Local administration of ETA (but not ETB) blockers into the PAG area of the brain decreases blood pressure of DOCA-salt rats.
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.
Di Filippo
Clara
C
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.
D'Amico
Michele
M
Piegari
Elena
E
Rinaldi
Barbara
B
Filippelli
Amelia
A
Rossi
Francesco
F
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000032:analysis / Q000096:biosynthesis; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000032:analysis / Q000096:biosynthesis; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D007189:Indans / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000959:Antihypertensive Agents; D001381:Azepines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007189:Indans; D007211:Indoles; D009842:Oligopeptides; D010880:Piperidines; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-; C079574:FR 139317; D003900:Desoxycorticosterone; C086539:BQ 788; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases