Role of cyclic GMP in the modulation by endothelium of the adrenolytic action of prazosin in the rat isolated aorta

Alosachie, Iyad; Godfraind, Théophile

doi:10.1111/j.1476-5381.1986.tb11152.x

Cited by 34 publications

(15 citation statements)

References 29 publications

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“…It is known that, in certain blood vessels, removal of endothelium can potentiate the responses of vascular smooth muscle to AVP (Katusic & Krstic, 1987;Randall et al, 1988). In addition, it has been shown in numerous blood vessels that the endothelium-dependent modulation of agonistinduced contractile responses is related to release of relaxing factors from the endothelium, which in turn result in a reduction of agonist potency and efficacy (Alosachie & Godfraind, 1986;Pipili-Synetos et al, 1991;Adeagbo & Triggle, 1993). However, in the present study removal of the endothelium did not affect the response to AVP.…”

Section: Discussionmentioning

confidence: 99%

Characterization of arginine vasopressin actions in human uterine artery: lack of role of the vascular endothelium

Jovanović

Grbović

Žikić

et al. 1995

British J Pharmacology

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Section: Discussionmentioning

confidence: 99%

Characterization of arginine vasopressin actions in human uterine artery: lack of role of the vascular endothelium

Jovanović

Grbović

Žikić

et al. 1995

British J Pharmacology

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“…Recently we have reported that in rat isolated aorta, the modulation by endothelium of agonistinduced contractile response is related to an increase of cyclic GMP levels in vascular smooth muscles evoked by the release of EDRF, which in turn could result in a reduction of agonist efficacy and receptor reserve (Alosachie & Godfraind, 1986). This suggestion is in agreement with Malta et al (1986) and Martin et al (1986) who have also proposed a similar relation between endothelium modulation of agonist-induced contractile response and a possible I The Macmillan Press Ltd 1988 alteration of agonist efficacy by EDRF.…”

Section: Introductionmentioning

confidence: 99%

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

Alosachie

Godfraind

1988

British J Pharmacology

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1 We have examined the effect of endothelium on the antagonistic action of prazosin, doxazosin, yohimbine and phentolamine against phenylephrine, clonidine and noradrenaline. 2 The action of prazosin against phenylephrine was similar to that earlier reported against noradrenaline, acting as a non-competitive antagonist in the presence of endothelium and as a competitive antagonist in the absence of endothelium. Prazosin also acted as a non-competitive antagonist against clonidine in the absence of endothelium. 3 Doxazosin behaved in a similar way to prazosin against noradrenaline, phenylephrine and clonidine acting as a non-competitive antagonist in the presence of endothelium and as competitive antagonist after removal of endothelium. In contrast, yohimbine and phentolamine acted as competitive antagonists both in the presence and in the absence of endothelium. 4 Analysis of the concentration-response curves for noradrenaline, phenylephrine and clonidine in the presence and in the absence of endothelium showed that the affinity for all three agonists was the same but not the efficacy and the receptor reserve, both of which were lower in the presence than in the absence of endothelium. 5The rank order of agonist potency in the absence of endothelium was noradrenaline > phenylephrine > clonidine. The rank order of antagonist potency was prazosin > doxazosin > phentolamine > yohimbine. 6 The results show that vascular endothelium modulates the contractile response to a-adrenoceptor agonists and also modifies the action of the antagonists prazosin and doxazosin but not that of yohimbine and phentolamine. This effect of endothelium was related to a change in agonist efficacy and receptor reserve. These results also suggest that the a-adrenoceptors of the isolated aorta of the rat are predominantly, if not exclusively of the a1-subtype.

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“…In order to compare the contribution of different a-adrenoceptor subtypes to the noradrenaline-induced contraction between vessels studied, we used prazosin, a predominantly mladrenoceptor antagonist (Cambridge et al, 1977;Starke, 1981;Skarby & Larsson, 1987) and yohimbine, a predominantly M2-adrenoceptor antagonist (Doxey et al, 1977;Ruffolo et al, 1981;Goldberg & Robertson, 1983). Although both antagonists are considered as competitive, Alosachie & Godfraind (1986 (Arunlakshana & Schild, 1959). It is known that the KB value for a specific antagonist acting on the same type of receptor in different preparations should be the same (Furchgott, 1972).…”

Section: Discussionmentioning

confidence: 99%

Effect of the vascular endothelium on noradrenaline‐induced contractions in non‐pregnant and pregnant guinea‐pig uterine arteries

Jovanović¹,

Grbović²,

Jovanović

1995

British J Pharmacology

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1 The effect of pregnancy on noradrenaline-mediated contraction of guinea-pig uterine artery rings with both intact and denuded endothelium was investigated.2 Noradrenaline (25 nM -I00 #Lm) induced concentration-dependent contraction of non-pregnant and pregnant guinea-pig uterine arterial rings with intact endothelium with similar pD2 and maximal response values (non-pregnant: pD2= 5.85 ± 0.02, maximal response = 121 ± 8.2%; pregnant: pD2 = 5.81 ± 0.04, maximal response = 122 + 9.1%). Removal of endothelium did not affect noradrenaline-induced contractions in non-pregnant guinea-pig uterine artery (pD2= 5.97 ± 0.02, maximal response = 119 ± 8.6%). In contrast, in arteries from pregnant guinea-pigs, removal of endothelium shifted concentration-response curve for noradrenaline to the left, without affecting maximal response value (pD2 = 6.36 ± 0.03, maximal response = 120 ± 9.0%).3 The pKA values for noradrenaline were: 5.76 ± 0.09 and 5.82 ±0.10 for non-pregnant guinea-pig uterine artery with intact and denuded endothelium, respectively and 5.74 ± 0.09 and 5.72 ± 0.07 for pregnant guinea-pig uterine artery with intact and denuded endothelium, respectively. 4 The receptor occupancy-response relationship for noradrenaline was linear for all types of vessels, except for pregnant guinea-pig uterine artery with denuded endothelium, since half-maximal response to noradrenaline was obtained with 44.8 ± 6.9% (non-pregnant guinea-pig uterine artery with intact endothelium), 43.3 ± 6.1% (non-pregnant guinea-pig uterine artery with denuded endothelium) and 44.3 ± 6.3% (pregnant guinea-pig uterine artery with intact endothelium) receptor occupancy. In pregnant guinea-pig uterine artery with denuded endothelium, occupancy-response relationship for noradrenaline was non-linear since half-maximal response to noradrenaline was obtained with 19.7 ± 3.3% receptor occupancy.5 N0-monomethyl-L-arginine(100gM) and indomethacin (10 gM) did not affect concentration-response curve for noradrenaline in guinea-pig uterine arteries, regardless of pregnancy status or endothelial condition.6 In quiescent preparations, the z-adrenoceptor antagonists, prazosin (5-50nM) and yohimbine (1-10gM) produced parallel rightward shifts of the curves for noradrenaline and the slopes of the Schild plots were not significantly different from unity. The plots constrained to a slope of unity gave the following -log KB values: prazosin vs. yohimbine 8.78 ± 0.03 vs. 6.41 ± 0.02 for non-pregnant guineapig uterine artery with intact endothelium, 8.95 ± 0.03 vs. 6.34 ± 0.02 for non-pregnant guinea-pig uterine artery with denuded endothelium, 8.91 ± 0.01 vs. 6.44 ± 0.03 for pregnant guinea-pig uterine artery with intact endothelium and 9.07 ± 0.01 vs. 6.52 ± 0.03 for pregnant guinea-pig uterine artery with denuded endothelium.7 It is concluded that initially there is no difference in noradrenaline action between uterine arteries from non-pregnant and pregnant guinea-pigs, but after removal of the endothelium the pregnant guinea-pig uterine artery is more sensitive...

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Role of cyclic GMP in the modulation by endothelium of the adrenolytic action of prazosin in the rat isolated aorta

Cited by 34 publications

References 29 publications

Characterization of arginine vasopressin actions in human uterine artery: lack of role of the vascular endothelium

Characterization of arginine vasopressin actions in human uterine artery: lack of role of the vascular endothelium

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

Effect of the vascular endothelium on noradrenaline‐induced contractions in non‐pregnant and pregnant guinea‐pig uterine arteries

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