Vascular effects of adenosine and its analogues

Prentice, D.J.

doi:10.1002/ddr.1133

Cited by 3 publications

(8 citation statements)

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“…1 and 2). These results are in complete agreement with those reported by Prentice et al [12,13], and, as a whole, they suggest that vasodilator effects produced by adenosine analogues in aortic rings isolated of several species, are not mediated by any of the adenosine receptors at present identified. It is reasonable to assume that such effects might be mediated by an unknown receptor activated by R-PIA and other adenosine analogues.…”

Section: Discussionsupporting

confidence: 83%

“…The vasodilator effects of adenosine in coronary vessels are mediated by A 2A receptors [5,6], while adenosine-induced aortic relaxation in mice is produced through the activation of A 2B receptor subtype [5]. However, a number of experiments using aortic rings isolated from different animal species have shown that relaxant effects evoked by adenosine analogues are resistant to adenosine receptor antagonists [7][8][9][10][11], suggesting that such effects are not mediated by any of the adenosine receptors at present identified [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Evidence for a Role of Cyclic AMP and Endothelium in Rat Aortic Relaxation Induced by R-PIA

Allende

Acevedo²

2011

TOCVJ

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It is known that vasodilator effects of adenosine are mediated by A 2 receptors in various animal species. Nevertheless, in several blood vessels there is evidence for vasodilator responses to some adenosine analogues, which are resistant to the antagonists of the different adenosine receptor subtypes, suggesting that they are not mediated by any of the known adenosine receptors. There are contradictory reports about the effects produced by adenosine and its analogues on aortic vasodilation. The results obtained in the present study dealing with rat aortic rings and the relaxant effects induced by the selective adenosine A 1 receptor agonist N 6 -R-phenylisopropyladenosine (R-PIA) provide evidence that cyclic AMP and the presence of endothelium are possibly involved in rat aortic relaxation induced by this adenosine analogue.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Evidence for a Role of Cyclic AMP and Endothelium in Rat Aortic Relaxation Induced by R-PIA

Allende

Acevedo²

2011

TOCVJ

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“…Such responses have been described in the guinea-pig, rat and hamster aorta and the rat mesenteric artery (Collis and Brown 1983;Lewis et al 1994;Prentice andHourani 1996, 2000;, as well as in some non-vascular tissues such as the guinea-pig trachea (Brackett and Daly 1991) and taenia caeci . The mechanism for this relaxation is unknown, but it is independent of the presence of endothelium or the production of nitric oxide (Lewis et al 1994;Prentice andHourani 1996, 2000;. In the rat aorta we have recently shown that it does not involve either adenylate or guanylate cyclase, in contrast to relaxations mediated by the A 2A receptors which involve both cyclic AMP and cyclic GMP .…”

Section: Introductionmentioning

confidence: 93%

“…The vasodilator effects of adenosine are in general mediated by receptors of the A 2A or A 2B subtype, while A 1 receptors cause constriction of certain blood vessels and the role, if any, of A 3 receptors in blood vessels is unclear (see Ralevic and Burnstock 1998). In addition to these receptor-mediated effects, however, relaxant responses to adenosine and some of its analogues in some blood vessels have been found to be resistant to adenosine receptor antagonists (see Prentice 2001 for review). Such responses have been described in the guinea-pig, rat and hamster aorta and the rat mesenteric artery (Collis and Brown 1983;Lewis et al 1994;Prentice andHourani 1996, 2000;, as well as in some non-vascular tissues such as the guinea-pig trachea (Brackett and Daly 1991) and taenia caeci .…”

Section: Introductionmentioning

confidence: 98%

“…In addition to these receptor-mediated effects, however, relaxant responses to adenosine and some of its analogues in some blood vessels have been found to be resistant to adenosine receptor antagonists (see Prentice 2001 for review). Such responses have been described in the guinea-pig, rat and hamster aorta and the rat mesenteric artery (Collis and Brown 1983;Lewis et al 1994;Prentice andHourani 1996, 2000;, as well as in some non-vascular tissues such as the guinea-pig trachea (Brackett and Daly 1991) and taenia caeci . The mechanism for this relaxation is unknown, but it is independent of the presence of endothelium or the production of nitric oxide (Lewis et al 1994;Prentice andHourani 1996, 2000;.…”

Section: Introductionmentioning

confidence: 98%

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Relaxation of the mouse isolated aorta and carotid artery in response to adenosine analogues in genetically-modified mice lacking the adenosine A 2A receptor

Prentice

Kelly

Ledent

et al. 2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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The aim of this study was to characterise the receptor(s) mediating responses to adenosine and/or adenosine analogues in mouse isolated aorta and carotid artery. In addition, since mice lacking the A(2A) adenosine receptor are reported to be hypertensive, the possibility that this gene deletion or the altered phenotype results in alteration of responses mediated via adenosine analogues was investigated. This was achieved by comparing results obtained in parallel within single experiments using tissues from A(2A) knock-out animals and their wild-type littermates.In aortic rings, adenosine and 5'- N-ethylcarboxamidoadenosine (NECA) caused relaxations above 10 microM and 30 microM, respectively, which were unaffected by either 8-sulphophenyltheophylline (8-SPT, 100 microM) or A(2A) receptor knockout. 2-[ p-(2-Carbonylethyl)phenylethylamino]-5'- N-ethylcarboxamidoadenosine (CGS 21680) was virtually inactive. R- N(6)-Phenylisopropyladenosine (R-PIA) induced relaxations which were not inhibited by 8-SPT (100 microM) or altered by A(2A) receptor knockout. No A(1)-mediated contractile responses were observed in wild-type or knock-out tissues in contrast with results in mice of the same strain obtained commercially rather than from our breeding programme. In carotid artery rings NECA contracted at low concentrations (0.1-1 microM) and relaxed at higher concentrations. Curves to NECA were not different in tissues from wild-type and A(2A) receptor knock-out mice and both the contractile and relaxant phases were right-shifted by 8-SPT (100 microM) in tissues from animals of both genotype. 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX, 3 nM) attenuated contractile NECA responses but did not affect relaxant responses. CGS 21680 was inactive in carotid artery rings from both wild-type and A(2A) receptor knock-out mice. In the presence of DPCPX (30 nM) to abolish contractions, R-PIA induced relaxant curves which were not different in tissues from wild-type and A(2A) knock-out mice and were not inhibited by 8-SPT (100 microM). These results confirm the absence of A(2A) or A(2B) receptors in murine aorta and suggest that relaxations to NECA in carotid artery are A(2B) receptor-mediated whilst contractions are A(1) receptor-mediated. They also indicate the presence of an antagonist-resistant site activated by R-PIA in both vascular preparations. There is no evidence for compensatory changes in responses mediated by adenosine and its analogues due to the gene deletion or the reported resulting hypertensive phenotype in either aortic or carotid arterial rings obtained from A(2A) knock-out mice.

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Role of cyclic nucleotides in vasodilations of the rat thoracic aorta induced by adenosine analogues

Hourani

Boon

Fooks

et al. 2001

British J Pharmacology

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1 Although adenosine analogues such as 5'-N-ethylcarboxamidoadenosine (NECA) relax the rat thoracic aorta in a partially endothelium-dependent manner via adenosine A 2A receptors, others such as N 6 -R-phenylisopropyladenosine (R-PIA) act via an endothelium-independent, antagonistinsensitive mechanism. The role of cyclic nucleotides in these relaxations was investigated in isolated aortic rings using inhibitors of adenylate and guanylate cyclases as well as subtype-selective phosphodiesterase inhibitors. 2 The adenylate cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536; 100 mM) signi®cantly inhibited responses to NECA, but not responses to R-PIA. The type IV (cyclic AMPselective) phosphodiesterase inhibitor 4-[(3-butoxy-4-methoxyphenyl)methyl]-2-imidazolidinone (RO 20-1724; 30 mM) signi®cantly enhanced responses to NECA and to a lesser extent those to R-PIA. 3 The guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo [4,3a]quinoxalin-1-one (ODQ; 100 mM) signi®cantly inhibited responses to NECA and acetylcholine but not responses to R-PIA. The selective phosphodiesterase V (cyclic GMP-selective) inhibitors, zaprinast (10 mM) and 4-{[3',4'-(methylenedioxy)benzyl]amino}-6-methoxyquinazoline (MMQ; 1 mM), had no signi®cant e ect on responses to either NECA or R-PIA, but enhanced responses to acetylcholine. 4 These results are consistent with the e ects of NECA being via activation of endothelial receptors to release NO which stimulates guanylate cyclase, as well as smooth muscle receptors coupled to stimulation of adenylate cyclase. The lack of e ect of zaprinast and MMQ on responses to NECA are likely to be due to simultaneous activation of both adenylate and guanylate cyclases in the smooth muscle, as cyclic AMP reduces the sensitivity of phosphodiesterase V to inhibitors. These results also suggest that the e ects of R-PIA are via neither of these mechanisms.

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Vascular effects of adenosine and its analogues

Cited by 3 publications

References 24 publications

Evidence for a Role of Cyclic AMP and Endothelium in Rat Aortic Relaxation Induced by R-PIA

Evidence for a Role of Cyclic AMP and Endothelium in Rat Aortic Relaxation Induced by R-PIA

Relaxation of the mouse isolated aorta and carotid artery in response to adenosine analogues in genetically-modified mice lacking the adenosine A 2A receptor

Role of cyclic nucleotides in vasodilations of the rat thoracic aorta induced by adenosine analogues

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