Tags

Type your tag names separated by a space and hit enter

Identification of two distinct vasodilator pathways activated by ATP in the mesenteric bed of the rat.
Br J Pharmacol. 2001 Jul; 133(6):825-32.BJ

Abstract

Adenosine 5'-triphosphate (ATP) has important roles in the cardiovascular system, modulating vascular tone by acting as both a vasoconstrictor and a vasodilator. The dilator function of ATP is traditionally thought to be monophasic and mediated primarily by nitric oxide (NO). Here we have identified the endothelium-dependent biphasic nature of ATP-induced vasodilatation of the rat isolated mesenteric bed and investigated the two distinct pathways involved. ATP, at doses of 1x10(-11) to 1x10(-8) moles, induced transient relaxations that were inhibited by the NO synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME: 1x10(-4) M), the soluble guanylyl cyclase inhibitor, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ: 3x10(-6) M) and KCl (6x10(-2) - 1.2x10(-1) M). At doses upwards of 1x10(-8) moles (1x10(-8) - 3x10(-7) moles), ATP also induced prolonged vasodilatations which were unaltered by L-NAME, L-NAME (1x10(-3) M) and indomethacin (1x10(-5) M), or by ODQ, but were abolished in the presence of KCl. In addition, the cannabinoid CB(1) receptor antagonist SR141716A (1x10(-5) M) was found to inhibit the second prolonged phase of vasodilatation. However, at the concentration used SR141716A is reported to be non-selective. A second CB(1) receptor antagonist, AM251 (1x10(-6) M), had a small but significant inhibitory effect on the second phase of ATP-induced vasodilatation. SR141716A, AM251 and KCl (6x10(-2) - 1.2x10(-1) M) all inhibited anandamide-induced relaxation of the isolated mesenteric bed. These observations demonstrate that ATP stimulates vasodilatation of the mesenteric bed by two distinct mechanisms involving the release of NO and an EDHF. In the absence of better pharmacological tools we can only speculate as to the involvement of an endogenous CB(1) receptor ligand in these responses.

Authors+Show Affiliations

Unit of Critical Care, Imperial College School of Medicine, NHLI, Dovehouse Street, London, SW3 6LY.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11454655

Citation

Stanford, S J., et al. "Identification of Two Distinct Vasodilator Pathways Activated By ATP in the Mesenteric Bed of the Rat." British Journal of Pharmacology, vol. 133, no. 6, 2001, pp. 825-32.
Stanford SJ, Gitlin JM, Mitchell JA. Identification of two distinct vasodilator pathways activated by ATP in the mesenteric bed of the rat. Br J Pharmacol. 2001;133(6):825-32.
Stanford, S. J., Gitlin, J. M., & Mitchell, J. A. (2001). Identification of two distinct vasodilator pathways activated by ATP in the mesenteric bed of the rat. British Journal of Pharmacology, 133(6), 825-32.
Stanford SJ, Gitlin JM, Mitchell JA. Identification of Two Distinct Vasodilator Pathways Activated By ATP in the Mesenteric Bed of the Rat. Br J Pharmacol. 2001;133(6):825-32. PubMed PMID: 11454655.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of two distinct vasodilator pathways activated by ATP in the mesenteric bed of the rat. AU - Stanford,S J, AU - Gitlin,J M, AU - Mitchell,J A, PY - 2001/7/17/pubmed PY - 2001/9/8/medline PY - 2001/7/17/entrez SP - 825 EP - 32 JF - British journal of pharmacology JO - Br J Pharmacol VL - 133 IS - 6 N2 - Adenosine 5'-triphosphate (ATP) has important roles in the cardiovascular system, modulating vascular tone by acting as both a vasoconstrictor and a vasodilator. The dilator function of ATP is traditionally thought to be monophasic and mediated primarily by nitric oxide (NO). Here we have identified the endothelium-dependent biphasic nature of ATP-induced vasodilatation of the rat isolated mesenteric bed and investigated the two distinct pathways involved. ATP, at doses of 1x10(-11) to 1x10(-8) moles, induced transient relaxations that were inhibited by the NO synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME: 1x10(-4) M), the soluble guanylyl cyclase inhibitor, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ: 3x10(-6) M) and KCl (6x10(-2) - 1.2x10(-1) M). At doses upwards of 1x10(-8) moles (1x10(-8) - 3x10(-7) moles), ATP also induced prolonged vasodilatations which were unaltered by L-NAME, L-NAME (1x10(-3) M) and indomethacin (1x10(-5) M), or by ODQ, but were abolished in the presence of KCl. In addition, the cannabinoid CB(1) receptor antagonist SR141716A (1x10(-5) M) was found to inhibit the second prolonged phase of vasodilatation. However, at the concentration used SR141716A is reported to be non-selective. A second CB(1) receptor antagonist, AM251 (1x10(-6) M), had a small but significant inhibitory effect on the second phase of ATP-induced vasodilatation. SR141716A, AM251 and KCl (6x10(-2) - 1.2x10(-1) M) all inhibited anandamide-induced relaxation of the isolated mesenteric bed. These observations demonstrate that ATP stimulates vasodilatation of the mesenteric bed by two distinct mechanisms involving the release of NO and an EDHF. In the absence of better pharmacological tools we can only speculate as to the involvement of an endogenous CB(1) receptor ligand in these responses. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/11454655/Identification_of_two_distinct_vasodilator_pathways_activated_by_ATP_in_the_mesenteric_bed_of_the_rat_ L2 - https://doi.org/10.1038/sj.bjp.0704139 DB - PRIME DP - Unbound Medicine ER -