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Vanilloid receptors on capsaicin-sensitive sensory nerves mediate relaxation to methanandamide in the rat isolated mesenteric arterial bed and small mesenteric arteries.
Br J Pharmacol. 2000 Aug; 130(7):1483-8.BJ

Abstract

In the present study, the vasodilator actions of methanandamide and capsaicin in the rat isolated mesenteric arterial bed and small mesenteric arterial segments were investigated. Methanandamide elicited concentration-dependent relaxations of preconstricted mesenteric arterial beds (pEC(50)=6.0+/-0.1, E(max)=87+/-3%) and arterial segments (pEC(50)=6.4+/-0.1, E(max)=93+/-3%). In arterial beds, in vitro capsaicin pre-treatment blocked vasorelaxation to 1 and 3 microM methanandamide, and reduced to 12+/-7% vasorelaxation to 10 microM methanandamide. Methanandamide failed to relax arterial segments pre-treated in vitro with capsaicin. In arterial beds from rats treated as neonates with capsaicin to cause destruction of primary afferent nerves, methanandamide at 1 and 3 microM did not evoke vasorelaxation, and relaxation at 10 microM methanandamide was reduced to 26+/-4%. Ruthenium red (0.1 microM), an inhibitor of vanilloid responses, attenuated vasorelaxation to methanandamide in arterial beds (pEC(50)=5.6+/-0.1, E(max)=89+/-1%). Ruthenium red at 1 microM abolished the response to 1 microM methanandamide, and greatly attenuated relaxation at 3 and 10 microM methanandamide in arterial beds. In arterial segments, ruthenium red (0.15 microM) blocked vasorelaxation to methanandamide, but not to CGRP. In arterial segments, the vanilloid receptor antagonist capsazepine (1 microM) inhibited, and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8 - 37) (3 microM) abolished, methanandamide-induced relaxations. CGRP(8 - 37), but not capsazepine, attenuated significantly relaxation to exogenous CGRP. These data show that capsaicin and ruthenium red attenuate vasorelaxation to methanandamide in the rat isolated mesenteric arterial bed and small mesenteric arterial segments. In addition, CGRP(8 - 37) and capsazepine antagonize responses to methanandamide in mesenteric arterial segments. In conclusion, vanilloid receptors on capsaicin-sensitive sensory nerves play an important role in the vasorelaxant action of methanandamide in the rat isolated mesenteric arterial bed and small mesenteric arterial segments.

Authors+Show Affiliations

School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH. vera.ralevic@nottingham.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10928948

Citation

Ralevic, V, et al. "Vanilloid Receptors On Capsaicin-sensitive Sensory Nerves Mediate Relaxation to Methanandamide in the Rat Isolated Mesenteric Arterial Bed and Small Mesenteric Arteries." British Journal of Pharmacology, vol. 130, no. 7, 2000, pp. 1483-8.
Ralevic V, Kendall DA, Randall MD, et al. Vanilloid receptors on capsaicin-sensitive sensory nerves mediate relaxation to methanandamide in the rat isolated mesenteric arterial bed and small mesenteric arteries. Br J Pharmacol. 2000;130(7):1483-8.
Ralevic, V., Kendall, D. A., Randall, M. D., Zygmunt, P. M., Movahed, P., & Högestätt, E. D. (2000). Vanilloid receptors on capsaicin-sensitive sensory nerves mediate relaxation to methanandamide in the rat isolated mesenteric arterial bed and small mesenteric arteries. British Journal of Pharmacology, 130(7), 1483-8.
Ralevic V, et al. Vanilloid Receptors On Capsaicin-sensitive Sensory Nerves Mediate Relaxation to Methanandamide in the Rat Isolated Mesenteric Arterial Bed and Small Mesenteric Arteries. Br J Pharmacol. 2000;130(7):1483-8. PubMed PMID: 10928948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vanilloid receptors on capsaicin-sensitive sensory nerves mediate relaxation to methanandamide in the rat isolated mesenteric arterial bed and small mesenteric arteries. AU - Ralevic,V, AU - Kendall,D A, AU - Randall,M D, AU - Zygmunt,P M, AU - Movahed,P, AU - Högestätt,E D, PY - 2000/8/6/pubmed PY - 2001/2/28/medline PY - 2000/8/6/entrez SP - 1483 EP - 8 JF - British journal of pharmacology JO - Br J Pharmacol VL - 130 IS - 7 N2 - In the present study, the vasodilator actions of methanandamide and capsaicin in the rat isolated mesenteric arterial bed and small mesenteric arterial segments were investigated. Methanandamide elicited concentration-dependent relaxations of preconstricted mesenteric arterial beds (pEC(50)=6.0+/-0.1, E(max)=87+/-3%) and arterial segments (pEC(50)=6.4+/-0.1, E(max)=93+/-3%). In arterial beds, in vitro capsaicin pre-treatment blocked vasorelaxation to 1 and 3 microM methanandamide, and reduced to 12+/-7% vasorelaxation to 10 microM methanandamide. Methanandamide failed to relax arterial segments pre-treated in vitro with capsaicin. In arterial beds from rats treated as neonates with capsaicin to cause destruction of primary afferent nerves, methanandamide at 1 and 3 microM did not evoke vasorelaxation, and relaxation at 10 microM methanandamide was reduced to 26+/-4%. Ruthenium red (0.1 microM), an inhibitor of vanilloid responses, attenuated vasorelaxation to methanandamide in arterial beds (pEC(50)=5.6+/-0.1, E(max)=89+/-1%). Ruthenium red at 1 microM abolished the response to 1 microM methanandamide, and greatly attenuated relaxation at 3 and 10 microM methanandamide in arterial beds. In arterial segments, ruthenium red (0.15 microM) blocked vasorelaxation to methanandamide, but not to CGRP. In arterial segments, the vanilloid receptor antagonist capsazepine (1 microM) inhibited, and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8 - 37) (3 microM) abolished, methanandamide-induced relaxations. CGRP(8 - 37), but not capsazepine, attenuated significantly relaxation to exogenous CGRP. These data show that capsaicin and ruthenium red attenuate vasorelaxation to methanandamide in the rat isolated mesenteric arterial bed and small mesenteric arterial segments. In addition, CGRP(8 - 37) and capsazepine antagonize responses to methanandamide in mesenteric arterial segments. In conclusion, vanilloid receptors on capsaicin-sensitive sensory nerves play an important role in the vasorelaxant action of methanandamide in the rat isolated mesenteric arterial bed and small mesenteric arterial segments. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/10928948/Vanilloid_receptors_on_capsaicin_sensitive_sensory_nerves_mediate_relaxation_to_methanandamide_in_the_rat_isolated_mesenteric_arterial_bed_and_small_mesenteric_arteries_ L2 - https://doi.org/10.1038/sj.bjp.0703456 DB - PRIME DP - Unbound Medicine ER -