Raynaud's Disease, Raynaud's Phenomenon, and Serotonin

Halpern, Alfred; Kühn, P; Shaftel, Herbert E.; Samuels, Saul S.; Shaftel, Norman; Selman, David; Birch, Herbert G.

doi:10.1177/000331976001100301

Cited by 83 publications

(17 citation statements)

References 37 publications

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“…Indeed, our thermographic studies showed that digital skin flow was increased by ketanserin, presumably by opening of arteriovenous shunts, which are densely innervated by sympathetic nerves" and possibly also by serotonergic fibers. 20 It is worth mentioning that forehead skin flow, as estimated by skin temperature measurements, was not increased by ketanserin. This contrasts with the rise of forehead temperature after hydralazine.…”

Section: Discussion Cardiovascular and Hormonal Effects Of Ketanserinmentioning

confidence: 88%

5-HT, alpha-adrenoceptors, and blood pressure. Effects of ketanserin in essential hypertension and autonomic insufficiency.

Wenting¹,

Woittiez²,

Veld³

et al. 1984

Hypertension

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SUMMARY The serotonin (5-hydroxytryptamine, 5-HT) antagonist, ketanserin, has a high affinity for 5-HT 2 -receptors but it also binds to a^adrenoceptors. The compound (10 mg i.v.) lowered mean arterial pressure by 22% ± 2% (mean ± SEM, p < 0.001) in 30 patients with essential hypertension. Measurements of heart rate, cardiac output, cardiac filling pressures, forearm blood flow, renal blood flow, and glomerular filtration rate revealed a hemodynamic pattern compatible with vasodilation of both resistance and capacitance vessels. This was accompanied by moderate reflex cardiostimulation. Ketanserin did not alter the pressor effect of bolus injections of (-)-phenylephrine hydrochloride ( A LTHOUGH 5-hydroxytryptamine (5-HT, serotonin) was among the first vasoactive amines . to be discovered and synthesized, its function in blood pressure regulation is still unclear. Recently, a differentiation between two subtypes of 5-HT-receptors has been made on the basis of radioligand-binding studies using membranes prepared from rat frontal cortex.1 Although specific functions associated with these brain receptors have not been identified, it has been shown that the 5-HT-receptors subserving contraction of vascular smooth muscle cells are of the 5-HT 2 -subtype. for clinical investigation. 4 " 6 Ketanserin, however, is not fully specific for 5-HT 2 -receptors, since it also binds to a,-adrenoceptors. High concentrations of ketanserin have an antagonistic effect on a,-adrenoceptor-mediated contractions of isolated arteries and veins. 4 Experiments in animals 4 and preliminary data in humans 8 9 have shown that ketanserin has antihypertensive properties. This may, at least in part, depend on blockade of a,-adrenoceptors. Indeed, it has been reported that hypotensive doses of ketanserin abolished the pressor response to a,-agonists in the pithed rat, the anesthetized normotensive rat, and the conscious spontaneously hypertensive rat.10 " This paper describes the hemodynamic profile of ketanserin's antihypertensive action in patients with essential hypertension. The possibility that the antihypertensive effect of ketanserin depends on interference with a,-adrenoceptor-mediated vasoconstriction was tested by comparison of the pressor effects of the a,-adrenoceptor agonist, phenylephrine, before and after ketanserin and by assessment of the antihypertensive effect of ketanserin after administration of the a,-adre-

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Section: Discussion Cardiovascular and Hormonal Effects Of Ketanserinmentioning

confidence: 88%

5-HT, alpha-adrenoceptors, and blood pressure. Effects of ketanserin in essential hypertension and autonomic insufficiency.

Wenting¹,

Woittiez²,

Veld³

et al. 1984

Hypertension

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“…Indeed, the intravenous injection of 5-HT into a finger vein in man produces venoconstriction [120], while direct infusion into the brachial artery causes a rapid drop in digital temperature and characteristic colour changes [121]. The former effect can be inhibited by ketanserin pretreatment [120].…”

Section: Clinical Evidencementioning

confidence: 99%

Platelet-vessel wall interactions: Implication of 5-hydroxytryptamine. A review

Clerck¹,

Nueten

Reneman³

1984

Agents and Actions

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The evidence for an impact of platelet-derived 5-hydroxytryptamine (5-HT) on local tissue perfusion is reviewed. By interacting with 5-HT2 serotonergic receptors, 5-HT, directly or through amplification, activates platelets, endothelial and vascular smooth muscle cells producing platelet aggregation, vascular permeability increase and large vessel constriction. Pharmacodissection in experimental animals with selective serotonergic 5-HT2 receptor antagonists, e.g. ketanserin, shows that 5-HT largely contributes to the platelet-mediated increase in vascular permeability, to platelet-vessel wall interaction during hemostasis, to cardiopulmonary dysfunction provoked by thromboembolism and to the platelet-mediated inhibition of peripheral collateral circulation. Clinical results obtained with ketanserin further substantiate an involvement of platelet-derived 5-HT in the pathogenesis of impaired tissue perfusion in some cardiovascular conditions.

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“…Support for this theory is derived from Lewis' experiments demonstrating that vasospastic attacks could be induced in fingers with acute sympathetic nerve blockade. Halpern and coworkers [3] were also able to produce attacks in limbs during sympathetic ganglionic blockade. Lewis' demonstration in 1929 that attacks could be induced by proximal cooling of the finger with the distal finger warm, and that the disappearance of attacks occurred only when the finger was warmed proximally and not distally [4], implicates an abnormality at the digital artery and not at the arteriolar level.…”

Section: Pathogenesismentioning

confidence: 96%

Pathogenesis and treatment of Raynaud's phenomenon

Coffman

1990

Cardiovasc Drug Ther

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The pathogenetic theories and treatment of Raynaud's phenomenon are reviewed. In primary Raynaud's disease, most evidence supports a local defect at the digital artery level, with vasoconstriction or vasospasm of the digital arteries inducing the color changes. Normal sympathetic activity, low transmural arterial distending forces, and serotonin may be associated factors in the production of vasospastic attacks. In Raynaud's phenomenon, persistent vasoconstriction, thickened vessel walls, increased blood viscosity, and low digital artery blood pressure distal to obstructions may lead to vasospastic attacks with normal sympathetic nerve stimuli. Since the underlying cause of primary Raynaud's disease is unknown, treatment involves the use of agents to reduce sympathetic nerve activity or to prevent vascular smooth muscle contraction. Most patients will respond to conservative measures, but if they fail nifedipine is the drug of choice and alleviates the syndrome in about two thirds of patients. Reserpine and guanethidine may be as effective, but well-controlled studies have not been performed. The beneficial response to prazosin is moderate and dissipates with time. Side effects with these drugs prevent their use in many patients. Diltiazem and nitroglycerin ointments are of questionable value. Ketanserin, a serotonergic S2-receptor antagonist, which has been shown to decrease the frequency of vasospastic attacks, and parenteral prostacyclin are among the new promising therapies.

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Raynaud's Disease, Raynaud's Phenomenon, and Serotonin

Cited by 83 publications

References 37 publications

5-HT, alpha-adrenoceptors, and blood pressure. Effects of ketanserin in essential hypertension and autonomic insufficiency.

5-HT, alpha-adrenoceptors, and blood pressure. Effects of ketanserin in essential hypertension and autonomic insufficiency.

Platelet-vessel wall interactions: Implication of 5-hydroxytryptamine. A review

Pathogenesis and treatment of Raynaud's phenomenon

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