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Naunyn Schmiedebergs Arch Pharmacol. 2002 Aug;366(2):123-6. Epub 2002 Jun 11.

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

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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.


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.

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