On the mode of action of ergometrine in the isolated dog coronary artery

Sakanashi, Matao; Yonemura, K

doi:10.1016/0014-2999(80)90038-2

Cited by 29 publications

(8 citation statements)

References 9 publications

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“…These findings indicate that methysergide is a selective and noncompentive antagonist against serotonergic receptors in coronary artery. Moreover, this ergot derivative raised the resting tone in the concentration higher than 0.03 IM in accord with recent reports suggesting some agonist activity on coronary artery (Muller-Schweinitzer, 1980;Sakanashi and Yonemura, 1980). The agonist activity of the drug (0.3 MM) was 14 ± 4% of constrictor responses to equimolar concentration of serotonin (n = 5).…”

Section: Responses Of Carotid and Femoral Stripssupporting

confidence: 76%

“…Previous observations by Innes (1962) and Muller-Schweinitzer and Stunner (1974), indicating that ergonovine and ergotamine stimulate a-adrenergic receptors in isolated rabbit aortas and canine saphenous veins, are confirmed in this study and extended to carotid and femoral arteries of rabbits. Recent data suggest that ergonovine induces contraction of canine coronary arteries by stimulating serotonergic receptors (Muller-Schweinitzer, 1980;Sakanashi and Yonemura, 1980). The mechanism of ergonovine-induced contractions of rabbit arteries was defined by the use of specific antagonists.…”

Section: Discussionmentioning

confidence: 99%

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Hyperreactivity of coronary arterial smooth muscles in response to ergonovine from rabbits with hereditary hyperlipidemia.

Yokoyama¹,

Akita²,

Mizutani³

et al. 1983

Circulation Research

103

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SUMMARY. This study was undertaken to examine the response to ergonovine, an agent used to provoke spastic constriction of large epicardial coronary arteries, to elucidate the, responsible underlying mechanism, and to determine the impact of endogenous hyperlipidemia on contractile properties of isolated vessels from different beds. The isolated arteries from both control and Watanabe hereditary hyperlipidemic rabbits (WHHL rabbits) were suspended for recording isometric force in oxygenated Krebs buffer and exposed to agonists and antagonists. In atherosclerotic aortas from WHHL rabbits, the concentration-response relations for ergonovine and serotonin exhibited a marked leftward shift with significantly depressed constrictor threshold concentration and lowered one-half maximally effective concentration values. In coronary arteries with no atherosclerotic lesions detectable macroscopically from WHHL rabbits, the concentrationresponse relations showed a leftward shift for ergonovine but not for serotonin. Coronary contraction evoked by ergonovine was remarkably inhibited by 0.1 tiu cyproheptadine and 0.3 /iM methysergide, serotonergic antagonists, in both groups. a-Adrenergic blockade with 0.1 JZM prazosin was effective in inhibiting ergonovine-induced contraction of aortas from control rabbits, but not that of atherosclerotic ones. The constrictor response to ergonovine of atherosclerotic aortas was inhibited by cyproheptadine. The responsiveness to ergonovine of both carotid and femoral arteries from WHHL rabbits with no sclerotic lesions, which was suppressed by prazosin was not different from that of control rabbits. In contrast, the concentration-response relations for phenylephrine in the four different types of arteries did not differ appreciably between the two groups, and the constrictor responses to 20 ITIM KG were virtually identical. Thus, aortas and coronary arteries exposed to endogenous hyperlipidemia appear to be hyperreactive to ergonovine mediated by a serotonergic mechanism. (Circ Res 53: 63-71, 1983)

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Section: Responses Of Carotid and Femoral Stripssupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Hyperreactivity of coronary arterial smooth muscles in response to ergonovine from rabbits with hereditary hyperlipidemia.

Yokoyama¹,

Akita²,

Mizutani³

et al. 1983

Circulation Research

103

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“…In a similar study, however, McFadden et al (1991) included patients with Prinzmetal's angina (diagnosed previously by intracoronary challenge with ergometrine (ergonovine)) and found that intracoronary infusions of 5-HT caused spasm (zero flow) which was resistant to ketanserin (McFadden et al, 1992). Ketanserin does not prevent either ergometrineinduced ischaemia (Freedman et al, 1984) or spontaneous attacks of variant angina (De Caterina et al, 1984) in man and although ergometrine activates many different types of receptors including a-adrenoceptors , both it (Muller-Schweinitzer, 1980;Sakanashi & Yonemura, 1980;Brazenor & Angus, 1981;Holtz et al, 1982), and the antimigraine drug methysergide (Saxena, 1974;Brazenor & Angus, 1981), cause contractions via receptors other than a-adrenoceptors. Thus, in the dog isolated coronary artery, ergometrine was found to be a potent agonist at unspecified 5-HT receptors (Brazenor & Angus, 1981) whilst in the rabbit saphenous vein, ergometrine was demonstrated to be a potent 5-HT1-like receptor agonist (MacLennan & Martin, 1990).…”

Section: Introductionmentioning

confidence: 99%

Comparison of contractile responses to 5‐hydroxytryptamine and sumatriptan in human isolated coronary artery: synergy with the thromboxane A₂‐receptor agonist, U46619

Cocks

Kemp

Pruneau

et al. 1993

British J Pharmacology

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1 The interaction between the thromboxane A2 receptor agonist, U46619 and two 5-hydroxytryptamine (5-HT) receptor agonists, the non-selective, naturally occurring agonist, 5-HT and the selective 5-HT1-like agonist, sumatriptan were studied in human epicardial coronary arteries in vitro. 2 Coronary artery rings (2-4 mm in diameter) were prepared from epicardial arteries from explant hearts of patients undergoing heart transplant (cardiomyopathy, n = 13; ischaemic heart disease, n = 10) and unused donor hearts (n = 5). Each ring of artery was set at optimal resting conditions to record changes in isometric force. 3 The majority of artery rings developed phasic, rhythmic contractions either spontaneously or in response to all vasoconstrictor agonists tested. Both the spontaneous and agonist-induced phasic contractions were abolished by nifedipine (0.1 pM).4 Concentration-contraction curves to 5-HT-receptor agonists and noradrenaline (NA), were first constructed in artery rings that did not develop phasic activity. 5-HT and ergometrine were the most potent agonists with EC50 values of 6.8 ± 0.2 and 7.7 ± 0.2 (-log M) respectively. Potencies (EC50's) to sumatriptan, methylergide and noradrenaline could not be determined due to their poor ability to contract the coronary artery. Maximum contractions (Em,; normalized as a percentage of the contraction to a maximum-depolarizing concentration of K+ in physiological salt solution (KPSS)) for 5-HT, ergometrine, sumatriptan, methysergide and noradrenaline were 40 ± 10, 9 ± 3, < 5, < 5 and < 5% respectively. 5 In arteries without phasic activity, U46619 (1 nM) caused an increase in force of 3.8 ± 1% KPSS. With U46619 present, the Ema,, values for 5-HT, ergometrine, sumatriptan and methysergide were all markedly increased. For 5-HT and sumatriptan, E., values were 92± 4% and 49 ± 14% KPSS respectively. The presence of U46619 did not significantly change the sensitivity (EC50) to 5-HT. 6 In a separate series of arteries, nifedipine (0.1 tM) was used to block phasic, contractile activity. The synergy observed between U46619 and 5-HT or sumatriptan still occurred although the Em. values for each agonist were depressed but the EC50 values were again unaffected. 7 In conclusion, these in vitro studies indicate that the normally poor contractions to sumatriptan, in human coronary arteries are significantly enhanced when active force is induced with a thromboxane A2-receptor agonist, U46619. The enhanced response is not specific for either sumatriptan or 5-HT,-like receptors since contractions to 5-HT, ergometrine and methysergide were also potentiated by U46619.

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“…On the other hand, ergonovine is an ergot alkaloid and a potent vaosconstrictor that is used to test the susceptibility of patients to coronary vasospasm because this agent causes contraction of the smooth muscle mainly by activation of serotonergic receptors with little contribution of ·-adrenoceptors [25][26][27][28]. The use of intravenous ergonovine in the evaluation of coronary spasm is well established, although its accuracy and safety have been questioned.…”

Section: Different Effects Of Three Agonists On Contraction and Relaxmentioning

confidence: 99%

A Novel 5-HT<sub>2</sub> Antagonist, Sarpogrelate Hydrochloride, Shows Inhibitory Effects on Both Contraction and Relaxation Mediated by 5-HT Receptor Subtypes in Porcine Coronary Arteries

Gong¹,

Nakamura²,

Hattori³

et al. 2000

Pharmacology

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In isolated porcine coronary arteries, concentrations of 5-HT (10^–8 to 3 × 10^–5 mol/l), α-methylserotonin (α-Me-5-HT, 10^–8 to 3 × 10^–5 mol/l) and ergonovine (10^–9 to 3 × 10^–4 mol/l) produced contraction, whereas high concentrations (10^–5 to 10^–4 mol/l) of these drugs produced relaxation. Both sarpogrelate and ketanserin produced rightward shifts of contraction concentration-response curves induced by 5-HT and α-Me-5-HT at the concentration from 10^–9 to 3 × 10^–5 mol/l, and only sarpogrelate inhibited the relaxation at high concentrations of 5-HT and displayed 155% of maximal contraction at 10^–4 mol/l 5-HT. On the other hand, sarpogrelate and ketanserin did not show any inhibitory effects on the relaxation induced by high concentrations of ergonovine. These results suggested that sarpogrelate and ketanserin show different inhibitory effects on the relaxation induced by high concentrations of 5-HT, indicating that these two drugs may have different affinities to 5-HT receptor subtypes that may be involved in relaxation.

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On the mode of action of ergometrine in the isolated dog coronary artery

Cited by 29 publications

References 9 publications

Hyperreactivity of coronary arterial smooth muscles in response to ergonovine from rabbits with hereditary hyperlipidemia.

Hyperreactivity of coronary arterial smooth muscles in response to ergonovine from rabbits with hereditary hyperlipidemia.

Comparison of contractile responses to 5‐hydroxytryptamine and sumatriptan in human isolated coronary artery: synergy with the thromboxane A₂‐receptor agonist, U46619

A Novel 5-HT<sub>2</sub> Antagonist, Sarpogrelate Hydrochloride, Shows Inhibitory Effects on Both Contraction and Relaxation Mediated by 5-HT Receptor Subtypes in Porcine Coronary Arteries

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On the mode of action of ergometrine in the isolated dog coronary artery

Cited by 29 publications

References 9 publications

Hyperreactivity of coronary arterial smooth muscles in response to ergonovine from rabbits with hereditary hyperlipidemia.

Hyperreactivity of coronary arterial smooth muscles in response to ergonovine from rabbits with hereditary hyperlipidemia.

Comparison of contractile responses to 5‐hydroxytryptamine and sumatriptan in human isolated coronary artery: synergy with the thromboxane A2‐receptor agonist, U46619

A Novel 5-HT<sub>2</sub> Antagonist, Sarpogrelate Hydrochloride, Shows Inhibitory Effects on Both Contraction and Relaxation Mediated by 5-HT Receptor Subtypes in Porcine Coronary Arteries

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Comparison of contractile responses to 5‐hydroxytryptamine and sumatriptan in human isolated coronary artery: synergy with the thromboxane A₂‐receptor agonist, U46619