Role of A1 adenosine receptors in regulation of vascular tone

2005 ◽  
Vol 288 (3) ◽  
pp. H1411-H1416 ◽  
Author(s):  
Huda E. Tawfik ◽  
J. Schnermann ◽  
Peter J. Oldenburg ◽  
S. Jamal Mustafa
Keyword(s):  
Adenosine Receptors ◽  
Vascular Tone ◽  
Receptor Subtypes ◽  
Vascular Relaxation ◽  
Response Curves ◽  
Cgs 21680 ◽  
A1 Adenosine Receptors ◽  
The Impact ◽  
Regulation Of Vascular Tone

The vascular response to adenosine and its analogs is mediated by four adenosine receptors (ARs), namely, A1, A2A, A2B, and A3. A2AARs and/or A2BARs are involved in adenosine-mediated vascular relaxation of coronary and aortic beds. However, the role of A1ARs in the regulation of vascular tone is less well substantiated. The aim of this study was to determine the role of A1ARs in adenosine-mediated regulation of vascular tone. A1AR-knockout [A1AR(−/−)] mice and available pharmacological tools were used to elucidate the function of A1ARs and the impact of these receptors on the regulation of vascular tone. Isolated aortic rings from A1AR(−/−) and wild-type [A1AR(+/+)] mice were precontracted with phenylephrine, and concentration-response curves for adenosine and its analogs, 5′- N-ethyl-carboxamidoadenosine (NECA, nonselective), 2-chloro- N6-cyclopentyladenosine (CCPA, A1AR selective), 2-(2-carboxyethyl)phenethyl amino-5′- N-ethylcarboxamido-adenosine (CGS-21680, A2A selective), and 2-chloro- N6-3-iodobenzyladenosine-5′- N-methyluronamide (Cl-IBMECA, A3 selective) were obtained to determine relaxation. Adenosine and NECA (0.1 μM) caused small contractions of 13.9 ± 3.0 and 16.4 ± 6.4%, respectively, and CCPA at 0.1 and 1.0 μM caused contractions of 30.8 ± 4.3 and 28.1 ± 3.9%, respectively, in A1AR(+/+) rings. NECA- and CCPA-induced contractions were eliminated by 100 nM of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, selective A1AR antagonist). Adenosine, NECA, and CGS-21680 produced an increase in maximal relaxation in A1AR(−/−) compared with A1AR(+/+) rings, whereas Cl-IBMECA did not produce contraction in either A1AR(+/+) or A1AR(−/−) rings. CCPA-induced contraction at 1.0 μM was eliminated by the PLC inhibitor U-73122. These data suggest that activation of A1ARs causes contraction of vascular smooth muscle through PLC pathways and negatively modulates the vascular relaxation mediated by other adenosine receptor subtypes.

scholarly journals The Role of Adenosine A2AReceptor, CYP450s, and PPARs in the Regulation of Vascular Tone

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Maan T. Khayat ◽  
Mohammed A. Nayeem
Keyword(s):  
Vascular Endothelium ◽  
Adenosine Receptors ◽  
Vascular Tone ◽  
Continuous Process ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors ◽  
The Impact

Adenosine is an endogenous mediator involved in a myriad of physiologic functions, including vascular tone regulation. It is also implicated in some pathologic conditions. Four distinct receptor subtypes mediate the effects of adenosine, such as its role in the regulation of the vascular tone. Vascular tone regulation is a complex and continuous process which involves many mechanisms and mediators that are not fully disclosed. The vascular endothelium plays a pivotal role in regulating blood flow to and from all body organs. Also, the vascular endothelium is not merely a physical barrier; it is a complex tissue with numerous functions. Among adenosine receptors,A2Areceptor subtype (A2AAR) stands out as the primary receptor responsible for the vasodilatory effects of adenosine. This review focuses on important effectors of the vascular endothelium, including adenosine, adenosine receptors, EETs (epoxyeicosatrienoic acids), HETEs (hydroxyeicosatetraenoic acids), PPARs (peroxisome proliferator-activated receptors), andKATPchannels. Given the impact of vascular tone regulation in cardiovascular physiology and pathophysiology, better understanding of the mechanisms affecting it could have a significant potential for developing therapeutic agents for cardiovascular diseases.

A novel mechanism of renal blood flow autoregulation and the autoregulatory role of A1 adenosine receptors in mice

2007 ◽  
Vol 293 (5) ◽  
pp. F1489-F1500 ◽  
Author(s):  
Armin Just ◽  
William J. Arendshorst
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Adenosine Receptors ◽  
Time Course ◽  
Tubuloglomerular Feedback ◽  
The Third ◽  
A1 Adenosine Receptors ◽  
The Impact ◽  
Renal Blood Flow Autoregulation

Autoregulation of renal blood flow (RBF) is mediated by a fast myogenic response (MR; ∼5 s), a slower tubuloglomerular feedback (TGF; ∼25 s), and potentially additional mechanisms. A1 adenosine receptors (A1AR) mediate TGF in superficial nephrons and contribute to overall autoregulation, but the impact on the other autoregulatory mechanisms is unknown. We studied dynamic autoregulatory responses of RBF to rapid step increases of renal artery pressure in mice. MR was estimated from autoregulation within the first 5 s, TGF from that at 5–25 s, and a third mechanism from 25–100 s. Genetic deficiency of A1AR (A1AR−/−) reduced autoregulation at 5–25 s by 50%, indicating a residual fourth mechanism resembling TGF kinetics but independent of A1AR. MR and third mechanism were unaltered in A1AR−/−. Autoregulation in A1AR−/− was faster at 5–25 than at 25–100 s suggesting two separate mechanisms. Furosemide in wild-type mice (WT) eliminated the third mechanism and enhanced MR, indicating TGF-MR interaction. In A1AR−/−, furosemide did not further impair autoregulation at 5–25 s, but eliminated the third mechanism and enhanced MR. The resulting time course was the same as during furosemide in WT, indicating that A1AR do not affect autoregulation during furosemide inhibition of TGF. We conclude that at least one novel mechanism complements MR and TGF in RBF autoregulation, that is slower than MR and TGF and sensitive to furosemide, but not mediated by A1AR. A fourth mechanism with kinetics similar to TGF but independent of A1AR and furosemide might also contribute. A1AR mediate classical TGF but not TGF-MR interaction.

Role of endothelins in regulation of vascular tone in the in situ perfused rat adrenals

1998 ◽  
Vol 274 (1) ◽  
pp. E1-E5 ◽  
Author(s):  
Giuseppina Mazzocchi ◽  
Ludwik K. Malendowicz ◽  
Francesco G. Musajo ◽  
Giuseppe Gottardo ◽  
Anna Markowska ◽  
...  
Keyword(s):  
Flow Rate ◽  
Vascular Tone ◽  
Receptor Subtypes ◽  
Left Adrenal Gland ◽  
Kinase C ◽  
Rat Adrenals ◽  
Oxide Synthase ◽  
Regulation Of Vascular Tone

This study examined the role of endothelins (ETs) and their receptor subtypes ETAand ETB in the regulation of vascular tone in the in situ perfused rat left adrenal gland. Endothelin-1 (ET-1), which binds both ETA and ETB receptors, decreased adrenal flow rate of the perfusion medium, and its effect was reversed by the ETA antagonist BQ-123 and enhanced by the ETB antagonist BQ-788. ET-3, which preferentially binds ETB, and the selective ETB agonist BQ-3020 increased adrenal flow rate of perfusate, and their effects were annulled by BQ-788. BQ-123 magnified the effect of ET-3 and did not affect that of BQ-3020. The ETA-mediated decrease and the ETB-mediated rise in the rate of collection of perfusate were abolished by Ro-31–8220, an inhibitor of protein kinase C (PKC), and by N G-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase (NOS), respectively. Collectively, these findings suggest that ETs can regulate vascular tone in the in situ perfused rat adrenals via both PKC-coupled ETA and NOS-coupled ETB receptors, the activation of which evokes vasoconstriction and vasodilation, respectively.

Role of Adenosine Receptors in Rare Neurodegenerative Diseases with Motor Symptoms

2021 ◽  
Vol 22 ◽  
Author(s):  
Vicent Beltran-Beltran ◽  
Noelia Benetó ◽  
Tamara Lapeña-Luzón ◽  
Laura R. Rodríguez ◽  
Federico V. Pallardó ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Adenosine Receptors ◽  
Spinocerebellar Ataxia Type ◽  
European Medicines Agency ◽  
Receptor Subtypes ◽  
Motor Symptoms ◽  
Spinocerebellar Ataxia Type 3 ◽  
Adenosine 2A Receptor ◽  
Type 3

: The approval of istradefylline, an adenosine 2A receptor (A2AR) antagonist, as an add-on treatment in adult patients with Parkinson’s disease by the Food and Drug Administration (FDA) and European Medicines Agency (EMA), is the latest proof of the importance of the adenosinergic system in the nervous system. Adenosine is an endogenous purine nucleoside with a role as a modulator of both neurotransmission and the inflammatory response. As such, the expression pattern of the 4 adenosine receptors (A1R, A2AR, A2BR and A3R) and the extracellular adenosine levels have attracted great interest in the pathogenesis and possible treatment of rare neurodegenerative diseases with motor symptoms. These include Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), restless legs syndrome (RLS) and Machado-Joseph disease (MJD, also known as spinocerebellar ataxia type 3, SCA3). In this review, we shall focus on the role of the different adenosine receptor subtypes in the development and possible treatment of the aforementioned rare neurodegenerative diseases with motor symptoms using the currently available data. The last section discusses the possibility of a role for the adenosine receptors in the treatment of other rare diseases based on the available molecular pathology knowledge.

scholarly journals Activation of NTS A2a adenosine receptors differentially resets baroreflex control of renal vs. adrenal sympathetic nerve activity

2009 ◽  
Vol 296 (4) ◽  
pp. H1058-H1068 ◽  
Author(s):  
Tomoko K. Ichinose ◽  
Donal S. O'Leary ◽  
Tadeusz J. Scislo
Keyword(s):  
Receptor Antagonist ◽  
Adenosine Receptors ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Response Curves ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
A2a Adenosine Receptors ◽  
Stimulation Of

The role of nucleus of solitary tract (NTS) A2a adenosine receptors in baroreflex mechanisms is controversial. Stimulation of these receptors releases glutamate within the NTS and elicits baroreflex-like decreases in mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), whereas inhibition of these receptors attenuates HR baroreflex responses. In contrast, stimulation of NTS A2a adenosine receptors increases preganglionic adrenal sympathetic nerve activity (pre-ASNA), and the depressor and sympathoinhibitory responses are not markedly affected by sinoaortic denervation and blockade of NTS glutamatergic transmission. To elucidate the role of NTS A2a adenosine receptors in baroreflex function, we compared full baroreflex stimulus-response curves for HR, RSNA, and pre-ASNA (intravenous nitroprusside/phenylephrine) before and after bilateral NTS microinjections of selective adenosine A2a receptor agonist (CGS-21680; 2.0, 20 pmol/50 nl), selective A2a receptor antagonist (ZM-241385; 40 pmol/100 nl), and nonselective A1 + A2a receptor antagonist (8-SPT; 1 nmol/100 nl) in urethane/α-chloralose anesthetized rats. Activation of A2a receptors decreased the range, upper plateau, and gain of baroreflex-response curves for RSNA, whereas these parameters all increased for pre-ASNA, consistent with direct effects of the agonist on regional sympathetic activity. However, no resetting of baroreflex-response curves along the MAP axis occurred despite the marked decreases in baseline MAP. The antagonists had no marked effects on baseline variables or baroreflex-response functions. We conclude that the activation of NTS A2a adenosine receptors differentially alters baroreflex control of HR, RSNA, and pre-ASNA mostly via non-baroreflex mechanism(s), and these receptors have virtually no tonic action on baroreflex control of these sympathetic outputs.

Cardiac effects of adenosine in A2A receptor knockout hearts: uncovering A2B receptors

2002 ◽  
Vol 282 (2) ◽  
pp. H437-H444 ◽  
Author(s):  
R. Ray Morrison ◽  
M. A. Hassan Talukder ◽  
Catherine Ledent ◽  
S. Jamal Mustafa
Keyword(s):  
Adenosine Receptor ◽  
Coronary Flow ◽  
Receptor Activation ◽  
Receptor Subtypes ◽  
Functional Responses ◽  
Response Curves ◽  
Cgs 21680 ◽  
A2a Receptor ◽  
Developed Pressure ◽  
Adenosine Receptor Activation

To clarify the relative roles of A2 adenosine receptor subtypes in the regulation of coronary flow and myocardial contractility, coronary vascular and functional responses to adenosine and its analogs were examined in isolated wild-type (WT) and A2A receptor knockout (A2AKO) mouse hearts. Nonselective agonists adenosine and 5′- N-ethyl-carboxamido-adenosine (NECA) increased coronary flow in A2AKO hearts, albeit with a rightward shift of concentration-response curves and decreased maximal vasodilation compared with WT hearts. 2- p-(2-Carboxy-ethyl)phenethylamino-5′- N-ethyl-carboxamidoadenosine (CGS-21680, a selective A2A receptor agonist) increased coronary flow in WT hearts but did not affect A2AKO hearts. Adenosine and NECA each elicited equal maximal increases in developed pressure in WT and A2AKO hearts, whereas CGS-21680 did not affect developed pressure in A2AKO hearts. Alloxazine, a selective A2B receptor antagonist, attenuated NECA-induced coronary vasodilation (from 202 ± 14% to 128 ± 9% of baseline, P < 0.05) and NECA-induced increases in developed pressure (from 133 ± 8% to 112 ± 7% of baseline, P < 0.05) in A2AKO hearts. Together, these findings support the conclusion that A2Badenosine receptor activation increases coronary flow and developed pressure in isolated murine hearts.

Sign in / Sign up

Export Citation Format

Share Document