Relaxant effects of ATP and adenosine on canine large and small coronary arteries in vitro

doi:10.1016/0014-2999(87)90741-2

European Journal of Pharmacology

Volume 143, Issue 1, 3 November 1987, Pages 119-126

https://doi.org/10.1016/0014-2999(87)90741-2 Get rights and content

Abstract

Rings from greyhound large (3–4 mm internal diameter) and small (less than 200 μ m internal diameter) coronary arteries were mounted in water-jacketed tissue baths or a Mulvany myograph, respectively. Relaxations to ATP and adenosine were determined in arteries precontracted with the thromboxane A₂ mimetic U46619 or with K⁺, ATP was a much more effective relaxant of large arteries than adenosine. ATP relaxed large coronaries by an endothelium-dependent mechanism whereas relaxations to adenosine were not endothelium-dependent. In contrast, adenosine appeared to be slightly more effective than ATP in relaxing small coronary arteries. Moreover, adenosine was more effective in relaxing K⁺-contracted small coronaries than K⁺-contracted large coronary arteries. These results suggest that ATP may be a more significant relaxant of large coronaries than adenosine but that adenosine may be a more significant relaxant than ATP in small coronary arteries.

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Cited by (54)

Cellular distribution and functions of P2 receptor subtypes in different systems
2004, International Review of Cytology
Citation Excerpt :
ATP and ADP induced vasodilatation of isolated canine, guinea pig, and rabbit coronary arteries (Keef et al., 1992; Toda et al., 1982) and the coronary vasculature of the guinea pig and rat heart via an action on P2Y receptors on the endothelium (Hopwood and Burnstock, 1987; Nees, 1989). Vasodilatation in response to ATP induced the formation of NO in the guinea pig and dog heart (Houston et al., 1987; Keef et al., 1992; Lee et al., 1990; White and Angus, 1987). Since UTP and 2-MeSATP both induce vasodilatation of the guinea pig coronary vasculature (Vials and Burnstock, 1993) the presence of two separate P2 receptors is indicated.
This review is aimed at providing readers with a comprehensive reference article about the distribution and function of P2 receptors in all the organs, tissues, and cells in the body. Each section provides an account of the early history of purinergic signaling in the organ⧸cell up to 1994, then summarizes subsequent evidence for the presence of P2X and P2Y receptor subtype mRNA and proteins as well as functional data, all fully referenced. A section is included describing the plasticity of expression of P2 receptors during development and aging as well as in various pathophysiological conditions. Finally, there is some discussion of possible future developments in the purinergic signaling field.
Pharmacology of adenosine receptors in the vasculature
2001, Pharmacology and Therapeutics
Adenosine is widely distributed in mammals. One of the primary roles of adenosine within the cardiovascular system is to directly control the functions of both cardiac and vascular tissues. Recently, there has been considerable interest in the subclassification of adenosine receptors. Characterization of a heterogeneous population of receptors for adenosine could provide an opportunity for the development of novel compounds of therapeutic value. Adenosine is released from cells as a result of metabolism, and its release can be increased dramatically from cells that are metabolically stressed. This implies that adenosine can be released from a variety of cells throughout the body, as a result of increased metabolic rates, in concentrations that can have a profound impact on blood vessel function and, consequently, blood flow. It is recognized that the actions of this nucleoside on the vasculature are most prominent when oxygen demand is high and there is a reduction in oxygen tension at the site in question. Therefore, it is not surprising that adenosine has been shown to be an important regulator of blood vessel tone under hypoxic conditions. Furthermore, the activation of adenosine receptors on blood vessels can result in relaxation and/or contractions. The nature of the response subsequent to the activation of adenosine receptors is primarily dependent on the type of blood vessel involved and basal tone. This review will focus on the characterization of subtypes of adenosine receptors in blood vessels, as well as the effect of the stimulation of adenosine receptors on the peripheral circulation.
Increase in the vasorelaxant potency of K(ATP) channel opening drugs by adenosine A<inf>1</inf> and A<inf>2</inf> receptors in the pig coronary artery
1999, European Journal of Pharmacology
Myograph recording from ring segments of pig small coronary arteries was used to investigate the effects of adenosine receptor activation on the vasorelaxant potency of ATP-sensitive K⁺ channel opening drugs. Receptor activation with 2-chloroadenosine (2-CA, 300 nM) increased the potency of both nicorandil and levcromakalim, shifting the pEC₅₀s from 4.68±0.03 to 5.05±0.04 and from 6.34±0.06 to 6.72±0.06, respectively (P<0.05 in each case). Experiments with selective adenosine receptor agonists (2-chloro-N⁶-cyclopentyladenosine (CCPA), 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680)) and antagonists (8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a] [1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385)) suggest that both A₁ and A_2a receptors can increase the potency of nicorandil, while that of levcromakalim is increased only by A₂ receptors. Adenosine receptor activation did not affect the potency of pinacidil. Thus, adenosine receptor activation can increase the potency of some K⁺ channel opening drugs to relax coronary arteries, but the details of the interaction with adenosine receptors depend on the particular drug.
Age-related changes in adenosine in rat coronary resistance vessels
1999, General Pharmacology
- 1.
  The vasodilator effects of adenosine receptor agonists, isoprenaline and histamine were examined in perfused heart preparations from young (4–6 weeks) and mature (12–20 weeks) rats.
- 2.
  Adenosine induced a biphasic concentration-dependent decrease in KCl (35 mM) raised coronary perfusion pressure in hearts from young and mature rats, suggesting the presence of both high- and low-affinity sites for adenosine receptors in the two age groups tested. In heart preparations from mature rats, vasodilator responses to adenosine were significantly reduced compared with responses observed in young rats.
- 3.
  Responses to 5′-N-ethylcarboxamidoadenosine (NECA) and 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680) were reduced in preparations from mature rats, whereas the vasodilator actions of N⁶-cyclopentyladenosine (CPA) and N⁶-2-(4-aminophenyl)ethyladenosine (APNEA) did not change with age.
- 4.
  The results presented in this study suggest that several adenosine receptor subtypes mediate vasodilator responses in the coronary circulation of the rat and that a reduction in response to adenosine with age may be due to changes in the high-affinity receptor site.
Nucleotide-evoked relaxation of human coronary artery
1998, European Journal of Pharmacology
Endothelium-dependent dilation of coronary blood vessels in response to ATP and related nucleotides has been demonstrated in various animal species. The aim of the present study was to investigate a possible relaxant effect of ATP, the adenine nucleotides 2-methylthio ATP (MeSATP) and adenosine 5′-O-(2-thiodiphosphate) (ADPβS), and the pyrimidine nucleotide UTP in isolated human coronary artery. In endothelium-intact rings of human coronary artery precontracted with K⁺ (20–40 mM), the nucleotides caused relaxation. Average maximal percentage relaxations and average EC₅₀ values (concentrations causing half-maximal relaxation) were 89% and 47.1 μM for ATP, 28% and 0.3 μM for MeSATP, 35% and 0.6 μM for ADPβS, and 49% and 1.6 μM for UTP. For each of the four agonists, the potency to elicit relaxation varied greatly between individual rings, so that equi-relaxing concentrations spanned several orders of magnitude. Moreover, the sensitivities to ATP and UTP, when tested in the same ring, were not correlated. Mechanical removal of the endothelium as well as N^G-nitro-l-arginine methyl ester (l-NAME; 30 μM), an inhibitor of nitric oxide synthase, abolished the relaxation caused by MeSATP, ADPβS and UTP and greatly attenuated the response to lower concentrations of ATP (3.2–320 μM), but high concentrations of ATP (320 and 1000 μM) caused relaxation also in endothelium-denuded preparations and in the presence of l-NAME. High concentrations of ADPβS (32 and 100 μM) and UTP (320 and 1000 μM) caused contraction of endothelium-denuded preparations. Thus, extracellular nucleotides cause endothelium-dependent, primarily nitric oxide-mediated relaxation of human coronary artery. ATP in addition causes endothelium-independent relaxation. The receptors activated by the nucleotides appear to be unevenly distributed on the coronary endothelium.
Pharmacological Analysis of responses to ATP in the isolated and perfused canine coronary artery
1997, European Journal of Pharmacology
Vascular responses of the isolated and perfused canine coronary artery to adenosine 5′-triphosphate (ATP) were analyzed pharmacologically. At basal perfusion pressure, ATP induced a vasoconstriction followed by a vasodilation dose-dependently. The potency order for vasoconstriction was α,β-methylene ATP>2-methylthio ATP>UTP>ATP. That for vasodilation was ATP>2-methylthio ATP>α,β-methylene ATP≫UTP in the preparations precontracted by 20 mM KCl. Aminophylline inhibited the vasodilation induced by adenosine, but not that induced by ATP. α,β-Methylene ATP and suramin inhibited the vasoconstriction induced by ATP. Reactive blue 2 inhibited the vasodilation induced by ATP, but not the vasoconstriction. Removal of the endothelium by saponin and l-N^G-nitroarginine inhibited the vasodilation induced by ATP, but indomethacin did not. The results suggest that ATP induces vasoconstriction via P_2X purinoceptors on the smooth muscle and vasodilation via P_2Y purinoceptors on the endothelium through mainly the release of nitric oxide in the canine coronary artery, respectively.

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Relaxant effects of ATP and adenosine on canine large and small coronary arteries in vitro

Abstract

Gen. Pharmacol.

Trends Pharmacol. Sci.

European J. Pharmacol.

European J. Pharmacol.

Criteria for the involvement of adenosine in the regulation of blood flow

Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin

Nature

Release and properties of endothelium-derived relaxing factor (EDRF) from endothelial cells in culture

J. Cell. Physiol.

Role of the intima in cholinergic and purinergic relaxation of isolated canine femoral arteries

J. Physiol. (London)

Kinetics of the thrombin-induced release of adenosine triphosphate by platelets. Comparison with release of calcium

Biochemistry

Release of adenosine triphosphate from isolated heart cells in response to hypoxia

J. Physiol. (London)

Role of the endothelium in responses of vascular smooth muscle

Circ. Res.