Endothelin and Ca++ agonist bay K 8644: Different vasoconstrictive properties

Auguet, Michel; Delaflotte, Sylvie; Chabrier, Pierre‐Etienne; Pirotzky, E.; Clostre, F; Braquet, P.

doi:10.1016/s0006-291x(88)80822-2

Cited by 133 publications

(32 citation statements)

References 11 publications

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“…Furthermore, responses to endothelin were not enhanced by elevating the extracellular K+ concentration, a procedure shown (Schramm et al, 1988) to be essential in detecting vascular response to Bay K 8644 in vitro. Auguet et al (1988) have demonstrated a small but significant potentiation of the responses to endothelin in the rat aorta under similar conditions, but this was not confirmed in the present study. In agreement with other workers (see Introduction), the responses to endothelin were potently antagonised by calcium entry blockers, irrespective of their class, but no direct interaction was observed in radioligand binding studies.…”

Section: Discussioncontrasting

confidence: 99%

“…The high dependency of the responses to endothelin on extracellular calcium is in agreement with other groups (Yanigisawa et al, 1988;Hirata et al, 1988;Hughes et al, 1988) but in contrast to the findings of Auguet et al (1988). However, it appears to act at a different site to that of Bay K 8644 in this tissue.…”

Section: Discussionsupporting

confidence: 91%

“…The potency of endothelin in the endotheliumdenuded aorta of the rat observed in the present study (-log EC50 = 8.2) was less than observed in the pig coronary artery (-log EC50 = 9.40;Yanagisawa et al, 1988), but similar to values obtained in the rat isolated renal artery (-log EC50 = 8.76; Tomobe et al, 1988), aorta (-log EC50 = 8.39; Auguet et al, 1988) and human omental artery (-log EC50 = 8.55;Hughes et al, 1988 The responses to endothelin in the perfused mesenteric bed were different from those in other vascular studies, in that the absolute vasoconstriction was much greater than that observed to either phenylephrine or KCI. In the present study, the basal perfusion pressure was 40 mmHg, which was higher than has been employed in previous studies with this preparation (10mmHg, Randall et al, 1988).…”

Section: Discussionsupporting

confidence: 76%

“…Secondly, a series of experiments was conducted in which the concentration of KCI was increased from 4.6 x 10-3M to 1.5 x 10-2 K whilst NaCl was correspondingly decreased from 0.154M to 0.139M to retain equivalent osmotic tension. This method has been shown to partially depolarise the vascular smooth muscle and be a prerequisite for eliciting contractions to the dihydropyridine calcium facilitator, Bay K 8644 (Schramm et al, 1983;Auguet et al, 1988).…”

Section: Isolated Tissuesmentioning

confidence: 99%

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The pharmacological properties of the peptide, endothelin

Eglen¹,

Michel²,

Sharif³

et al. 1989

British J Pharmacology

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1 The effect of endothelin (ET-1) has been studied on isolated vascular and non-vascular preparations, using both functional and competition radioligand binding techniques. The effects of endothelin on blood pressure were studied in both anaesthetised, chemically denervated normotensive and spontaneously hypertensive rats (SHR). 2 Endothelin elicited contractile responses in the rat thoracic aorta, perfused mesenteric bed, rabbit mesenteric artery and portal vein. The maximal responses in the rat aorta were enhanced by removal of the endothelium, and were reduced in the presence of either a cyclo-oxygenase inhibitor (indomethacin) or a thromboxane receptor antagonist (SQ 29,548). In terms of potency, the most sensitive preparation was the rat endothelium-denuded aorta and rat perfused mesenteric bed (-log EC50 values = 8.2 + 0.07 and 8.2 + 0.12, mean + s.e.mean, n = 4, respectively). In the perfused mesenteric bed of the rat the maximum response to endothelin (219 + 12 mmHg, n = 4) was greater than that to either phenylephrine (maximal response = 67 + 9 mmHg; n = 4) or KCl (maximal response = 110 + 6 mmHg, n = 4).3 Endothelin elicited contractile responses of the guinea-pig isolated ileum, oesophageal muscularis mucosae and uterus. Responses were also observed in the rat fundic strip and paced left atria. The guinea-pig urinary bladder, trachea, rat vas deferens and anococcygeus exhibited little or no response to endothelin at the concentrations studied (1 x 10 -2-3.2 x 10 -8M). Of the above preparations, the ileum and oesophageal muscularis mucosae were the most sensitive to endothelin (-log EC50 = 8.5 + 0.11 and 8.4 + 0.06, n = 6, respectively), exhibiting potencies similar to those observed in the endothelium-denuded aorta of the rat. 4 In competition-radioligand binding studies, endothelin did not displace either [3H]-PN 210-100 or [125I]< -)-co-conotoxin GVIA from binding sites in membranes from rat cerebral cortex and, skeletal muscle or from guinea-pig cerebral cortex and hippocampus, respectively. This indicates a lack of direct interaction of endothelin at the dihydropyridine binding site and the N-type calcium channel, respectively. However, in functional studies, contractile responses to endothelin (1 x 10-8M) in the endothelium-denuded aorta of the rat were potently reversed by nifedipine, verapamil, and prenylamine (-log IC50 values = 8.0 + 0.13, 7.2 + 0.09 and 6.6 + 0.08, n = 4-8,

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 76%

Section: Isolated Tissuesmentioning

confidence: 99%

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The pharmacological properties of the peptide, endothelin

Eglen¹,

Michel²,

Sharif³

et al. 1989

British J Pharmacology

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“…After the original discovery ) the suggestion was made that endothelin may act as an endogenous direct activator of dihydropyridine-(Ltype) voltage-sensitive Ca channels in both vascular, tracheobronchial and cardiac mucle (Ishikawa et al, 1988a,b;Uchida et al, 1988;Tomobe et al, 1988). However, in some smooth muscles, the contractile response to endothelin is largely or totally resistant to dihydropyridine type Ca channel blockers (Auguet et al, 1988;Maggi et al, 1989a,b). Here we confirm that the response to this peptide in the human bladder muscle is nifedipine-resistant and also substantially unaffected by Bay K 8644.…”

Section: Discussionmentioning

confidence: 99%

Multiple sources of calcium for contraction of the human urinary bladder muscle

Maggi

Giuliani

Patacchini

et al. 1989

British J Pharmacology

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1 KC1, carbachol, neurokinin A and endothelin produced concentration-dependent contractions of mucosa-free muscle strips from the dome of the human urinary bladder. The maximal response to carbachol or neurokinin A exceeded that to KCI, while the maximal response to endothelin approached that to KCI.2 Nifedipine (1 gM) abolished the response to KCI, reduced the response to carbachol or neurokinin A but had no effect on the response to endothelin. Bay K 8644 (1 gM) markedly potentiated the response to KCl but had little or no effect on the response produced by the other stimulants. 3 Superfusion of the strips with a nominally calcium (Ca)-free medium containing EDTA (1 mM) for 30min markedly reduced the response to carbachol, neurokinin A and endothelin, although a small response was still evident at high concentrations. Likewise, after a prolonged (60min) superfusion of the strips with a high K (80mM) Ca-free medium plus EDTA (1 mM) these three agonists still produced a small contractile response.4 The nifedipine (1 gM) resistant response to carbachol, neurokinin A or endothelin was markedly depressed by LaCl3 (1 mM). In contrast, the nifedipine-(1 gM) resistant response to carbachol was not modified by NiCl2 (0.1 mM) or co-conotoxin (0.1 Mm). 5 Caffeine produced divergent effects depending upon the temperature of incubation: a relaxation at 370C-and a concentration-dependent (2.5-20mM) contraction at 250C. The latter was markedly inhibited by procaine (3mM) but unaffected by nifedipine (1 gM).6 After a prolonged (60 min) superfusion with a high K, Ca-free medium containing EDTA the response to carbachol (100 Mm) was abolished by previous exposure to procaine (3mM). Conversely, the response to endothelin (1 MM) was unaffected by procaine. The response to endothelin in these experimental conditions was also resistant to LaCl3 (1 mM).7 These findings indicate that multiple sources of Ca age mobilized for contraction of the human bladder muscle by different stimulants. Dihydropyridine-and voltage-sensitive Ca channels provide the major if not the sole source of Ca for the response to KCI, play some role in the response to muscarinic (carbachol) or NK-2 tachykinin receptor stimulation but are not involved in the response to endothelin. Carbachol, neurokinin A and endothelin all mobilize a Ca pool (either extracellular or located at membrane level) which is LaCl3-sensitive but nifedipine-resistant. Neither T-nor N-type channels appear to be involved in the response to carbachol. In addition, these agents mobilize a tightly bound Ca pool independently from membrane depolarization. This latter pool is probably a procaine-sensitive intracellular source of activator Ca mobilized by caffeine and carbachol. The failure of procaine to prevent the response to endothelin in high K, Ca-free medium raises the possibility that this peptide mobilizes an intracellular source of activator Ca, distinct from the caffeine-and carbachol-sensitive pool.

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Actions of endothelin‐1,2, and 3 in the microvasculature of bone

Briggs

Wood

1998

Journal Orthopaedic Research

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Endothelins have recently been associated with hypoxia-related vascular smooth-muscle constriction and with the so-called no-reflow phenomenon following reperfusion. Their action is tissue dependent. The role of endothelins on vascular smooth muscle in bone is unknown. An ex vivo perfusion model was used to investigate the effects of the three different endothelins on the vascular resistance in the canine tibia. Endothelin-1 and endothelin-2 had molar potencies similar to that of norepinephrine, whereas endothelin-3 was less potent. Tachyphylaxis to the same dose of endothelin-1 did not occur. The calcium channel blocker, diltiazem, attenuated (45% reduction) the vasoconstrictor responses to norepinephrine (p < 0.005) but had a smaller effect (24% reduction) on the responses to endothelin (p < 0.025). Vascular smooth muscle in bone appears to have endothelin receptors that are similar to those in other organs.

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Endothelin and Ca++ agonist bay K 8644: Different vasoconstrictive properties

Cited by 133 publications

References 11 publications

The pharmacological properties of the peptide, endothelin

The pharmacological properties of the peptide, endothelin

Multiple sources of calcium for contraction of the human urinary bladder muscle

Actions of endothelin‐1,2, and 3 in the microvasculature of bone

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