Anandamide-Induced Depressor Effect in Spontaneously Hypertensive Rats

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Abstract
To test the hypothesis that activation of the vanilloid receptor (VR1) contributes to the anandamide-induced depressor effect in spontaneously hypertensive rats (SHR), we used a selective VR1 antagonist capsazepine (CAPZ) and a selective cannabinoid type 1 receptor antagonist SR141716A in conjunction with a VR1 agonist capsaicin in both SHR and Wistar-Kyoto rats (WKY). Mean arterial pressure was increased in SHR compared with WKY (P<0.05). Intravenous administration of capsaicin caused a greater depressor response in SHR compared with WKY (P<0.05), which was blocked by ≈60% by CAPZ (P<0.05) in SHR only. Methanandamide caused a similar greater depressor response (P<0.05), which was blocked by ≈50% and 60% by CAPZ and SR141716A, respectively, in SHR (P<0.05) but not in WKY. Radioimmunoassay showed that methanandamide increased plasma calcitonin gene-related peptide (CGRP) levels from baseline in both SHR and WKY (P<0.05), with no difference between 2 strains. Western blot showed that protein expression for ...