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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:Several vasoactive drugs that lower blood pressure and increase heart rate induce regional cardiotoxicity in the dog, most frequently of right coronary arteries and right atrium. The basis for this selective damage is thought to result from local changes in vascular tone and blood flow. Administration of an endothelin receptor antagonist (ETRA, SB 209670) to dogs induced damage most frequent and severe in the right coronary artery and right atrium. Because site predisposition may correlate with distribution of vasoactive receptors, the objectives of this study were to map endothelin (ET) receptor distribution and density within regions of dog heart using both gene (mRNA) and protein expression endpoints for dog ET(A) and ET(B) receptors, and, additionally, correlate ET receptor subtype density with regional cardiac blood flow. A 10- to 15-mmHg reduction in mean arterial pressure with a concomitant increase in heart rate (10-20%), a six- and twofold increase in regional blood flow to the right and left atrium, respectively, and acute hemorrhage, medial necrosis, and inflammation were observed in the right coronary arteries and arteries of the right atrium after ETRA infusion for 5 days. Radioligand protein binding to quantify both ET receptors in normal dog heart indicated a twofold greater density of ET receptors in atrial regions versus ventricular regions. Importantly, ET receptor density in coronary arteries was markedly (about five- to sixfold) increased above that in atrial or ventricular tissues. ET receptor subtype characterization indicated ET(B) receptors were three times more prevalent in right coronary arteries compared to left coronary arteries and in situ hybridization confirmed localization of ET(B) in vascular smooth muscle. ET(A) receptor density was comparable in right and left coronary arteries. Quantitative real-time polymerase chain reaction for ET(A) and ET(B) receptor mRNA transcripts supported the site prevalence for message distribution. Consequently, the composite of protein and message expression profiles for ET(A) and ET(B) receptors indicated a disproportionate distribution of ET(B) receptors within right coronary artery of dog and this, along with functional measures of blood flow after ETRA infusion indicated a predisposition for exaggerated pharmacological responses and subsequent damage to right coronary arteries by ET and/or ETRAs.

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Distribution and relative expression of vasoactive receptors on arteries.

Publications

Distribution and relative expression of vasoactive receptors on arteries.

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