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Professor Malin Malmsjö, MD, PhD. Photo.

Malin Malmsjö

Professor

Professor Malin Malmsjö, MD, PhD. Photo.

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

Author

  • Malin Malmsjö

Summary, in English

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.

Department/s

  • Medicine, Lund

Publishing year

2001

Language

English

Document type

Dissertation

Publisher

Malin Malmsjö, Experimental Vascular Research, Wallenberg Neuroscience center 3rd floor, Sölveg. 17, 22184 Lund,

Topic

  • Other Clinical Medicine

Keywords

  • congestive heart failure
  • pyrimidine
  • purine
  • P2 receptor
  • vasodilatation
  • vasoconstriction
  • hyperpolarisation
  • EDHF
  • NO
  • Vascular
  • endothelium
  • Cardiovascular system
  • Kardiovaskulära systemet

Status

Published

Supervisor

  • [unknown] [unknown]

ISBN/ISSN/Other

  • ISRN LUMEDW/MEMA-2001(1065)-SE

Defence date

13 January 2001

Defence time

10:30

Defence place

Lund

Opponent

  • Robert Bryan (Prof)