Local administration of ETA (but not ETB) blockers into the PAG area of the brain decreases blood pressure of DOCA-salt rats

Clara Di Filippo; Michele D'Amico; Elena Piegari; Barbara Rinaldi; Amelia Filippelli; Francesco Rossi

doi:10.1007/s00210-002-0566-6

Local administration of ETA (but not ETB) blockers into the PAG area of the brain decreases blood pressure of DOCA-salt rats

Naunyn Schmiedebergs Arch Pharmacol. 2002 Aug;366(2):123-6. doi: 10.1007/s00210-002-0566-6. Epub 2002 Jun 11.

Authors

Clara Di Filippo¹, Michele D'Amico, Elena Piegari, Barbara Rinaldi, Amelia Filippelli, Francesco Rossi

Affiliation

¹ Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Research Center for Cardiovascular Diseases, Faculty of Medicine and Surgery, Second University of Naples, Via Costantinopoli 16, Italy.

PMID: 12122498
DOI: 10.1007/s00210-002-0566-6

Abstract

The present study investigated the role possibly played by ET-receptor antagonism at periaqueductal grey (PAG) area level in decreasing the arterial blood pressure and heart rate values reached in DOCA-salt hypertensive rats. A 3-week DOCA-salt treatment induced an increase in blood pressure of up to 174+/-3 mmHg in Sprague-Dawley (SD) rats. This was paralleled by a significant increase in heart rate (HR), and endothelin-1 (ET-1) levels throughout the brain, as assessed by specific EIA ( P<0.05). In contrast, a 40% reduction of ETA mRNA levels into the brain was detected through RT-PCR. The basal MABP of DOCA rats was significantly modified by PAG injections of FR139317, an ETA receptor antagonist, or SB209670, an ETA/ETB receptor antagonist. BQ-788, an ETB receptor antagonist, was found to have no effect on blood pressure levels, while FR139317 and SB209670 also led to a significantly modified HR. PAG-endothelin ETA antagonism can therefore be said to counteract the cardiovascular changes induced by DOCA-salt treatment in rats.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Animals
Antihypertensive Agents / pharmacology*
Azepines / pharmacology
Blood Pressure / drug effects*
Desoxycorticosterone / pharmacology*
Electrophoresis, Agar Gel
Endothelin Receptor Antagonists*
Endothelin-1 / analysis
Endothelin-1 / biosynthesis
Glyceraldehyde-3-Phosphate Dehydrogenases / analysis
Glyceraldehyde-3-Phosphate Dehydrogenases / biosynthesis
Heart Rate / drug effects
Hypertension / chemically induced
Hypertension / drug therapy
Indans / pharmacology
Indoles / pharmacology
Male
Oligopeptides / pharmacology
Periaqueductal Gray / drug effects*
Piperidines / pharmacology
RNA, Messenger / biosynthesis
RNA, Messenger / drug effects
Rats
Rats, Sprague-Dawley
Receptor, Endothelin A
Receptor, Endothelin B
Reverse Transcriptase Polymerase Chain Reaction

Substances

Antihypertensive Agents
Azepines
Endothelin Receptor Antagonists
Endothelin-1
Indans
Indoles
Oligopeptides
Piperidines
RNA, Messenger
Receptor, Endothelin A
Receptor, Endothelin B
1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-
FR 139317
Desoxycorticosterone
BQ 788
Glyceraldehyde-3-Phosphate Dehydrogenases