title: Blood pressure variability provokes vascular β-adrenoceptor desensitization in rats.
abstract: Spontaneous variation in blood pressure is defined as 'blood pressure variability' (BPV). Sinoaortic denervation (SAD) is characterized by BPV without sustained hypertension. In the present study, we investigated whether BPV could be related to vascular β-adrenoceptor desensitization in rats. Three days after surgery (SAD and control), aortic rings were placed in an organ chamber and the relaxation stimulated by β-adrenoceptor agonists, isoprenaline, terbutaline, BRL37344 and cyanopindolol was verified. The participation of intracellular nucleotides signaling pathways was also verified using forskolin, sodium nitroprusside and acetylcholine to induce relaxation. The effects of BPV on the increase in endothelial cytosolic Ca(2+) concentration stimulated by the β2-adrenoceptor agonist was examined by confocal microscopy. In addition, the vascular expression of the β2-adrenoceptor was also examined by immunohistochemistry. The results show that isoprenaline and terbutaline-induced relaxation was lower in the aortas of rats with BPV. Relaxation responses to other vasorelaxant compounds were similar in both groups of rats. Histological analysis revealed a lower level of β2-adrenoceptor and confocal microscopy showed minor cytosolic Ca(2+) concentration in endothelial cells stimulated by the β2-adrenoceptor agonist in rats with BPV. In conclusion, BPV leads to desensitization of the β2-adrenoceptor, which could contribute to worse β-adrenoceptor agonist-induced relaxation in isolated aortas.
authors.affiliation: Faculty of Pharmacy, Federal University of Goias, FF/UFG, Goiânia, GO, Brazil. Electronic address: matheusroch@yahoo.com.br.
authors.forename: Matheus L
authors.initials: ML
authors.lastname: Rocha
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Physics and Chemistry, FCFRP/USP, Ribeirão Preto, SP, Brazil.
authors.forename: Bruno R
authors.initials: BR
authors.lastname: Silva
authors.affiliation: School of Health Sciences, Faculty of Ceilandia, UNB, Brasilia, Brazil.
authors.forename: Claure N
authors.initials: CN
authors.lastname: Lunardi
authors.affiliation: Medical School, Department of Pathology and Legal Medicine, FMRP/USP, Ribeirão Preto, SP, Brazil.
authors.forename: Leandra N Z
authors.initials: LN
authors.lastname: Ramalho
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Physics and Chemistry, FCFRP/USP, Ribeirão Preto, SP, Brazil.
authors.forename: Lusiane M
authors.initials: LM
authors.lastname: Bendhack
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000294:innervation*; D017763:Autonomic Denervation / Q000379:methods*; D001794:Blood Pressure / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D066298:In Vitro Techniques; D008297:Male; D018613:Microscopy, Confocal; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2; D014665:Vasodilator Agents
keywords: Blood pressure variability; Desensitization; Relaxation; Sinoaortic denervation; β-adrenoceptor