Vascular Effects of P2 Receptors. Changes in Congestive Heart Failure.

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Extracellular nucleotides induce dilatation and constriction of blood vessels by activation of P2 receptors. In this thesis the vasomotor effects of P2 receptor activation were studied in the rat mesenteric artery, and their changes in congestive heart failure (CHF) were evaluated using in vitro pharmacology, electrophysiology and competitive RT-PCR. Vasodilatation was induced by activation of P2Y1 and P2Y2 / P2Y4 receptors situated on the endothelium, while vasoconstriction was elicited most potently by P2Y6 and P2Y2 / P2Y4 receptors on smooth muscle cells, with a minor contribution by P2X1 receptors. Endothelial P2 receptors have so far been known to induce the release of nitric oxide and prostaglandins. Endothelium-derived hyperpolarising factor (EDHF) is also involved since its relaxing and hyperpolarising effects were abolished by a combination of charybdotoxin and apamin. The dilatory response to EDHF was more prominent in peripheral arteries. P2X receptors on smooth muscle cells functionally counteracted the dilatory and hyperpolarising effects of EDHF when stimulated by the same nucleotides. In experimental CHF there was a decreased NO release, indicating endothelium dysfunction. The EDHF dilatation was increased, while the contractile P2X1 receptor effects were downregulated in a compensatory manner. These findings suggest important regulatory mechanisms in the aim to maintain peripheral tissue perfusion during CHF.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Other Clinical Medicine

Keywords

  • congestive heart failure, pyrimidine, purine, P2 receptor, vasodilatation, vasoconstriction, hyperpolarisation, EDHF, NO, Vascular, endothelium, Cardiovascular system, Kardiovaskulära systemet
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date2001 Jan 13
Publisher
  • Malin Malmsjö, Experimental Vascular Research, Wallenberg Neuroscience center 3rd floor, Sölveg. 17, 22184 Lund,
Publication statusPublished - 2001
Publication categoryResearch

Bibliographic note

Defence details Date: 2001-01-13 Time: 10:30 Place: Lund External reviewer(s) Name: Bryan, Robert Title: Prof Affiliation: [unknown] ---