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Unusual absence of endothelium-dependent or -independent vasodilatation to purines or pyrimidines in the rat renal artery.
Kidney Int 2003; 64(4):1389-97KI

Abstract

BACKGROUND

Adenosine triphosphate (ATP) is a cotransmitter with noradrenaline (NA) in sympathetic perivascular nerves. It has a dual role in the maintenance of vascular tone as ATP, released from endothelial cells during shear stress or hypoxia, induces vasodilatation via endothelial P2Y receptors or by direct action on smooth muscle. The role and distribution of P2 receptors is well characterized for many blood vessels but not for the rat renal artery. This study aims to determine whether ATP is a vasoconstrictor cotransmitter with NA and whether ATP induces vasodilatation via the endothelium or smooth muscle.

METHODS

On isolated rat renal arteries, electrical field stimulation (EFS) in the absence and presence of antagonists to P2X receptors and alpha1-adrenoceptors was examined. Concentration-response curves were constructed to NA, ATP, alpha,beta-methylene ATP (alpha,beta-meATP), uridine triphosphate (UTP), and 2-methylthio ADP (2-MeSADP) on low tone. Curves to acetylcholine (ACh), 2-MeSADP, and UTP were constructed on raised tone. Immunofluorescent localization of P2X and P2Y receptor subtypes was performed.

RESULTS

Electrical field stimulation induced vasoconstriction, partially inhibited by the P2X receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, and predominantly by prazosin. Exogenous NA and ATP mimicked EFS; immunostaining for P2X1 and P2X2 receptors was expressed on vascular smooth muscle. Unusually, ATP, 2-MeSADP, and UTP failed to induce vasodilatation. Acetylcholine induced vasodilatation. alpha,beta-meATP, 2-MeSADP, and UTP induced vasoconstriction via P2X1, P2Y1, and P2Y2 receptors, respectively. Immunostaining for P2X1, P2Y1, and P2Y2 receptors was expressed on the vascular smooth muscle.

CONCLUSION

Adenosine triphosphate and NA are cotransmitters in sympathetic nerves supplying the rat renal artery, NA being the dominant partner. The novel feature of this vessel is that purines and pyrimidines do not produce either endothelium-dependent or -independent vasodilatation; P2X1, P2Y1, and P2Y2 receptors on the smooth muscle all mediate vasoconstriction.

Authors+Show Affiliations

Autonomic Neuroscience Institute, Royal Free and University College Medical School, London.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12969158

Citation

Knight, Gillian E., et al. "Unusual Absence of Endothelium-dependent or -independent Vasodilatation to Purines or Pyrimidines in the Rat Renal Artery." Kidney International, vol. 64, no. 4, 2003, pp. 1389-97.
Knight GE, Oliver-Redgate R, Burnstock G. Unusual absence of endothelium-dependent or -independent vasodilatation to purines or pyrimidines in the rat renal artery. Kidney Int. 2003;64(4):1389-97.
Knight, G. E., Oliver-Redgate, R., & Burnstock, G. (2003). Unusual absence of endothelium-dependent or -independent vasodilatation to purines or pyrimidines in the rat renal artery. Kidney International, 64(4), pp. 1389-97.
Knight GE, Oliver-Redgate R, Burnstock G. Unusual Absence of Endothelium-dependent or -independent Vasodilatation to Purines or Pyrimidines in the Rat Renal Artery. Kidney Int. 2003;64(4):1389-97. PubMed PMID: 12969158.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Unusual absence of endothelium-dependent or -independent vasodilatation to purines or pyrimidines in the rat renal artery. AU - Knight,Gillian E, AU - Oliver-Redgate,Rachel, AU - Burnstock,Geoffrey, PY - 2003/9/13/pubmed PY - 2004/5/29/medline PY - 2003/9/13/entrez SP - 1389 EP - 97 JF - Kidney international JO - Kidney Int. VL - 64 IS - 4 N2 - BACKGROUND: Adenosine triphosphate (ATP) is a cotransmitter with noradrenaline (NA) in sympathetic perivascular nerves. It has a dual role in the maintenance of vascular tone as ATP, released from endothelial cells during shear stress or hypoxia, induces vasodilatation via endothelial P2Y receptors or by direct action on smooth muscle. The role and distribution of P2 receptors is well characterized for many blood vessels but not for the rat renal artery. This study aims to determine whether ATP is a vasoconstrictor cotransmitter with NA and whether ATP induces vasodilatation via the endothelium or smooth muscle. METHODS: On isolated rat renal arteries, electrical field stimulation (EFS) in the absence and presence of antagonists to P2X receptors and alpha1-adrenoceptors was examined. Concentration-response curves were constructed to NA, ATP, alpha,beta-methylene ATP (alpha,beta-meATP), uridine triphosphate (UTP), and 2-methylthio ADP (2-MeSADP) on low tone. Curves to acetylcholine (ACh), 2-MeSADP, and UTP were constructed on raised tone. Immunofluorescent localization of P2X and P2Y receptor subtypes was performed. RESULTS: Electrical field stimulation induced vasoconstriction, partially inhibited by the P2X receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, and predominantly by prazosin. Exogenous NA and ATP mimicked EFS; immunostaining for P2X1 and P2X2 receptors was expressed on vascular smooth muscle. Unusually, ATP, 2-MeSADP, and UTP failed to induce vasodilatation. Acetylcholine induced vasodilatation. alpha,beta-meATP, 2-MeSADP, and UTP induced vasoconstriction via P2X1, P2Y1, and P2Y2 receptors, respectively. Immunostaining for P2X1, P2Y1, and P2Y2 receptors was expressed on the vascular smooth muscle. CONCLUSION: Adenosine triphosphate and NA are cotransmitters in sympathetic nerves supplying the rat renal artery, NA being the dominant partner. The novel feature of this vessel is that purines and pyrimidines do not produce either endothelium-dependent or -independent vasodilatation; P2X1, P2Y1, and P2Y2 receptors on the smooth muscle all mediate vasoconstriction. SN - 0085-2538 UR - https://www.unboundmedicine.com/medline/citation/12969158/Unusual_absence_of_endothelium_dependent_or__independent_vasodilatation_to_purines_or_pyrimidines_in_the_rat_renal_artery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(15)49476-1 DB - PRIME DP - Unbound Medicine ER -