| Title | The in vitro and in vivo cardiovascular effects of {Delta}9-tetrahydrocannabinol (THC) in rats made hypertensive by chronic inhibition of nitric oxide synthase. | | Author(s) | O'sullivan SE, Randall MD, Gardiner SM | | Institution | University of Nottingham. | | Source | J Pharmacol Exp Ther 2007 Feb 6. | | Abstract | Evidence suggests that Delta(9)- tetrahydrocannabinol (THC) may have anti-hypertensive effects and that the vasodilator effect of endocannabinoids is enhanced in rats made hypertensive by chronic NO synthase inhibition. The aims of the present study were therefore to investigate whether the in vitro and in vivo cardiovascular responses to THC are altered by L-NAME treatment. The vasorelaxant effects of THC were enhanced in small mesenteric arteries from L-NAME-treated rats. This enhanced response was not inhibited by CB1 receptor antagonism (AM251, 1 microM). Pre-treating vessels with the TRPV1 receptor agonist, capsaicin (10 microM, 1 h), reduced vasorelaxation to THC to a greater extent in L-NAME-treated than control rats. Inhibition of cyclooxygenase with indomethacin (10 microM) inhibited THC responses in arteries from L-NAME-treated, but not control rats. In conscious, chronically-instrumented rats, THC (1 mg kg(-1) i.v.) caused a pressor effect, with vasoconstriction of the renal and mesenteric vascular beds, and hindquarters vasodilatation. Pre-treatment with AM251 (3 mg kg(-1) i.v.) reduced the pressor and vasoconstrictor effects of THC, abolished the hindquarters vasodilatation and revealed a bradycardic response. L-NAME-treated rats showed similar pressor and vasoconstrictor responses to THC, but with bradycardia, and reduced hindquarter vasodilatation. These data show that, in vitro, isolated arteries of L-NAME-treated rats show enhanced vasorelaxant responses to THC through an increased sensory nerve component and stimulation of prostanoids. However, in vivo, THC causes a CB1 receptor-mediated pressor effect with hindquarters vascular vasodilatation. There was no evidence of enhanced vasodilator effects of THC in L-NAME- treated animals in vivo. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 17284670 |
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