The modulatory role of vascular endothelium in the interaction of agonists and antagonists with α‐adrenoceptors in the rat aorta

Alosachie, Iyad; Godfraind, Théophile

doi:10.1111/j.1476-5381.1988.tb11684.x

Cited by 53 publications

(38 citation statements)

References 21 publications

(23 reference statements)

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“…L-NAME has been shown to inhibit the synthesis of NO in the endothelium (Rees et al, 1990;Pfeiffer et al, 1996), and such inhibition has been reported to enhance vascular smooth muscle contraction (Martin et al, 1986;Alosachie and Godfraind, 1988;Osugi et al, 1990;Kaneko and Sunano, 1993). We have also observed that EDR of the aorta and of the carotid and iliac arteries from L-NAME-treated rats was impaired (Sekiguchi et al, 2001).…”

Section: Discussionsupporting

confidence: 62%

Endothelium-Dependent Relaxation in Pulmonary Arteries of L-NAME-Treated Wistar and Stroke-Prone Spontaneously Hypertensive Rats.

Sekiguchi

Yamamoto

Matsuda

et al. 2002

J. Smooth Muscle Res.

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To evaluate whether the elevated blood pressure induced by chronic treatment with N ω -nitro-L-arginine methyl ester (L-NAME) contributes to an impairment of endotheliumdependent relaxation (EDR), the effects of chronic treatment of Wistar rats with L-NAME on systolic blood pressure, pulmonary arterial blood pressure and EDR of the pulmonary arteries were studied and compared with those of stroke-prone spontaneously hypertensive rats (SHRSP). While the systolic blood pressure (SBP) of Wistar rats was increased above that of controls by chronic treatment with L-NAME, it was still significantly lower than that of SHRSP. Chronic treatment with L-NAME did not affect pulmonary arterial blood pressure. On the other hand, the pulmonary arterial blood pressure of SHRSP was slightly but significantly higher than that of the control normotensive Wistar Kyoto rats (WKY). EDR in response to acetylcholine in the pulmonary artery of L-NAME-treated rats was significantly smaller than that in control Wistar rats. The EDR markedly increased in the presence of L-arginine and completely disappeared in the presence of N ω -nitro-L-arginine. Indomethacin hardly affected EDR. In preparations from SHRSP, the EDR was not different from that in those from WKY. Relaxation induced by sodium nitroprusside was identical in all preparations. Elevation of SBP and the impairment of EDR observed in L-NAME-treated rats recovered two weeks following cessation of treatment. These results suggest that the impaired EDR in the pulmonary artery of L-NAME-treated rats is not due to an L-NAME-induced increase in blood pressure but due to the inhibition of nitric oxide synthase by the drug remaining in the endothelium.

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Section: Discussionsupporting

confidence: 62%

Endothelium-Dependent Relaxation in Pulmonary Arteries of L-NAME-Treated Wistar and Stroke-Prone Spontaneously Hypertensive Rats.

Sekiguchi

Yamamoto

Matsuda

et al. 2002

J. Smooth Muscle Res.

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“…In some aspects, however, the present results could be compared with those recently published by Alosachie & Godfraind (1988) on the role of the vascular endothelium in the interaction of a-adrenoceptor agonists and antagonists in the rat aorta. These authors reported that xl-adrenoceptor antagonists acted as non-competitive antagonists against noradrenaline in the presence of endothelium and as competitive antagonists after endothelial cell removal.…”

Section: Discussionmentioning

confidence: 86%

“…In the present study, pirenzepine acted as a non-competitive antagonist against ACh in the presence of the endothelium and as a competitive antagonist when the endothelium was removed, while both AFDX 116 and pFHHSiD acted as competitive antagonists in arteries both with and without endothelium, although the pKB for pFHHSiD was underestimated in endothelium-intact preparations ( Figure 5). Alosachie & Godfraind (1988) Tschudi et al, 1991;Simonsen et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of muscarinic receptors in lamb isolated coronary resistance arteries

Simonsen

Prieto

Rivera

et al. 1993

British J Pharmacology

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1 In vitro experiments in a microvascular myograph were designed to characterize postjunctional muscarinic receptors producing contraction both in the presence and absence of the endothelium in coronary resistance arteries (normalized diameter of 150-450 jm), isolated from the left ventricle of hearts from 3-6 month old lambs. Preferential muscarinic receptor antagonists were used to determine the receptor subtype: pirenzepine (MI receptor), AFDX 116 (M2 receptor), 4-DAMP and pFHHSiD (M3 receptor). 2 The rank order of potency for muscarinic agonist-induced increases in tension in endothelium-intact preparations was oxotremorine-M = methacholine = acetylcholine (ACh) > carbachol. Removal of the endothelium increased the potency of ACh, but this procedure did not change either the sensitivity or maximal response to carbachol. 3 The contractile response to ACh was reproducible. Incubation with 3 x 10-7-3 x 10-6 M pirenzepine induced non-parallel rightward shifts and depressed the maximum of the concentration-response curve to ACh in endothelium-intact arteries. The slope by Schild analysis was 2.9 ± 0.8 (P <0.05, n = 7). Atropine, AFDX 116, 4-DAMP and pFHHSiD produced parallel rightward shifts of the curves to ACh and the slopes of the Schild plots were not significantly different from unity. The pKB values for the antagonists from plots constrained to unity in endothelium-intact segments were: atropine (9.4), 4-DAMP (9.0), pFHHSiD (7.9) and AFDX 116 (6.2). 4 In endothelium-denuded arteries, pirenzepine, AFDX 116 and pFHHSiD caused concentrationdependent, parallel rightward displacements of the concentration-response curves to ACh and the slopes of the Schild plots were not significantly different from unity. The plots constrained to a slope of unity gave the following pKB values: pFHHSiD (8.7), pirenzepine (7.5) and AFDX 116 (6.2). 5 In the presence of the endothelium, low concentrations of pirenzepine (10-9-1-' M) produced leftward shifts of the ACh concentration-response curves. This potentiating effect of pirenzepine was reversed by endothelial cell removal. In preparations precontracted with the thromboxane-mimetic, U46619, the putative MI-selective agonist, McN-A-343, induced a biphasic relaxation with log IC50 of 8.53 ± 0.14 and 5.02 ± 0.08 for the first and second phase of the relaxation, respectively, and maximal relaxations of 22.8 ± 4.3% and 41.1 ± 5.4% (n = 16). McN-A-343 relaxed the vessels in the presence of 10-' M pFHHSiD and 3 x 10-7 M AFDX 116, but not after incubation with 10-9 M pirenzepine.6 It is concluded from the pKB values for the antagonists used, that contraction induced by ACh in lamb coronary resistance arteries, in either the presence or the absence of the endothelium, is mediated via the M3 subtype of muscarinic receptors, while muscarinic receptors of another subtype at the endothelium seem to modulate the contractile response to ACh.

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“…The absolute change in isometric tension was greater in rat aortae denuded of endothelium. This has been shown (Martin et al, 1986) with other vasoconstrictors, such as a2-adrenoceptor agonists, and has been ascribed to a basal release of endothelium-derived relaxing factor (EDRF), which functionally antagonises constrictor responses (see Alosachie & Godfraind, 1988 for references). Warner et al (1988) have suggested that endothelin in the perfused rat mesenteric bed may release EDRF which could also account for the enhanced response in tissues denuded of endothelium.…”

Section: Discussionmentioning

confidence: 99%

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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The modulatory role of vascular endothelium in the interaction of agonists and antagonists with α‐adrenoceptors in the rat aorta

Cited by 53 publications

References 21 publications

Endothelium-Dependent Relaxation in Pulmonary Arteries of L-NAME-Treated Wistar and Stroke-Prone Spontaneously Hypertensive Rats.

Endothelium-Dependent Relaxation in Pulmonary Arteries of L-NAME-Treated Wistar and Stroke-Prone Spontaneously Hypertensive Rats.

Heterogeneity of muscarinic receptors in lamb isolated coronary resistance arteries

The pharmacological properties of the peptide, endothelin

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