Role of endothelium in the contractile response of rat aorta to α-adrenoceptor agonists

Godfraind, Théophile; Eglème, Cécile; Osachie, I Al

doi:10.1042/cs068s065

Cited by 108 publications

(68 citation statements)

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“…The pD2 NA values for these compounds for a,-adrenoceptors are presented in Table 1 together with isomeric activity ratios. The pD2 value for rat aorta with endothelium removed of8.30 for NA is in excellent agreement with the value of 8.17 obtained by Godfraind et al (1985).…”

Section: Methodssupporting

confidence: 78%

“…The thoracic aorta were removed and sectioned into 2 mm rings from which the endothelium was removed by mechanical rubbing. This procedure shifts the concentration-response curves of NA and phenylephrine to the left and increases maximum attainable tension (Godfraind et al, 1985). The rings were then suspended in a Krebs bicarbonate solution at 37°C under 1.5 g tension for 1 hour and allowed to equilibrate before examining the contractile response.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

Brown¹,

McGrath

Midgley

et al. 1988

British J Pharmacology

100

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1 The activities of the (-)-and (+ )-forms of m-and p-octopamine and m-and p-synephrine on a,-adrenoceptors from rat aorta and anococcygeus and a2-adrenoceptors from rabbit saphenous vein were compared with those of noradrenaline (NA).2 The rank order of potency of the (-)-forms on cx,-adrenoceptors from rat aorta and a2-adrenoceptors was NA > m-octopamine = m-synephrine > p-octopamine = p-synephrine. The two m-compounds were 6 fold less active than NA on x,-adrenoceptors from rat aorta and 150 fold less active on x,-adrenoceptors. The two p-compounds were 1,000 fold less active than NA on both oqadrenoceptors from rat aorta and x2-adrenoceptors. The rank order ofpotency ofthe (-)-forms on oqadrenoceptors from rat anococcygeus was NA = m-synephrine > m-octopamine >p-octopamine = p-synephrine. m-Octopamine was 4 fold less active than NA and (-)-m-synephrine. The two pcompounds were 30 fold less active than NA. 3 The rank order of potency of the (+)-forms was NA>m-octopamine>m-synephrine>p-octopamine >p-synephrine on both a,-and M2-adrenoceptors. The potency ofeach ( + )-form was 1-2 orders of magnitude less than that of the (-) counterpart, the differences being greater for the stereoisomers of synephrine than for those of octopamine on both a,-and M2-adrenoceptors. 4 The yohimbine diastereoisomer antagonists, rauwolscine and corynanthine, were tested against (-)-NA and (-)-m-octopamine-induced contractions in both preparations. Based upon the known selectivities of these isomers for a-adrenoceptor subtypes, it is concluded that the rat aorta contains only a,-adrenoceptors while the rabbit saphenous vein possesses predominantly M2-adrenoceptors.5 Ligand binding data for the octopamine and synephrine stereoisomers at oq-and a2-binding sites from rat cerebral cortex was also obtained. (-)-Forms were more active than (+ )-forms. The rank order of affinity of the (-)-forms for both a,-and M2-binding sites was NA > m-octopamine = msynephrine >p-synephrine >p-octopamine. The relative affinities ofthe members ofthe series against a,-binding sites were very similar to their relative functional activities on rat aorta. However, the affinities of both m-and p-compounds relative to that of ( -)-NA were much greater at the x2-binding sites than were the relative activities in rabbit saphenous vein, possibly suggesting low intrinsic efficacy. Functional antagonist responses to NA by the (-)-octopamine and synephrines could not, however, be demonstrated on rat aorta or rabbit saphenous vein. 6 The activities of m-octopamine and m-synephrine were not significantly different from each other on either a,-adrenoceptors from rat aorta or x2-adrenoceptors; however, m-synephrine is more active than m-octopamine on a,-adrenoceptors from rat anococcygeus. Both m-octopamine and msynephrine can be considered to be naturally occurring x,-selective amines. However, if m-and poctopamine are co-released with NA in amounts proportional to their concentration, it is concluded that their activities on m,-and x2-adrenoceptors are too low to be ...

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Section: Methodssupporting

confidence: 78%

Section: Methodsmentioning

confidence: 99%

Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

Brown¹,

McGrath

Midgley

et al. 1988

British J Pharmacology

100

View full text Add to dashboard Cite

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“…Such a role for the vascular endothelium has also been reported in human isolated vessels, particularly human coronary arteries (Thom et al, 1985;Bossaller et al, 1986;Forstermann et al, 1986b). In addition, the presence of endothelium can modulate agonist-induced contractile responses of some animal arteries (Cocks & Angus, 1983;Egleme et al, 1984;Miller et al, 1984;Lues & Schumann, 1984;Godfraind et al, 1985;Carrier & White, 1985;Miller & Vanhoutte, 1985), probably as a consequence of a spontaneous release of ('basal') EDRF (Malta et al, 1986a;Martin et al, 1986). To date, there has been no evidence for basal release of EDRF in human isolated arteries.…”

Section: Introductionmentioning

confidence: 93%

“…It has been shown that agonist-induced contractions of vascular smooth muscle which are relatively resistant to the modulatory effect of the endothelium are also relatively resistant to the effect of calcium entry blockers (Egleme et al, 1984;Godfraind et al, 1985). Therefore it has been proposed that EDRF could affect receptor-operated Ca2 +-gating in vascular smooth muscle (Godfraind, 1986).…”

Section: Contractile Experimentsmentioning

confidence: 99%

Modulatory role of the vascular endothelium in the contractility of human isolated internal mammary artery

Schoeffter

Dion

Godfraind

1988

British J Pharmacology

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1 Endothelium-dependent relaxant responses and modulation of contractile responses were investigated in human isolated 'internal mammary artery (HIMA), a vessel widely used for coronary bypass surgery.2 Acetylcholine and ionophore A23187 (both l0nM-l pM) elicited concentration-dependent relaxations of precontracted HIMA. These relaxations were abolished after rubbing of the endothelium, they were inhibited by methylene blue and were insensitive to indomethacin.3 Histamine at concentrations lower than 10pM elicited an endothelium-dependent, methylene blue-sensitive relaxation of precontracted HIMA. This effect of histamine was inhibited by the Hl-receptor antagonist mepyramine. Bradykinin, noradrenaline and a2-adrenoceptor agonists (in the presence of prazosin) did not relax unrubbed HIMA in which acetylcholine or A23187 were shown to be efficient.4 Tissue levels of guanosine-3':5'-monophosphate (cyclic GMP) were found to be significantly higher in unrubbed HIMA rings than in matched rubbed rings. 5 Methylene blue evoked a slow contraction in resting HIMA, and this contraction was significantly greater in unrubbed than in rubbed preparations. Also, methylene blue enhanced the contractile response of HIMA to noradrenaline and this potentiating effect was significantly greater in unrubbed than in rubbed preparations. Indomethacin induced a slow contraction, of similar magnitude in unrubbed and rubbed HIMA rings.6 In resting HIMA, the concentration-effect curve of noradrenaline-induced contraction was significantly shifted to the left after rubbing of the endothelium, without change in the maximal responses. In unrubbed rings the EC50 value of noradrenaline was about 2 fold that in rubbed rings.7 Histamine also contracted resting HIMA in a concentration-dependent manner and in addition, it triggered rhythmic activity. This rhythmic activity was more prominent in unrubbed preparations and could be partially inhibited by indomethacin. The concentration-effect curve of histamineinduced contractions was displaced to the left after rubbing the endothelium, without changes in the maximal responses. The EC50 value of histamine in unrubbed rings was 4 to 9 fold that found in rubbed rings, depending on the level of tension taken into account for the concentration-effect curve during rhythmic contractions. 8 In the presence of nifedipine (3 pM), noradrenaline-induced contractions were not significantly altered, whereas histamine-induced contractions were found to be inhibited by about 70%. 9 It is concluded that in HIMA, both spontaneous and stimulated endothelium-dependent relaxing factor (EDRF) release may occur, and that basal EDRF can itself be responsible for the modulatory effect of endothelium on contractile responses.

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“…However, the mechanisms by which cyclic GMP produce relaxation of vascular smooth muscle remain to be defined. The effect of cyclic GMP on smooth muscle calcium homeostasis such as plasma membrane Ca ++ influx, sarcoplasmic reticulum Ca ++ release, and plasma membrane Ca ++ extrusion have been studied [148][149][150][151]. The role of potassium channels in hyperpolarization induced by nitrates and by acetylcholine has been investigated [152,153].…”

Section: Vasorelaxant Properties Of Peroxyni-tritementioning

confidence: 99%

Potential Benefits of Peroxynitrite

Nossaman

Kadowitz²

2008

TOPHARMJ

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Peroxynitrite (PN) is generated by the reaction of nitric oxide (NO) and superoxide in one of the most rapid reactions in biology. Studies have reported that PN is a cytotoxic molecule that contributes to vascular injury in a number of disease states. However, it has become apparent that PN has beneficial effects including vasodilation, inhibition of platelet aggregation, inhibition of inflammatory cell adhesion, and protection against ischemia/reperfusion injury in the heart. It is our hypothesis that PN may serve to inactivate superoxide and prolong the actions of NO in the circulation. This manuscript reviews the beneficial effects of PN in the cardiovascular system. Keywords:Nitric oxide/*metabolism, nitric oxide synthase/metabolism/physiology, peroxynitrous acid/metabolism, reactive nitrogen species/metabolism, reactive oxygen species/metabolism, endothelium, vascular/drug effects/metabolism, muscle, smooth, vascular/drug effects/*metabolism, vasodilator agents/adverse effects, oxidative stress/*physiology, vasodilation/drug effects.

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Role of endothelium in the contractile response of rat aorta to α-adrenoceptor agonists

Cited by 108 publications

References 0 publications

Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

Modulatory role of the vascular endothelium in the contractility of human isolated internal mammary artery

Potential Benefits of Peroxynitrite

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