The Effects of Platelet-Derived Contractile Agents on Human Digital Arteries

Rf, Moulds; Iwanov, V.; Medcalf, Robert L.

doi:10.1042/cs0660443

Cited by 27 publications

(10 citation statements)

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“…ent study shows that both serotonin and thromboxane A2 are released during aggregation of human platelets under the experimental conditions imposed, and that both contribute to the contractions they evoke in coronary rings; Moulds et al (21) reached similar conclusions with human digital arteries. The concentration of serotonin measured in the bath in our experiments is above the EC50 determined for the contraction to the monoamine.…”

Section: Discussionsupporting

confidence: 61%

Aggregating human platelets cause direct contraction and endothelium-dependent relaxation of isolated canine coronary arteries. Role of serotonin, thromboxane A2, and adenine nucleotides.

Houston¹,

Shepherd²,

Vanhoutte³

1986

J. Clin. Invest.

169

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Aggregating human platelets contract isolated rings of canine coronary artery without endothelium, but relax rings with intact endothelium. We performed experiments to identify the substances released from platelets responsible for these effects. The contraction in rings without endothelium was reduced by treating the platelets with the thromboxane synthetase inhibitor, dazoxiben, or treating the vessels with the thromboxane-receptor antagonist, SQ 29548. The serotonergic antagonist, methiothepin, also reduced the platelet-induced contraction. The combination of methiothepin plus dazoxiben or SQ 29548 caused a further inhibition. The endothelium-dependent relaxation to platelets during contractions evoked by prostaglandin F2. was nearly abolished by the ADP-and ATP-scavenger, apyrase. It was not inhibited by methiothepin, which antagonizes endothelium-dependent relaxations to serotonin. Thus, both serotonin and thromboxane A2 contribute to the direct activation of coronary smooth muscle by aggregating human platelets, whereas adenine nucleotides are the principal mediators of the endothelium-dependent relaxation.

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Section: Discussionsupporting

confidence: 61%

Aggregating human platelets cause direct contraction and endothelium-dependent relaxation of isolated canine coronary arteries. Role of serotonin, thromboxane A2, and adenine nucleotides.

Houston¹,

Shepherd²,

Vanhoutte³

1986

J. Clin. Invest.

169

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“…274 " 285 Ketanserin also partially inhibited cerebrospinal fluid-induced contractions of human cerebral arteries 283 and platelet-induced contractions of human digital arteries 281 in vitro. Intra-arterial infusion of ketanserin (50 ng/kg/min) prevented the vasoconstriction induced by intra-arterial infusion of serotonin in the forearm of seven healthy volunteers, but it did not influence the initial vasodilatation caused by serotonin.…”

Section: Peripheral Vascular Effects Evidence In Favor Of S 2 -Serotomentioning

confidence: 99%

Serotoninergic mechanisms in hypertension. Focus on the effects of ketanserin.

et al. 1988

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SUMMARY Aggregating platelets release serotonin, which induces contraction of most vascular smooth muscle by activation of Sj-serotoninergic receptors. Serotonin released in the circulation may contribute to the increase in peripheral resistance of hypertension as the responsiveness of blood vessels from hypertensive animals and humans to the vasoconstrictor action of the monoamine is augmented. The data obtained with the new antihypertensive agent ketanserin may favor that interpretation. Ketanserin is a selective S 2 -serotoniiiergic antagonist with additional ai-adrenergic blockmg properties. In humans, it has a terminal half-life of 12 to 25 hours and is eliminated predominantly by the liver. The hemodynamic profile of ketanserin is that of a vasodilator drug with actions on both resistance and capacitance vessels. On short-term intravenous administration, it lowers blood pressure in hypertensive patients with minimal reflex changes In cardiovascular function. When given orally long term to hypertensive patients, ketanserin causes a sustained reduction in arterial blood pressure, comparable to that obtained with either /3-adrenergic biockers or diuretics. Several studies have shown a greater efficacy in older (> 60 years of age) than in younger patients independent of starting pressure. Side effects mainly consist of dizziness, somnolence, and dry mouth, but they are usually not severe. The mechanism underlying the antihypertensive effect of ketanserin is unclear. It cannot be attributed to either S 2 -serotoninergic or a,-adrenergic blockade alone, but an interaction between the two effects appears to be required.

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“…The other major constrictor agent released by activated platelets is thromboxane A2, which is a short-lived derivative of arachidonic acid (Hamberg, Svensson & Samuelsson, 1975). In human arteries, 5-HT is at least as potent as thromboxane A2 in producing the contraction which follows the application of aggregating platelets (Moulds, Iwanov & Medcalf, 1984). Apart from a role in haemostasis, platelet activation and the release of 5-HT have been implicated in a number of cerebrovascular disorders.…”

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confidence: 99%

The role of membrane depolarization in the contractile response of the rabbit basilar artery to 5‐hydroxytryptamine.

Garland¹

1987

The Journal of Physiology

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SUMMARY1. 5-Hydroxytryptamine (5-HT, 10-1-10-M) depolarized and contracted smooth muscle cells (resting potential: -69 1 +0 9 mV, n = 112) in isolated cylindrical segments of the rabbit basilar artery.2. Simultaneous measurement of membrane potential and wall tension (n = 43, thirteen vessels) showed that the onset of 5-HT-induced depolarization coincided with the onset of smooth muscle contraction in the majority of cells studied. In addition, the onset of relaxation which followed the wash-out of 5-HT always preceded the onset of membrane repolarization by 52 + 8 s (n = 14).3. In 30 % of smooth muscle cells exposed to concentrations of 5-HT greater than 10-6 M, fast rhythmic depolarizations (amplitude 10-20 mV) were superimposed on the developing depolarization. Rhythmic membrane depolarization was always followed by rhythmic smooth muscle contraction, which peaked 2-4 s after the peak of the fast depolarization.4. Muscle contraction, but not depolarization, produced with concentrations of 5-HT greater than 10-7 M, was significantly increased by the removal of intimalendothelial cells.5. Smooth muscle depolarization recorded in the presence of increased extracellular K+ ( > 5-2 mM) preceded the onset of smooth muscle contraction. For a similar change in membrane potential produced with either increased extracellular K+ or 5-HT, the corresponding increase in arterial wall tension was always greater with 5-HT.6. The depolarization and contraction induced by 5-HT was markedly reduced or abolished if extracellular Na+ was totally replaced, isosmotically, with either sucrose or Tris at pH 7-4. Normal-sized contraction, but not depolarization, was recorded with 5-HT in Na+-free Tris solution at pH 8.7. These observations suggest that 5-HT-stimulated contraction in cerebrovascular smooth muscle is largely a result of mechanisms other than depolarization of the smooth muscle cell membrane which it produces. However, high concentrations of 5-HT ( >10-6 M) can stimulate additional depolarization, which has a faster time course and rhythmic nature. Discrete depolarizations of this type are responsible for initiating additional, phasic smooth muscle contractions.

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The Effects of Platelet-Derived Contractile Agents on Human Digital Arteries

Cited by 27 publications

References 0 publications

Aggregating human platelets cause direct contraction and endothelium-dependent relaxation of isolated canine coronary arteries. Role of serotonin, thromboxane A2, and adenine nucleotides.

Aggregating human platelets cause direct contraction and endothelium-dependent relaxation of isolated canine coronary arteries. Role of serotonin, thromboxane A2, and adenine nucleotides.

Serotoninergic mechanisms in hypertension. Focus on the effects of ketanserin.

The role of membrane depolarization in the contractile response of the rabbit basilar artery to 5‐hydroxytryptamine.

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