Chronic Serotonergic Blockade with Ketanserin in the Spontaneously Hypertensive Rat

Pettersson, Anders; Gradin, K.; Hedner, Thomas; Henning, Martina; Persson, Bengt

doi:10.1097/00005344-198500077-00032

Cited by 6 publications

(4 citation statements)

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“…The dopamine D 2 /D 3 agonist quinpirole after intrave-nous administration also results in profound increases in the baroreflex gain (47). That 5-HT does not directly affect baroreflex gain is suggested by reports that neither acute nor chronic administration of fluoxetine (a selective 5-HT reuptake inhibitor) nor administration of ketanserin (a 5-HT 2 receptor antagonist) nor intra-NTS microinjection of 5-HT change the sensitivity of the reflex arc (1,13,31,33,43). The mechanism of action of PEA in effecting autonomic changes remains unknown, although an inhibition of the reuptake, as well as effects on direct release of DA, NE, and possibly 5-HT, has been suggested (3,24,34).…”

Section: Discussionmentioning

confidence: 99%

Increased baroreceptor response in mice deficient in monoamine oxidase A and B

Holschneider

Scremin

Roos

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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The recent development of mice doubly deficient for monoamine oxidase A and B (MAO-A/B, respectively) has raised questions about the impact of these mutations on cardiovascular function, in so far as these animals demonstrate increased tissue levels of the vasoactive amines serotonin, norepinephrine, dopamine, and phenylethylamine. We recorded femoral arterial pressures and electrocardiograms in adult MAO-A/B-deficient mice during halothane-nitrous oxide anesthesia as well as 30 min postoperatively. During both anesthesia and recovery, systolic, diastolic, and mean arterial pressures were 10-15 mmHg lower in MAO-A/B-deficient mice compared with normal controls (P < 0.01). Mutants also showed a greater baroreceptor-mediated reduction in heart rate in response to hypertension after intravenous pulses of phenylephrine or angiotensin II. Tachycardia elicited in response to hypotension after nitroprusside was greater in mutants than in controls. Heart rate responsiveness to changes in arterial pressure was abolished after administration of glycopyrrolate, with no differences in this phenomenon noted between genotypes. These data suggest that prevention of hypertension may occur in chronic states of catecholaminergic/indoleaminergic excess by increased gain of the baroreflex.

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Section: Discussionmentioning

confidence: 99%

Increased baroreceptor response in mice deficient in monoamine oxidase A and B

Holschneider

Scremin

Roos

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…Typically the response is triphasic: a short-lasting depressor effect (resulting from the Bezold-Jarisch reflex), a pressor response, and finally a depressor action (164,197 185,190,206,208,209,[211][212][213]265,296). Higher doses are required in normotensive than in hypertensive animals to achieve smaller reductions in aortic blood pressure (265).…”

Section: Hypertensionmentioning

confidence: 99%

“…This central effect of ketanserin is best explained by its inhibitory action at central (Y I -adrenoceptors. In spontaneously hypertensive rats central mechanisms probably do not contribute to the hypotensive action of ketanserin (208,209).…”

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confidence: 99%

“…) blocking activity (3 1,32,90,134,135), although S2-serotonergic inhibition may contribute (101,267). The finding that in rats chronically treated with oral ketanserin the pressor response to phenylephrine is not attenuated indicates that the longterm hypotensive effect of ketanserin in these rats is not directly related to an aadrenoceptor blockade (208,209). In all animal species studied, the blood pressure lowering effect of ketanserin under acute conditions is not accompanied by an increase in heart rate despite the occurrence of peripheral vasodilation.…”

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confidence: 99%

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Ketanserin

Nueten

Janßen

Symoens

et al. 1987

Cardiovascular Drug Reviews

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Serotonin and Serotonin Antagonism in Cardiovascular and Non‐Cardiovascular Disease

Frishman

Huberfeld

Okin

et al. 1995

The Journal of Clinical Pharma

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Serotonin, or 5-hydroxytryptamine, is a naturally-occurring vasoactive substance found primarily in the brain, enterochromaffin tissue, and blood platelets. It has diffuse cardiophysiologic effects. The multiple effects of serotonin on blood vessels can be explained by the existence of 2 serotonergic receptor subtypes (the S1 receptor mediates vasodilation, and the S2 receptor vasoconstriction). Serotonin via the S2 receptor also augments the actions of several other vasoconstricting substances. Serotonin may be responsible for causing, or at least perpetuating, some forms of systemic hypertension through peripheral and central nervous system (CNS) actions. Ketanserin is a highly selective S2-serotonergic antagonist with additional alpha-adrenergic blocking activity, which has been proposed as a therapy for various cardiovascular diseases including hypertension. It has been shown to be more effective than placebo in treating hypertension and comparable in effectiveness to other antihypertensive drugs. Its major side effects relate to the CNS, and prolongation of the electrocardiogram QT interval has been described. Caution must be used when using ketanserin in patients receiving potassium- and magnesium-losing agents, because of the risk of torsades de pointes. Ketanserin has potential utility in the treatment of eclampsia, peripheral vascular disease, carcinoid syndrome, and "shock lung." The drug is not yet approved for clinical use in the United States.

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Chronic Serotonergic Blockade with Ketanserin in the Spontaneously Hypertensive Rat

Cited by 6 publications

References 0 publications

Increased baroreceptor response in mice deficient in monoamine oxidase A and B

Increased baroreceptor response in mice deficient in monoamine oxidase A and B

Ketanserin

Serotonin and Serotonin Antagonism in Cardiovascular and Non‐Cardiovascular Disease

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