing to essential hypertension, the elevated levels of 5-HT observed in hypertensive patients may actually represent an adaptation to elevated blood pressure, an idea yet to be examined. The exact mechanism(s) of a 5-HT-induced fall in blood pressure are not yet fully understood, but important mechanistic observations have been made, primarily in the rat model and using a one week infusion of 5-HT.…”

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confidence: 99%

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One-Month Serotonin Infusion Results in a Prolonged Fall in Blood Pressure in the Deoxycorticosterone Acetate (DOCA) Salt Hypertensive Rat

Davis

Szasz

Garver

et al. 2012

ACS Chem. Neurosci.

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A 7-day infusion of serotonin (5-hydroxytryptamine, 5-HT) causes a sustained fall in elevated blood pressure in the male deoxycorticosterone acetate (DOCA)-salt rat. As hypertension is a long-term disease, we presently test the hypothesis that a longer (30 day) 5-HT infusion could cause a sustained fall in blood pressure in the established hypertensive DOCA-salt rat. This time period (∼4 weeks) was also sufficient to test whether 5-HT could attenuate the development of DOCAsalt hypertension. 5-HT (25 μg/kg/min; sc) or vehicle (Veh) was delivered via osmotic pump to (1) established DOCA-salt rats for one month, (2) Sprague− Dawley rats prior to DOCA-salt administration for one month, and blood pressure and heart rate measured telemetrically. On the final day of 5-HT infusion, free platelet poor plasma 5-HT concentrations were significantly higher in 5-HT versus Veh-infused rats, and mean arterial pressure was significantly lower in 5-HT-infused (135 ± 4 mmHg vs Veh-infused 151 ± 7 mmHg) established DOCA-salt rats. By contrast, 5-HT-infusion did not prevent the development of DOCA-salt hypertension (144 ± 7 mmHg vs Veh = 156 ± 6 mmHg). Isometric contraction of aortic strips was measured, and neither the potency nor maximum contraction to the alpha adrenergic receptor agonist phenylephrine (PE) or 5-HT were modified by infusion of 5-HT (established or preventative infusion), and maximum aortic relaxation to acetylcholine (ACh) was modestly but not significantly enhanced (∼15% improvement). This study demonstrates 5-HT is capable of lowering blood pressure in established DOCA-salt hypertensive rats over the course of one month in a mechanism that does not significantly modify or is dependent on modified vascular responsiveness. This finding opens the possibility that elevation of 5-HT levels could be useful in the treatment of hypertension. KEYWORDS: 5-HT, blood pressure, vascular reactivity, hypertension H ypertension is characterized by an elevation in arterial pressure, increased vascular resistance, cardiac hypertrophy, increased sympathetic nervous system tone, and altered renal function. 1 Despite the myriad of deleterious changes, the etiology of essential hypertension remains largely unknown. Interestingly, several lines of evidence suggest an important association between 5-HT and hypertension.5-HT is a vasoactive amine synthesized primarily in the enterochromaffin cells of the gastrointestinal tract, and the raphe nucleus in the central nervous system. 2−4 Free plasma 5-HT in both human and animal models of hypertension are elevated compared to normotensive human and animal controls. 5,6 5-HT receptor antagonists (5-HT 2A receptor antagonist ketanserin, 5-HT 2B receptor antagonist LY272015) lower blood pressure in select animal models of hypertension but are ineffective in others. 7−9 The arteries of hypertensive animals are hyperresponsive to the constrictor effects of 5-HT, and selective 5-HT reuptake inhibitors elevate blood pressure. 8−10 Collectively, this evidence suggests that elevated le...

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Section: Mg)mentioning

confidence: 96%

mentioning

confidence: 99%

One-Month Serotonin Infusion Results in a Prolonged Fall in Blood Pressure in the Deoxycorticosterone Acetate (DOCA) Salt Hypertensive Rat

Davis

Szasz

Garver

et al. 2012

ACS Chem. Neurosci.

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“…We will not present the data concerning the cardiovascular system, as an excellent review was published recently. 18 ■ EARLY SOURCE OF 5-HT: MATERNAL, EMBRYONIC, PLACENTAL ORIGINS? Presence of 5-HT, its receptors, and the serotonin transporter (SERT) in preimplantation embryos and the ability of 5-HTspecific pharmacological agents to interfere with development suggested that 5-HT functions at the earliest stages of development.…”

Section: −17mentioning

confidence: 99%

Life without Peripheral Serotonin: Insights from Tryptophan Hydroxylase 1 Knockout Mice Reveal the Existence of Paracrine/Autocrine Serotonergic Networks

Amireault

Sibon

Côté

2012

ACS Chem. Neurosci.

138

113

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Since its identification, 75 years ago, the monoamine serotonin (5-HT) has attracted considerable attention toward its role as a neurotransmitter in the central nervous system. Yet, increasing evidence, from a growing number of research groups, substantiates the fact that 5-HT regulates important nonneuronal functions. Peripheral 5-HT, synthesized by the enzyme tryptophan hydroxyase (Tph) in intestinal cells, was assumed to be distributed throughout the entire body by blood platelets and to behave as a pleiotropic hormone. A decade ago, generation of a mouse model devoid of peripheral 5-HT lead to the discovery of a second isoform of the enzyme Tph and also suggested that 5-HT might act as a local regulator in various organs. The objective of this review is to highlight the newly discovered functions played by the monoamine using the Tph1 KO murine model and to outline current findings that led to the discovery of complete serotonergic systems in unexpected organs. Within an organ, both the presence of local Tph enzymatic activity and serotonergic components are of particular importance as they support the view that 5-HT meets the criteria to be qualified as a monoamine with a paracrine/autocrine function.

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“…[7][8][9] Several reports by our research team [10][11][12] and others 3,[13][14][15] have found that alterations in vasocontraction induced by 5-HT were observed in patients with cardiovascular diseases as well as in those with diabetes. An accumulating body of evidence suggests that 5-HT plays a role in the development of diabetic complications.…”

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confidence: 99%

Effect of Long-Term Diabetes on Serotonin-Mediated Contraction in Carotid Arteries from Streptozotocin-Induced Diabetic Male and Female Rats

Watanabe

Matsumoto

Ando

et al. 2016

Biological & Pharmaceutical Bulletin

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An accumulating body of evidence suggests that males and females differ in vascular function in arteries under pathophysiological states. In this study, we tested whether there was a sex difference associated with serotonin (5-hydroxytryptamine, 5-HT)-mediated contraction in the carotid arteries of long-term streptozotocin (STZ)-induced diabetic rats [viz. 23 or 24 weeks after STZ (65 mg/kg, intravenously (i.v.)) injection starting at 8 weeks old of rats]. In the control group, the 5-HT-and high-K -induced contractions were greater in females than in males. In both sexes, treatment with STZ led to a decrease of 5-HT-induced contraction in carotid arteries compared to controls. In STZ-induced diabetic rats, the carotid arterial 5-HTinduced contraction was greater in female rats than in diabetic male rats. The high-K -induced contraction was greater in diabetic female rats than in either age-matched female controls or diabetic male rats. Expression of the 5-HT 2A receptor, which is the main receptor for 5-HT-induced contraction in rat carotid arteries, was similar among the four groups. These results suggest that decreased 5-HT-induced carotid arterial contraction is seen in both sexes under long-term STZ-induced diabetic conditions. Further, this reduction seems to be weaker in females than in males. This alteration of 5-HT-induced contraction may be partly associated with increased voltage-dependent Ca 2 channel activity.Key words carotid artery; contraction; serotonin; sex difference; streptozotocin Although women generally develop cardiovascular diseases several years later than men, this benefit may be diminished in diabetic individuals. The results of numerous epidemiological studies investigating the relationship between sex and the development of cardiovascular disease in diabetics have been inconsistent.1,2) Alterations in the responsiveness of blood vessels to various hormones and/or neurotransmitters in patients of both sexes with diabetes mellitus are well established. [3][4][5][6] However, there is confounding evidence of vascular function between diabetics of both male and females.The neurotransmitter serotonin [5-hydroxytriptamine (5-HT)] is an important factor that is involved in the regulation of several vascular functions, including blood flow, blood pressure, and vascular tone, in pathophysiological states. 7-9)Several reports by our research team [10][11][12] and others 3,[13][14][15] have found that alterations in vasocontraction induced by 5-HT were observed in patients with cardiovascular diseases as well as in those with diabetes. An accumulating body of evidence suggests that 5-HT plays a role in the development of diabetic complications. For example, sarpogrelate, an antagonist of the 5-HT 2A receptor, has beneficial effects against diabetic nephropathy, neuropathy, and diabetes-associated vascular dysfunction, including arterial stiffness and arteriosclerosis, in diabetic patients and animal models. [16][17][18][19] This relevant evidence suggests that the manipulation of 5-HT function c...

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Serotonin and Blood Pressure Regulation

Cited by 321 publications

References 397 publications

One-Month Serotonin Infusion Results in a Prolonged Fall in Blood Pressure in the Deoxycorticosterone Acetate (DOCA) Salt Hypertensive Rat

One-Month Serotonin Infusion Results in a Prolonged Fall in Blood Pressure in the Deoxycorticosterone Acetate (DOCA) Salt Hypertensive Rat

Life without Peripheral Serotonin: Insights from Tryptophan Hydroxylase 1 Knockout Mice Reveal the Existence of Paracrine/Autocrine Serotonergic Networks

Effect of Long-Term Diabetes on Serotonin-Mediated Contraction in Carotid Arteries from Streptozotocin-Induced Diabetic Male and Female Rats

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