Article date: July 2005
By: Grzegorz Kwolek, Agnieszka Zakrzeska, Eberhard Schlicker, Manfred Göthert, Grzegorz Godlewski, Barbara Malinowska in Volume 145, Issue 5, pages 567-575
We wanted to search for the mechanism(s) responsible for the brief pressor response induced by anandamide in urethane‐anaesthetized rats.
The anandamide‐induced pressor effect was not modified by the antagonists of cannabinoid CB1 and vanilloid TRPV1 receptors, SR 141716A (3 μmol kg−1) and capsazepine (1 μmol kg−1), respectively, by bilateral vagotomy and by pithing. Replacement of urethane by pentobarbitone virtually abolished the pressor effect of anandamide, both in pithed and vagotomized and in ‘intact’ rats (i.e. not treated in this manner).
The pressor effect of anandamide was reduced by the nonselective TRPV family inhibitor ruthenium red (3 μmol kg−1) and by the blocker of L‐type calcium channels nifedipine (1 μmol kg−1), both in pithed urethane‐anaesthetized rats and in ‘intact’ urethane‐anaesthetized rats. The nonselective β‐adrenoceptor antagonist propranolol (0.1 or 0.3 μmol kg−1) and the nonselective NMDA receptor antagonist MK‐801 (1 μmol kg−1) diminished the anandamide‐induced vasopressor response in ‘intact’ but not in pithed rats. The inhibitory effect of propranolol in ‘intact’ rats was mimicked by the β2‐adrenoceptor antagonist ICI 118551 (1 μmol kg−1), but not by the β1‐adrenoceptor antagonist CGP 20712 (1 μmol kg−1).
The present study revealed that two mechanisms may be responsible for the anandamide‐induced pressor response in urethane‐anaesthetized rats. The first involves the central nervous system (probably the medulla oblongata) and is sensitive to propranolol and MK‐801. The second, which is located peripherally (most probably in blood vessels), is sensitive to nifedipine, ruthenium red and pentobarbitone and, hence, probably represents a Ca2+‐dependent mode of action.
We wanted to search for the mechanism(s) responsible for the brief pressor response induced by anandamide in urethane‐anaesthetized rats.
The anandamide‐induced pressor effect was not modified by the antagonists of cannabinoid CB1 and vanilloid TRPV1 receptors, SR 141716A (3 μmol kg−1) and capsazepine (1 μmol kg−1), respectively, by bilateral vagotomy and by pithing. Replacement of urethane by pentobarbitone virtually abolished the pressor effect of anandamide, both in pithed and vagotomized and in ‘intact’ rats (i.e. not treated in this manner).
The pressor effect of anandamide was reduced by the nonselective TRPV family inhibitor ruthenium red (3 μmol kg−1) and by the blocker of L‐type calcium channels nifedipine (1 μmol kg−1), both in pithed urethane‐anaesthetized rats and in ‘intact’ urethane‐anaesthetized rats. The nonselective β‐adrenoceptor antagonist propranolol (0.1 or 0.3 μmol kg−1) and the nonselective NMDA receptor antagonist MK‐801 (1 μmol kg−1) diminished the anandamide‐induced vasopressor response in ‘intact’ but not in pithed rats. The inhibitory effect of propranolol in ‘intact’ rats was mimicked by the β2‐adrenoceptor antagonist ICI 118551 (1 μmol kg−1), but not by the β1‐adrenoceptor antagonist CGP 20712 (1 μmol kg−1).
The present study revealed that two mechanisms may be responsible for the anandamide‐induced pressor response in urethane‐anaesthetized rats. The first involves the central nervous system (probably the medulla oblongata) and is sensitive to propranolol and MK‐801. The second, which is located peripherally (most probably in blood vessels), is sensitive to nifedipine, ruthenium red and pentobarbitone and, hence, probably represents a Ca2+‐dependent mode of action.
British Journal of Pharmacology (2005) 145, 567–575. doi:10.1038/sj.bjp.0706195
DOI: 10.1038/sj.bjp.0706195
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