Relaxation by adenosine and its analogs of potassium-contracted human coronary arteries

Sabouni, M H; Ramagopal, Mudumbi V.; Mustafa, S. Jamal

doi:10.1007/bf00180667

Cited by 18 publications

(10 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adenosine is well known to play a vasoregulatory role in human coronary arteries (16,17,62,63). We and others (5,63,67,69) have also previously demonstrated the pivotal role of A 2A ARs in CF regulation.…”

Section: Discussionsupporting

confidence: 51%

“…The activation of A 1 ARs results in negative chronotropic and ionotropic effects and a decrease in coronary flow (CF) (68), whereas other studies have suggested that the activation of both A 1 ARs or A 3 ARs before ischemia is cardioprotective (6,30). However, adenosine has been shown to play a vasoregulatory role in human coronary arteries (16,17,62,63). It is well established that the activation of A 2A ARs induces positive inotropic effects and that A 2A ARs play a major role in the regulation of CF in ex vivo models (67,69).…”

Section: Sanjani Ms Teng B Krahn T Tilley S Ledent C Mustafa Sjmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Contributions of A_2Aand A_2Badenosine receptors in coronary flow responses in relation to the K_ATPchannel using A_2Band A_2A/2Bdouble-knockout mice

Sanjani

Teng

Krahn

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Sanjani MS, Teng B, Krahn T, Tilley S, Ledent C, Mustafa SJ. Contributions of A 2A and A2B adenosine receptors in coronary flow responses in relation to the KATP channel using A2B and A2A/2B doubleknockout mice. Am J Physiol Heart Circ Physiol 301: H2322-H2333, 2011. First published September 23, 2011 doi:10.1152/ajpheart.00052.2011.-Adenosine plays a role in physiological and pathological conditions, and A 2 adenosine receptor (AR) expression is modified in many cardiovascular disorders. In this study, we elucidated the role of the A2BAR and its relationship to the A2AAR in coronary flow (CF) changes using A2B single-knockout (KO) and A2A/2B double-KO (DKO) mice in a Langendorff setup. We used two approaches: 1) selective and nonselective AR agonists and antagonists and 2) A2AKO and A 2BKO and A2A/2BDKO mice. BAY 60-6583 (a selective A2B agonist) had no effect on CF in A2BKO mice, whereas it significantly increased CF in wild-type (WT) mice (maximum of 23.3 Ϯ 9 ml·min ). NECA did not induce any increase in CF in A2A/2BDKO mice, whereas a significant increase was observed in WT mice (maximum of 23.1 Ϯ 2.1 ml·min). Furthermore, the mitochondrial ATP-sensitive K ϩ (KATP) channel blocker 5-hydroxydecanoate had no effect on the NECAinduced increase in CF in WT mice, whereas the NECA-induced increase in CF in WT (17.6 Ϯ 2 ml·min Ϫ1 ·g Ϫ1 ), A2AKO (12.5 Ϯ 2.3 ml·min , respectively). In conclusion, this is the first evidence supporting the compensatory upregulation of A2AARs in A2BKO mice and demonstrates that both A2AARs and A2BARs induce CF changes through KATP channels. These results identify AR-mediated CF responses that may lead to better therapeutic approaches for the treatment of cardiovascular disorders. isolated mouse heart; A2B knockout mice; ATP-sensitive K ϩ channel ADENOSINE is an endogenous nucleoside that is released through the breakdown of adenine nucleotides. The cardiovascular effects of adenosine are mediated through the activation of its four subtypes of receptors (ARs), namely, A 1 , A 2A , A 2B , and A 3 . The activation of A 1 ARs results in negative chronotropic and ionotropic effects and a decrease in coronary flow (CF) (68), whereas other studies have suggested that the activation of both A 1 ARs or A 3 ARs before ischemia is cardioprotective (6, 30). However, adenosine has been shown to play a vasoregulatory role in human coronary arteries (16,17,62,63

show abstract

Section: Discussionsupporting

confidence: 51%

Section: Sanjani Ms Teng B Krahn T Tilley S Ledent C Mustafa Sjmentioning

confidence: 99%

See 1 more Smart Citation

Contributions of A_2Aand A_2Badenosine receptors in coronary flow responses in relation to the K_ATPchannel using A_2Band A_2A/2Bdouble-knockout mice

Sanjani

Teng

Krahn

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…In several human vascular beds, adenosine A 2 receptors mediate vasodilatation in part through endothelium, possibly by releasing NO (Sobrevia et al, 1997;Li et al, 1998) and prostacyclin (Chiang et al, 1994;Donoso et al, 2005). Other studies, however, failed to demonstrate endothelium-dependent responses in the presence of adenosine (Sabouni et al, 1990;Tsai et al, 1996;Kemp and Cocks, 1999). Controversy also exists on the receptor subtype (A 2A or A 2B ) predominating on endothelial cells (Chiang et al, 1994;Iwamoto et al, 1994;Sobrevia et al, 1997;Li et al, 1998;Donoso et al, 2005).…”

mentioning

confidence: 92%

Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A_2BReceptor Dysfunction

Faria

Magalhães-Cardoso²,

Lafuente-de-Carvalho³

et al. 2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Although adenosine has been implicated in penile erection in human males, the receptor subtype responsible for adenosine regulation of human corpus cavernosum (HCC) smooth muscle tone is still a matter of debate. Using selective adenosine agonists and antagonists, we aimed at characterizing the adenosine receptors mediating relaxation of precontracted (with 1 M phenylephrine) HCC strips. HCC specimens were collected from control subjects (organ donors) and from patients with severe vasculogenic erectile dysfunction (ED). In control subjects, adenosine and 5Ј-N-ethyl-carboxamide adenosine (NECA) fully relaxed HCC. The selective A 2A receptor agonist 2-[4-(2-p-carboxy ethyl)phenylamino]-5Ј-N-ethylcarboxamido adenosine (CGS21680C) produced only a partial relaxation (30 -50%) of HCC, which could be further enhanced by simultaneous application of 100 M NECA. The selective A 2B receptor antagonist N-(4-acetylphenyl)-2- [4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-il) (ZM241385) (50 nM) consistently reduced the actions of both agonists. In contrast to CGS21680C, NECAinduced relaxation was attenuated when endothelial production of NO and prostanoids was reduced by 100 M N G -nitro-Larginine and 10 M indomethacin, respectively. HCC strips from patients with vasculogenic ED were partially resistant to NECA but kept relaxation to CGS21680C; the remaining effect was sensitive to blockade of A 2A receptors with 50 nM ZM241385. Data suggest that adenosine regulates HCC smooth muscle tone through the activation of two receptor populations, CGS21680C-sensitive (A 2A ) and -insensitive (A 2B ) receptors, located on smooth muscle fibers and on endothelial cells, respectively. Endothelial dysfunction may be correlated with a loss of adenosine A 2B receptor activity in penile vessels from men with vasculogenic ED.

show abstract

“…A 2 receptors (according to the old nomenclature used by Fredholm et al, 1994) are implicated in many vessels in the hypotensive activity of adenosine, due to the presence of speci®c membrane receptors in many vessels (Rongen et al,described in porcine coronary vasculature (Abebe et al, 1995), while an endothelium-independent A 2 -receptormediated vasodilation is reported in human and guinea-pig coronaries (Sabouni et al, 1990;Vials & Burnstock, 1993). As regards the particular A 2 receptor subtype involved in the adenosine-mediated hypotension, there are di erent indications: A 2a receptors are reported to mediate relaxation of rat aorta and bovine, rat and pig coronary artery (Hutchison et al, 1989;Conti et al, 1993) while A 2b receptors mediate adenosine-induced relaxation in guinea-pig pulmonary artery (Szentmiklosi et al, 1995) and rat mesenteric arterial bed (Rubino et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Adenosine‐mediated hypotension in in vivo guinea‐pig: receptors involved and role of NO

Nieri¹,

Martinotti²,

Calderone³

et al. 2001

British J Pharmacology

View full text Add to dashboard Cite

1 Adenosine produced a biphasic lowering of the mean BP with a drastic bradycardic e ect at the highest doses. The ®rst phase hypotensive response was signi®cantly reduced by the nitric oxide (NO) synthase inhibitor L-NAME. 2 The A 2a /A 2b agonist NECA produced hypotensive and bradycardic responses similar to those elicited by adenosine, which were not signi®cantly modi®ed by the A 2b antagonist enprofylline. 3 The A 2a agonist CGS 21680 did not signi®cantly in¯uence basal HR while induced a hypotensive response antagonized by the A 2a selective antagonist ZM 241385, and reduced by both L-NAME and the guanylate cyclase inhibitor methylene blue. 4 The A 1 agonist R-PIA showed a dose-dependent decrease in BP with a drastic decrease in HR at the highest doses. The A 1 selective antagonist DPCPX signi®cantly reduced the bradycardic activity and also the hypotensive responses obtained with the lowest doses while it increased those obtained with the highest ones. 5 The A 1 /A 3 agonist APNEA, in the presence of the xanthinic non-selective antagonist 8-pSPT, maintained a signi®cant hypotensive, but not bradycardic, activity, not abolished by the histamine antagonist diphenhydramine. 6 The selective A 3 agonist IB-MECA revealed a weak hypotensive and bradycardic e ect, but only at the highest doses. 7 In conclusion, in the systemic cardiovascular response to adenosine two major components may be relevant: an A 2a -and NO-mediated hypotension, and a bradycardic e ect with a consequent hypotension, via atypical A 1 receptors. Finally, an 8-pSPT-resistant hypotensive response not attributable to A 3 receptor-stimulation or to release of histamine by mastocytes or other immune cells was observed. IntroductionFour classes of membrane surface adenosine receptors are described, de®ned A 1 , A 2a , A 2b and A 3 , through which the nucleoside in¯uences many functions in humans and other animals (Ralevic & Burnstock, 1998). As far as the cardiovascular system is concerned, adenosine slows heart rate (HR) and atrioventricular conduction and antagonizes the cardio-stimulatory e ects of catecholamines via cardiac A 1 receptors in di erent mammals (Belardinelli et al., 1989;Olsson & Pearson, 1990). An increase in blood pressure (BP) and HR has been described in rats and in cats via central A 1 receptors (St Lambert et al., 1994; SilvaCarvalho et al., 1993). In contrast, a dose-related decrease in BP and HR is observed after microinjection of adenosine into the caudal nucleus of tractus solitarii in the rat (Lo et al., 1998).As regards a direct e ect on blood vessels, A 1 purinoceptors mediate vasodilation in the porcine coronary artery (Merkel et al., 1992) but they are involved, on the contrary, in vasoconstrictor responses, i.e. in the rat kidney (Jackson, 1991), in guinea-pig pulmonary artery and aorta (Biaggioni et al., 1989;Stoggall & Shaw, 1990) and in hamster skin (Stojanov & Proctor, 1990;Proctor & Stojanov, 1991).Moreover, a signi®cant role of A 1 receptors in the regulation of BP also appears to be linked to a prejunction...

show abstract

Relaxation by adenosine and its analogs of potassium-contracted human coronary arteries

Cited by 18 publications

References 8 publications

Contributions of A_2Aand A_2Badenosine receptors in coronary flow responses in relation to the K_ATPchannel using A_2Band A_2A/2Bdouble-knockout mice

Contributions of A_2Aand A_2Badenosine receptors in coronary flow responses in relation to the K_ATPchannel using A_2Band A_2A/2Bdouble-knockout mice

Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A_2BReceptor Dysfunction

Adenosine‐mediated hypotension in in vivo guinea‐pig: receptors involved and role of NO

Contact Info

Product

Resources

About

Relaxation by adenosine and its analogs of potassium-contracted human coronary arteries

Cited by 18 publications

References 8 publications

Contributions of A2Aand A2Badenosine receptors in coronary flow responses in relation to the KATPchannel using A2Band A2A/2Bdouble-knockout mice

Contributions of A2Aand A2Badenosine receptors in coronary flow responses in relation to the KATPchannel using A2Band A2A/2Bdouble-knockout mice

Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A2BReceptor Dysfunction

Adenosine‐mediated hypotension in in vivo guinea‐pig: receptors involved and role of NO

Contact Info

Product

Resources

About

Contributions of A_2Aand A_2Badenosine receptors in coronary flow responses in relation to the K_ATPchannel using A_2Band A_2A/2Bdouble-knockout mice

Contributions of A_2Aand A_2Badenosine receptors in coronary flow responses in relation to the K_ATPchannel using A_2Band A_2A/2Bdouble-knockout mice

Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A_2BReceptor Dysfunction