β-Adrenoceptors differentially regulate vascular tone and angiogenesis of rat aorta via ERK1/2 and p38.
β-Adrenoceptors (β-ARs) modulate ERK1/2 and p38 in different cells, but little is known about the contribution of these signaling pathways to the function of β-ARs in vascular tissue. Immunoblotting analysis of rat aortic rings, primary endothelial (ECs) and smooth muscle cells (SMCs) isolated from aorta showed that β-AR stimulation with isoprenaline activated p38 in aortic rings and in both cultured cell types, whereas it had a dual effect on ERK1/2 phosphorylation, decreasing it in ECs while increasing it in SMCs. These effects were reversed by propranolol, which by itself increased p-ERK1/2 in ECs. Isoprenaline β-AR mediated vasodilation of aortic rings was potentiated by the ERK1/2 inhibitor, U0126, in the presence or absence of endothelium or L-NAME, whereas inhibition of p38 had no impact. Isoprenaline moderately decreased sprouting from aorta rings in the Matrigel angiogenesis assay; conversely propranolol not only prevented isoprenaline inhibition, but stimulated angiogenesis. ERK1/2 inhibition decreased angiogenesis, while a dramatic stimulation was observed by p38 blockade. Our results suggest that ERK1/2 activation after β-ARs stimulation in the smooth muscle hinders the vasodilator effect of isoprenaline, but in the endothelium β-ARs decreases ERK1/2 and increases p38 activity reducing therefore angiogenesis.
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, 46100 Burjassot, Spain.
Miguel
M
Perez-Aso
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, 46100 Burjassot, Spain.
Nicla
N
Flacco
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, 46100 Burjassot, Spain.
Nuria
N
Carpena
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, 46100 Burjassot, Spain; Institut de Reconociment Molecular i Desenvolupament Tecnològic, Centre Mixte Universitat Politècnica de València - Universitat de València, Spain.
M Carmen
MC
Montesinos
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, 46100 Burjassot, Spain.
Pilar
P
D'Ocon
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, 46100 Burjassot, Spain. Electronic address: dolores.ivorra@uv.es.
M Dolores
MD
Ivorra
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; D011433:Propranolol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases
Acetylcholine chloride (PubMed CID: 6060); Angiogenesis; ERK1/2; Isoproterenol (PubMed CID: 3779); Phenylephrine hydrochloride (PubMed CID: 5284443); Propranolol hydrochloride (PubMed CID 62882); SB203580 (PubMed CID: 176155); U0126 (PubMed CID: 3006531); U46619 (PubMed CID: 5311493); Vasodilation; l-NAME (PubMEd CID: 39836); p38; β-Adrenoceptors