ETA endothelin receptors are involved in the ouabain-induced haemodynamic effects in the periaqueductal gray area of rats.
The aim of the present study was to asses the effects on blood pressure and vascular resistances elicited by microinjections of ouabain (OUA) within the periaqueductal gray area (PAG). We also tested whether peripheral vascular responses caused by exogenous intra-PAG ouabain involve activation of the PAG-endothelin system. In normotensive Sprague-Dawley rats the basal mean arterial blood pressure (MABP) was 114 +/- 3 mmHg. This was significantly increased by OUA (3 micro g, 122 +/- 2 mmHg, p < 0.05; and 6 micro g, 139 +/- 3 mmHg, p < 0.01) microinjected into the PAG area. Increases in MABP were associated with increases in total peripheral resistances (TPR), organ vascular resistances, and with reduced blood flow of almost all the organs tested: kidneys, skeletal muscle, skin, stomach, spleen, testes and intestine. Cardiac output did not change. Changes in the above vascular parameters induced by OUA were significantly (p < 0.01) reduced by intra-PAG microinjections of FR139317 (a selective ETA receptor antagonist, 5 nmol), SB209670 (a non-selective ETA/ETB receptor antagonist, 3 nmol), but not by BQ 788 (a selective ETB receptor antagonist, 5 nmol). In conclusion, OUA into the PAG area of normotensive rats caused significant changes in peripheral vascular parameters that are reduced by ETA receptor antagonists. These results indicate that PAG-ET-1 system via an action on ETA receptors is involved in the OUA effects.
D'Amico
Michele
M
Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Centre of Excellence for Cardiovascular Diseases, Faculty of Medicine and Surgery, 2nd University of Naples, Via Costantinopoli 16-80138 Naples, Italy. damicomichele@hotmail.com
Di Filippo
Clara
C
Piegari
Elena
E
Rinaldi
Barbara
B
Rossi
Francesco
F
Filippelli
Amelia
A
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010042:Ouabain / Q000008:administration & dosage / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology*
D001381:Azepines; D002316:Cardiotonic Agents; D007211:Indoles; D009842:Oligopeptides; D010880:Piperidines; D017466:Receptors, Endothelin; C098996:endothelin-3 receptor; C079574:FR 139317; C086539:BQ 788; D010042:Ouabain