Characterization of Beta3-Adrenoceptors in Human Internal Mammary Artery and Putative Involvement in Coronary Artery Bypass Management

Rozec, Bertrand; Serpillon, Sabrina; Toumaniantz, Gilles; Seze, C De; Rautureau, Yohann; Baron, Olivier; Noireaud, Jacques; Gauthier, Chantal

doi:10.1016/j.jacc.2005.03.061

Cited by 23 publications

(20 citation statements)

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“…This could additionally and partially mask any effective relaxation activities in response to different substances. Recently, a spontaneous time-dependent relaxation of IMA control rings was observed as well [21]. In agreement with our findings, concentration-dependent relaxation by ANP in several human arteries pre-constricted with noradrenaline or prostaglandin F 2α was reported by Hughes et al [22], whereas ANP, as in our present study, was without effect on SVs.…”

Section: Discussionsupporting

confidence: 94%

“…ANP induced greater relaxation and cGMP concentrations in pulmonary arteries pre-constricted with endothelin-1 than in the veins. CNP was more potent in the veins, but caused only moderate cGMP production, and a cGMPindependent mechanism of CNP-induced relaxation was speculated [21]. On the other hand, dose-dependent increases in intracellular cGMP concentrations were shown after NP (ANP, BNP or CNP) or SNP stimulation in membrane preparations of rat thoracic aorta [27].…”

Section: Discussionmentioning

confidence: 98%

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Direct comparison of relaxation and cGMP production in human coronary by-pass grafts in response to stimulation with natriuretic peptides and a nitric oxide donor

et al. 2006

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In the present study, we investigated the vasodilator properties of A-type, B-type and C-type natriuretic peptides (ANP, BNP and CNP respectively) and the NO (nitric oxide) donor sin-1 (3-morpholino-sydnonimine) in human by-pass grafts. In contrast with previous studies, the same vessel was used to demonstrate a direct link between cGMP production and functional relaxation. Remnants of the IMA (internal mammary artery) and SV (saphenous vein) were obtained from 82 patients undergoing coronary artery by-pass grafting. The responses to cumulative concentrations of ANP, BNP, CNP and sin-1 in vessel rings pre-contracted with a thromboxane A2 agonist (U46619) were measured in an organ bath. Additionally, intracellular cGMP production after single submaximal dose application of these drugs to vessel rings was determined by a RIA. ANP (P=0.001) and sin-1 (P<0.001) caused significant concentration-dependent relaxation of the IMA. In the SV, only sin-1 (P<0.001) induced marked concentration-dependent relaxation. At a single submaximal concentration, significant relaxation as well as intracellular cGMP production were found in response to ANP, BNP and sin-1 in the IMA. In contrast, in the SV, only sin-1 significantly induced cGMP production and relaxation. There was a moderate, but significant, correlation between intracellular cGMP net production and net relaxation in the IMA. In conclusion, ANP, as the most powerful relaxant of all the natriuretic peptides tested on the IMA, may be a possible alternative vasorelaxant to overcome peri-operative vasospasm in this artery. In contrast with sin-1, ANP and BNP were not effective vasorelaxants of the SV. Net relaxation in response to natriuretic peptides correlated with cGMP net concentrations in the IMA.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 98%

Direct comparison of relaxation and cGMP production in human coronary by-pass grafts in response to stimulation with natriuretic peptides and a nitric oxide donor

et al. 2006

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“…Interestingly, recent evidences suggest that Adrb1 appear to be mainly responsible for vasorelaxation in mouse (Chruscinski et al, 2001) and rat mesenteric resistance arteries (MRA) (Briones et al, 2005), and mediate smooth muscle hyperpolarization in rat MRA (Garland et al, 2011). In addition, the participation of Adrb3 in the vasorelaxant response has also been documented in some blood vessels, such as the rat carotid artery (Oriowo, 1994), rat (Sooch and Marshall, 1997) and canine (Tagaya et al, 1999) pulmonary artery, the human internal mammary (Rozec et al, 2005) and placental (Rouget et al, 2006) arteries, and also in coronary microarteries (Dessy et al, 2004). Nevertheless, there have been conflicting reports on Adrb3 involvement in vasodilator responses in rat aorta.…”

Section: Introductionmentioning

confidence: 99%

Different β‐adrenoceptor subtypes coupling to cAMP or NO/cGMP pathways: implications in the relaxant response of rat conductance and resistance vessels

Flacco

Segura

Pérez-Aso

et al. 2013

British J Pharmacology

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Figure 3 amended [23 January 2015] to correct error in text. BACKGROUND AND PURPOSETo analyse the relative contribution of b1-, b2-and b3-adrenoceptors (Adrb) to vasodilatation in conductance and resistance vessels, assessing the role of cAMP and/or NO/cGMP signalling pathways. EXPERIMENTAL APPROACHRat mesenteric resistance artery (MRA) and aorta were used to analyse the Adrb expression by real-time-PCR and immunohistochemistry, and for the pharmacological characterization of Adrb-mediated activity by wire myography and tissue nucleotide accumulation. KEY RESULTSThe mRNAs and protein for all Adrb were identified in endothelium and/or smooth muscle cells (SMCs) in both vessels. In MRA, Adrb1 signalled through cAMP, Adrb3 through both cAMP and cGMP, but Adrb2, did not activate nucleotide formation; isoprenaline relaxation was inhibited by propranolol (b1, b2), CGP20712A (b1), and SQ22536 (adenylyl cyclase inhibitor), but not by ICI118,551 (b2), SR59230A (b3), ODQ (soluble guanylyl cyclase inhibitor), L-NAME or endothelium removal. In aorta, Adrb1 signalled through cAMP, while b2-and b3-subtypes through cGMP; isoprenaline relaxation was inhibited by propranolol, ICI118,551, ODQ, L-NAME, and to a lesser extent, by endothelium removal. CL316243 (b3-agonist) relaxed aorta, but not MRA. CONCLUSION AND IMPLICATIONDespite all three Adrb subtypes being found in both vessels, Adrb1, located in SMCs and acting through the adenylyl cyclase/cAMP pathway, are primarily responsible for vasodilatation in MRA. However, Adrb-mediated vasodilatation in aorta is driven by endothelial Adrb2 and Adrb3, but also by the Adrb2 present in SMCs, and is coupled to the NO/cGMP pathway. These results could help to understand the different physiological roles played by Adrb signalling in regulating conductance and resistance vessels.

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“…In recent years, expression of the protein was also found in the human heart (Rozec and Gauthier, 2006), mammary artery (Rozec et al, 2005), placental artery (Rouget et al, 2006), gastrointestinal tract (Anthony et al, 2000), prostate and gall bladder (de Matteis et al, 2002), urinary bladder detrusor (Igawa et al, 1999) and brain (Rodriguez et al, 1995).…”

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confidence: 98%

Distribution and quantification of β-3 adrenergic receptor in tissues of sheep

Liu

et al. 2011

Animal

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The b-3 adrenergic receptor (ADRB3) is a G-protein coupled receptor involved in regulating lipolysis, as part of homeostatic regulation. In this study, South African Mutton Merino and Shanxi Dam Line were used to study the distribution and quantification of ADRB3 in adipose (subcutaneous, omental, retroperitoneal, mesenteric and perirenal fat) and non-adipose (heart, liver, spleen, lung and kidney) tissues of sheep. The protein was determined by immunohistochemical technique and by mRNA abundance via real-time polymerase chain reaction. ADRB3 was detected in all studied tissues with abundance in adipose tissues higher than in non-adipose tissues ( P , 0.001). For adipose tissues, greater expression was found in deep deposits such as great omental and retroperitoneal fat than in subcutaneous fat ( P , 0.05). Significant differences ( P , 0.05) both for mRNA and for protein expression also existed between the two sheep flocks. These findings are consistent with the known function of ADRB3 in mediating lipolysis and homeostasis in adipose tissues.Keywords: b-3 adrenergic receptor, sheep, tissues, mRNA expression, immunohistochemistry ImplicationsIn this study, the b-3 adrenergic receptor (ADRB3) expression in various tissues of sheep was detected by immunohistochemical technique and by mRNA abundance via real-time PCR. Despite its low expression, the presence of ADRB3 in the spleen and kidney was found in livestock for the first time. Generally, ADRB3 expressed higher in adipose than in non-adipose tissues, and for the former, it was higher in deep fat deposits than in subcutaneous fat. The distributions are consistent with the known functions of ADRB3 in mediating lipolysis and homeostasis in adipose tissues, and relaxation of vascular smooth muscle in the cardiovascular system. The relation between low expression and its function in some viscera, for example, lung, spleen and kidney of sheep deserves further study.Introduction b-Adrenergic receptors (ADRBs) are G-protein coupled receptors that mediate effects of the endogenous catecholamines adrenaline and noradrenaline. Three subtypes of ADRBs have been identified, named ADRB1, ADRB2 and ADRB3, respectively. These receptors are present in most mammalian tissues, but the distribution of each subtype varies among tissues in a given species. Among the various physiological roles of ADRBs, the ADRB3 subtype mediates lipolysis and stimulates thermogenesis in adipose tissues (Cannon and Nedergaard, 2004) by activating uncoupling protein in mitochondria.In early studies, ADRB3 was identified mainly on the surface of white and brown adipocytes as reviewed by Strosberg (1997). In recent years, expression of the protein was also found in the human heart (Rozec and Gauthier , (Rodriguez et al., 1995).It has been confirmed that the mRNA of the ADRB3 gene is expressed in various tissues of domestic animals. The 2.0 kb ADRB3 transcript in the bovine brown adipose tissue (PietriRouxel et al., 1995), and two transcripts of 2.2 and 1.9 kb in porcine subcutaneous fat (McNeel and ...

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Characterization of Beta3-Adrenoceptors in Human Internal Mammary Artery and Putative Involvement in Coronary Artery Bypass Management

Abstract: Those results demonstrated the presence of beta3-ARs in the endothelial layer of human IMA. The present work highlights the role of beta3-ARs in vasomotor control of IMA and opens new fields of investigation in coronary bypass graft management, heart failure, and hypertension.

Cited by 23 publications

References 43 publications

Direct comparison of relaxation and cGMP production in human coronary by-pass grafts in response to stimulation with natriuretic peptides and a nitric oxide donor

Direct comparison of relaxation and cGMP production in human coronary by-pass grafts in response to stimulation with natriuretic peptides and a nitric oxide donor

Different β‐adrenoceptor subtypes coupling to cAMP or NO/cGMP pathways: implications in the relaxant response of rat conductance and resistance vessels

Distribution and quantification of β-3 adrenergic receptor in tissues of sheep

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