1. Central plasmid antisense administration reduces blood pressure inhibiting alpha2B adrenoceptor gene expression in spontaneously hypertensive rats in vivo.
- Author
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Triantafyllidi H, Kintsurashvili E, Johns C, Gavras I, and Gavras H
- Subjects
- Adrenergic alpha-2 Receptor Antagonists, Animals, Blood Pressure physiology, Gene Expression, Green Fluorescent Proteins metabolism, Heart Rate physiology, Hypertension genetics, Injections, Intraventricular, Male, Oligonucleotides, Antisense administration & dosage, Oligonucleotides, Antisense genetics, Plasmids administration & dosage, Plasmids genetics, Rats, Rats, Inbred SHR, Hypertension therapy, Oligonucleotides, Antisense therapeutic use, Plasmids therapeutic use, Receptors, Adrenergic, alpha-2 genetics
- Abstract
Introduction: The involvement of central alpha2B adrenoceptors (AR) in the maintenance of hypertension has been proven by a series of previous experiments, at least in a particular model of nephrogenic salt-induced hypertension. The aim of the present study was to investigate further the role of central alpha2B AR in hypertension by applying antisense technology in another experimental model, the spontaneously hypertensive rat (SHR)., Methods: Plasmid antisense DNA against the alpha2B gene was given by intracerebroventricular injection to salt-fed SHRs, while a control group received plasmid alone., Results: There was a significant fall in blood pressure, by an average of 31 +/- 12 mmHg, within the first twenty hours after injection in the antisense group. On the first post-injection day the blood pressure fell from 204 +/- 5.3 mmHg to 176.8 +/- 2.9 mmHg (p = 0.02). However, no significant changes in blood pressure were noticed in the plasmid group. Body-weight in both groups remained stable during the experiment. A study of frozen brain sections of SHRs after antisense DNA injection suggested that the nucleus tractus solitarii was one of the expression sites, while there was no histological evidence of tissue disruption., Conclusion: Central injection of antisense DNA targeting alpha2B mRNA in the genetic model of hypertension of the SHR seems to have a significant hypotensive effect, at least on the first day of injection. The nucleus tractus solitarii seems to be the primary area of action of central alpha2B AR in SHRs.
- Published
- 2006