Release inhibitory receptors activation favours the A<sub>2A</sub>‐adenosine receptor‐mediated facilitation of noradrenaline release in isolated rat tail artery

Fresco, Paula; Diniz, Carmen; Queiróz, Glória; Gonçalves, Jorge

doi:10.1038/sj.bjp.0704686

Cited by 24 publications

(13 citation statements)

References 33 publications

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“…Electrically evoked tritium overflow from tissue preparations incubated with [ 3 H]-noradrenaline has been shown to reflect action potential-evoked neuronal NA release (20) and the drug-induced changes in evoked tritium overflow may be assumed to reflect changes in neuronal NA release, as observed in previous studies (3,4).…”

Section: Na Release From Sympathetic Nerve Terminalsmentioning

confidence: 79%

Impaired Inhibitory Function of Presynaptic A1-Adenosine Receptors in SHR Mesenteric Arteries

et al. 2013

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Abstract. In hypertension, vascular reactivity alterations have been attributed to numerous factors, including higher sympathetic innervation/adenosine. This study examined the modulation of adenosine receptors on vascular sympathetic nerves and their putative contribution to higher noradrenaline spillover in hypertension. We assessed adenosine receptors distribution in the adventitia through confocal microscopy, histomorphometry, and their regulatory function on electrically-evoked [3 H]-noradrenaline overflow, using selective agonists/antagonists. We found that: i) A 1 -adenosine receptor agonist (CPA: 100 nM) inhibited tritium overflow to a lower extent in SHR (25% ± 3%, n = 14) compared to WKY (38% ± 3%, n = 14) mesenteric arteries; ii) A 2A -adenosine receptor agonist (CGS 21680: 100 nM) induced a slight increase of tritium overflow that was similar in SHR (22% ± 8%, n = 8) and WKY (24% ± 5%, n = 8) mesenteric arteries; iii) A 2B -and A 3 -adenosine receptors did not alter tritium overflow in either strain; iv) all adenosine receptors were present on mesenteric artery sympathetic nerves and/or some adventitial cells of both strains; and v) A 1 -adenosine receptor staining fractional area was lower in SHR than in WKY mesenteric arteries. We conclude that there is an impaired inhibitory function of vascular presynaptic A 1 -adenosine receptors in SHR, likely related to a reduced presence of these receptors on sympathetic innervation, which might lead to higher levels of noradrenaline in the synaptic cleft and contribute to hypertension in this strain.

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Section: Na Release From Sympathetic Nerve Terminalsmentioning

confidence: 79%

Impaired Inhibitory Function of Presynaptic A1-Adenosine Receptors in SHR Mesenteric Arteries

et al. 2013

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“…Postjunctional factors are not an issue with amperometric measures of NE release. In addition, enhancement of NE release by endogenously released adenosine could be attributable to an action at facilitatory A 2A receptors on sympathetic nerve terminals (Fresco et al, 2002;Diniz et al, 2004). Previous work has shown that prejunctional A 2A Rs couple to increased or decreased NE release from perivascular sympathetic nerves (Diniz et al, 2004).…”

Section: Tablementioning

confidence: 99%

Impaired Function of Prejunctional Adenosine A1 Receptors Expressed by Perivascular Sympathetic Nerves in DOCA-Salt Hypertensive Rats

Sangsiri

Dong

Swain

et al. 2013

The Journal of Pharmacology and Experimental Therapeutics

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Increased sympathetic nervous system activity contributes to deoxycorticosterone acetate (DOCA)-salt hypertension in rats. ATP and norepinephrine (NE) are coreleased from perivascular sympathetic nerves. NE acts at prejunctional a 2 -adrenergic receptors (a 2 ARs) to inhibit NE release, and a 2 AR function is impaired in DOCA-salt rats. Adenosine, an enzymatic ATP degradation product, acts at prejunctional A 1 adenosine receptors (A 1 Rs) to inhibit NE release. We tested the hypothesis that prejunctional A 1 R function is impaired in sympathetic nerves supplying mesenteric arteries (MAs) and veins (MVs) of DOCAsalt rats. Electrically evoked NE release and constrictions of blood vessels were studied in vitro with use of amperometry to measure NE oxidation currents and video microscopy, respectively. Immunohistochemical methods were used to localize tyrosine hydroxylase (TH) and A 1 Rs in perivascular sympathetic nerves. TH and A 1 Rs colocalized to perivascular sympathetic nerves. Adenosine and N 6 -cyclopentyl-adenosine (CPA, A 1 R agonist) constricted MVs but not MAs. Adenosine and CPA (0.001-10 mM) inhibited neurogenic constrictions and NE release in MAs and MVs. DOCA-salt arteries were resistant to adenosine and CPA-mediated inhibition of NE release and constriction. The A 2A adenosine receptor agonist CGS21680 (C 23 H 29 N 7 O 6 .HCl.xH 2 O) (0.001-0.1 mM) did not alter NE oxidation currents. We conclude that there are prejunctional A 1 Rs in arteries and both pre-and postjunctional A 1 Rs in veins; thus, adenosine selectively constricts the veins. Prejunctional A 1 R function is impaired in arteries, but not veins, from DOCA-salt rats. Sympathetic autoreceptor dysfunction is not specific to a 2 ARs, but there is a more general disruption of prejunctional mechanisms controlling sympathetic neurotransmitter release in DOCA-salt hypertension.

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“…In fact, it is a high-affinity agonist for both A 1 and A 2A adenosine receptors (Zannikos et al, 2001). Because activation of A 2A receptors can lead to sympatho-excitation (Fresco et al, 2002), including release of NE, lipolysis would be increased, and hence, counteract the antilipolytic effect mediated by A 1 receptor activation. Whether the increase in sympathetic drive can fully explain the apparent rapid loss of A 1 receptor-mediated antilipolytic effect remains to be determined.…”

Section: Antilipolytic Effect Of Cvt-510 Without Bradycardia 229mentioning

confidence: 99%

N-[3-(R)-Tetrahydrofuranyl]-6-aminopurine Riboside, an A₁Adenosine Receptor Agonist, Antagonizes Catecholamine-Induced Lipolysis without Cardiovascular Effects in Awake Rats

Fraser

Gao²,

Ozeck³

et al. 2003

J Pharmacol Exp Ther

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Elevated serum nonesterified free fatty acid (NEFA) concentrations are detrimental to both the mechanical and electrical function of the heart. A 1 adenosine receptor agonists are potent and efficacious inhibitors of lipolysis; however, their cardiovascular effects have limited their use to lower serum NEFA. Our objective was to determine whether the antilipolytic effect of N- [3-(R)-tetrahydrofuranyl]-6-aminopurine riboside (CVT-510), an A 1 agonist, could be distinguished from its bradycardia effect and demonstrated in rats with normal or elevated serum NEFA. Rats were instrumented with telemetry transmitters for continuous recording of heart rate, and catheterized, for delivery of drugs and blood sampling. CVT-510 caused a rapid and sustained dose-dependent decrease in NEFA at doses that did not cause bradycardia (2, 5, and 20 g/kg). Significant bradycardia was observed at 50 g/kg. Norepinephrine (NE) increased NEFA from 0.5 Ϯ 0.01 to 0.9 Ϯ 0.2 mM and this effect lasted for 2 h. CVT-510 (10 g/kg) given at 40 min postinjection of NE reversed the rise in NEFA (69% reduction). When CVT-510 (20 g/kg) was given 15 min before a 30-min long infusion of NE, the lipolytic response to NE was prevented. To mimic the antilipolytic effect of CVT-510 in awake rats, hearts were perfused with palmitate at concentrations similar to those observed in the in vivo studies (0.8 and 0.2 mM), which decreased myocardial oxygen consumption (MVO 2 ) by 11%. Thus, CVT-510 at doses Ն5-fold lower than those that slow heart rate caused a marked and sustained lowering of normal or elevated NEFA, that when mimicked in vitro decreased MVO 2 and would be expected to improve cardiac efficiency.

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Release inhibitory receptors activation favours the A_2A‐adenosine receptor‐mediated facilitation of noradrenaline release in isolated rat tail artery

Cited by 24 publications

References 33 publications

Impaired Inhibitory Function of Presynaptic A1-Adenosine Receptors in SHR Mesenteric Arteries

Impaired Inhibitory Function of Presynaptic A1-Adenosine Receptors in SHR Mesenteric Arteries

Impaired Function of Prejunctional Adenosine A1 Receptors Expressed by Perivascular Sympathetic Nerves in DOCA-Salt Hypertensive Rats

N-[3-(R)-Tetrahydrofuranyl]-6-aminopurine Riboside, an A₁Adenosine Receptor Agonist, Antagonizes Catecholamine-Induced Lipolysis without Cardiovascular Effects in Awake Rats

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Release inhibitory receptors activation favours the A2A‐adenosine receptor‐mediated facilitation of noradrenaline release in isolated rat tail artery

Cited by 24 publications

References 33 publications

Impaired Inhibitory Function of Presynaptic A1-Adenosine Receptors in SHR Mesenteric Arteries

Impaired Inhibitory Function of Presynaptic A1-Adenosine Receptors in SHR Mesenteric Arteries

Impaired Function of Prejunctional Adenosine A1 Receptors Expressed by Perivascular Sympathetic Nerves in DOCA-Salt Hypertensive Rats

N-[3-(R)-Tetrahydrofuranyl]-6-aminopurine Riboside, an A1Adenosine Receptor Agonist, Antagonizes Catecholamine-Induced Lipolysis without Cardiovascular Effects in Awake Rats

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Release inhibitory receptors activation favours the A_2A‐adenosine receptor‐mediated facilitation of noradrenaline release in isolated rat tail artery

N-[3-(R)-Tetrahydrofuranyl]-6-aminopurine Riboside, an A₁Adenosine Receptor Agonist, Antagonizes Catecholamine-Induced Lipolysis without Cardiovascular Effects in Awake Rats