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Distribution and relative expression of vasoactive receptors on arteries.

ABSTRACT: Arterial tone is regulated by multiple ligand-receptor interactions, and its dysregulation is involved in ischemic conditions such as acute coronary spasm or syndrome. Understanding the distribution of vasoactive receptors on different arteries may help guide the development of tissue-specific vasoactive treatments against arterial dysfunction. Tissues were harvested from coronary, mesenteric, pulmonary, renal and peripheral human artery (n?=?6 samples of each) and examined using a human antibody array to determine the expression of 29 vasoactive receptors and 3 endothelin ligands. Across all types of arteries, outer diameter ranged from 2.24?±?0.63 to 3.65?±?0.40 mm, and AVPR1A was the most abundant receptor. The expression level of AVPR1A in pulmonary artery was similar to that in renal artery, 2.2 times that in mesenteric artery, 1.9 times that in peripheral artery, and 2.2 times that in coronary artery. Endothelin-1 was expressed at significantly higher levels in pulmonary artery than peripheral artery (8.8 times), mesenteric artery (5.3 times), renal artery (7.9 times), and coronary artery (2.4 times). Expression of ADRA2B was significantly higher in coronary artery than peripheral artery. Immunohistochemistry revealed abundant ADRA2B in coronary artery, especially vessels with diameters below 50 ?m, but not in myocardium. ADRA2C, in contrast, was expressed in both myocardium and blood vessels. The high expression of ADRA2B in coronary artery but not myocardium highlights the need to further characterize its function. Our results help establish the distribution and relative levels of tone-related receptors in different types of arteries, which may guide artery-specific treatments.

SUBMITTER: Liu X

PROVIDER: S-EPMC7505843 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Distribution and relative expression of vasoactive receptors on arteries.

Liu Xinhao X Luo Dan D Zhang Jie J Du Lei L

Scientific reports 20200921 1

Arterial tone is regulated by multiple ligand-receptor interactions, and its dysregulation is involved in ischemic conditions such as acute coronary spasm or syndrome. Understanding the distribution of vasoactive receptors on different arteries may help guide the development of tissue-specific vasoactive treatments against arterial dysfunction. Tissues were harvested from coronary, mesenteric, pulmonary, renal and peripheral human artery (n = 6 samples of each) and examined using a human antibod ...[more]

PMID: 32958803

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Project description:AimThe importance of endothelial cell (EC) autophagy to vascular homeostasis in the context of health and disease is evolving. Earlier, we reported that intact EC autophagy is requisite to maintain shear-stress-induced nitric oxide (NO) generation via glycolysis-dependent purinergic signalling to endothelial NO synthase (eNOS). Here, we illustrate the translational and functional significance of these findings.Methods and resultsFirst, we assessed translational relevance using older male humans and mice that exhibit blunted EC autophagy and impaired arterial function vs. adult controls. Active hyperaemia evoked by rhythmic handgrip exercise-elevated radial artery shear-rate similarly from baseline in adult and older subjects for 60 min. Compared with baseline, indexes of autophagy initiation, p-eNOSS1177 activation, and NO generation, occurred in radial artery ECs obtained from adult but not older volunteers. Regarding mice, indexes of autophagy and p-eNOSS1177 activation were robust in ECs from adult but not older animals that completed 60-min treadmill-running. Furthermore, 20 dyne • cm2 laminar shear stress × 45-min increased autophagic flux, glycolysis, ATP production, and p-eNOSS1177 in primary arterial ECs obtained from adult but not older mice. Concerning functional relevance, we next questioned whether the inability to initiate EC autophagy, glycolysis, and p-eNOSS1177in vitro precipitates arterial dysfunction ex vivo. Compromised intraluminal flow-mediated vasodilation displayed by arteries from older vs. adult mice was recapitulated in vessels from adult mice by (i) NO synthase inhibition; (ii) acute autophagy impairment using 3-methyladenine (3-MA); (iii) EC Atg3 depletion (iecAtg3KO mice); (iv) purinergic 2Y1-receptor (P2Y1-R) blockade; and (v) germline depletion of P2Y1-Rs. Importantly, P2Y1-R activation using 2-methylthio-ADP (2-Me-ADP) improved vasodilatory capacity in arteries from (i) adult mice treated with 3-MA; (ii) adult iecAtg3KO mice; and (iii) older animals with repressed EC autophagy.ConclusionsArterial dysfunction concurrent with pharmacological, genetic, and age-associated EC autophagy compromise is improved by activating P2Y1-Rs.

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Distribution and relative expression of vasoactive receptors on arteries.

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Distribution and relative expression of vasoactive receptors on arteries.

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