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Effects of chronic nitric oxide synthase inhibition on the cardiovascular responses to cannabinoids in vivo and in vitro.
Br J Pharmacol. 2007 Mar; 150(5):662-71.BJ

Abstract

BACKGROUND AND PURPOSE

Since the vasorelaxant potency of the endocannabinoid anandamide is enhanced in perfused mesenteric vascular beds from rats made hypertensive by chronic inhibition of NO synthase (L-NAME in drinking water), we hypothesized that in vivo, anandamide-induced vasodilatation would be similarly enhanced in L-NAME-treated animals.

EXPERIMENTAL APPROACH

Male Sprague-Dawley rats were given L-NAME in drinking water (7.5 mg kg(-1) day(-1)) for 4 weeks. Relaxant effects of anandamide were measured in perfused mesenteric vascular beds and in isolated small mesenteric arteries. Renal, mesenteric and hindquarters haemodynamic responses to anandamide, methanandamide, the synthetic cannabinoid agonist WIN-55212-2 and the cannabinoid receptor antagonist AM251 were assessed in conscious, chronically-instrumented rats.

KEY RESULTS

Vasorelaxant responses to anandamide were enhanced in the perfused mesentery but not in isolated mesenteric resistance vessels. In vivo, anandamide caused vasodilatation only in the hindquarters vascular bed and only in control rats. Methanandamide caused a late-onset (40 min after administration) tachycardia, mesenteric and hindquarters vasoconstriction, and renal vasodilatation, which did not differ between control and L-NAME-treated rats. AM251 had no effect on resting blood pressure in control or L-NAME-treated rats and WIN55212-2 caused pressor and renal and mesenteric vasoconstrictor responses, with hindquarters vasodilatation in both groups of animals.

CONCLUSIONS AND IMPLICATIONS

The results provide no in vivo evidence for enhanced vasodilator responses to cannabinoids, or up-regulation of endocannabinoids or their receptor activity, following chronic NO synthase inhibition.

Authors+Show Affiliations

Centre for Integrated Systems Biology & Medicine, School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK.No 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

17245361

Citation

Wheal, A J., et al. "Effects of Chronic Nitric Oxide Synthase Inhibition On the Cardiovascular Responses to Cannabinoids in Vivo and in Vitro." British Journal of Pharmacology, vol. 150, no. 5, 2007, pp. 662-71.
Wheal AJ, Bennett T, Randall MD, et al. Effects of chronic nitric oxide synthase inhibition on the cardiovascular responses to cannabinoids in vivo and in vitro. Br J Pharmacol. 2007;150(5):662-71.
Wheal, A. J., Bennett, T., Randall, M. D., & Gardiner, S. M. (2007). Effects of chronic nitric oxide synthase inhibition on the cardiovascular responses to cannabinoids in vivo and in vitro. British Journal of Pharmacology, 150(5), 662-71.
Wheal AJ, et al. Effects of Chronic Nitric Oxide Synthase Inhibition On the Cardiovascular Responses to Cannabinoids in Vivo and in Vitro. Br J Pharmacol. 2007;150(5):662-71. PubMed PMID: 17245361.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of chronic nitric oxide synthase inhibition on the cardiovascular responses to cannabinoids in vivo and in vitro. AU - Wheal,A J, AU - Bennett,T, AU - Randall,M D, AU - Gardiner,S M, Y1 - 2007/01/22/ PY - 2007/1/25/pubmed PY - 2007/5/11/medline PY - 2007/1/25/entrez SP - 662 EP - 71 JF - British journal of pharmacology JO - Br J Pharmacol VL - 150 IS - 5 N2 - BACKGROUND AND PURPOSE: Since the vasorelaxant potency of the endocannabinoid anandamide is enhanced in perfused mesenteric vascular beds from rats made hypertensive by chronic inhibition of NO synthase (L-NAME in drinking water), we hypothesized that in vivo, anandamide-induced vasodilatation would be similarly enhanced in L-NAME-treated animals. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats were given L-NAME in drinking water (7.5 mg kg(-1) day(-1)) for 4 weeks. Relaxant effects of anandamide were measured in perfused mesenteric vascular beds and in isolated small mesenteric arteries. Renal, mesenteric and hindquarters haemodynamic responses to anandamide, methanandamide, the synthetic cannabinoid agonist WIN-55212-2 and the cannabinoid receptor antagonist AM251 were assessed in conscious, chronically-instrumented rats. KEY RESULTS: Vasorelaxant responses to anandamide were enhanced in the perfused mesentery but not in isolated mesenteric resistance vessels. In vivo, anandamide caused vasodilatation only in the hindquarters vascular bed and only in control rats. Methanandamide caused a late-onset (40 min after administration) tachycardia, mesenteric and hindquarters vasoconstriction, and renal vasodilatation, which did not differ between control and L-NAME-treated rats. AM251 had no effect on resting blood pressure in control or L-NAME-treated rats and WIN55212-2 caused pressor and renal and mesenteric vasoconstrictor responses, with hindquarters vasodilatation in both groups of animals. CONCLUSIONS AND IMPLICATIONS: The results provide no in vivo evidence for enhanced vasodilator responses to cannabinoids, or up-regulation of endocannabinoids or their receptor activity, following chronic NO synthase inhibition. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/17245361/Effects_of_chronic_nitric_oxide_synthase_inhibition_on_the_cardiovascular_responses_to_cannabinoids_in_vivo_and_in_vitro_ L2 - https://doi.org/10.1038/sj.bjp.0707136 DB - PRIME DP - Unbound Medicine ER -