Flow-induced constriction in arterioles of hyperhomocysteinemic rats is due to impaired nitric oxide and enhanced thromboxane A2 mediation

Zsolt Bagi, Zoltan Ungvari, Lajos Szollár, Akos Koller

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Hyperhomocysteinemia (HHcy) is thought to promote arteriosclerosis and peripheral arterial disease, in part by impairing the function of endothelium. Because flow-induced dilation is mediated by the endothelium, we hypothesized that HHcy alters this response by interfering with the synthesis/action of NO and prostaglandins. Thus, changes in the diameter of isolated, pressurized (at 80 mm Hg) gracilis skeletal muscle arterioles (diameter ≈ 170/μm) from control and methionine diet-induced HHcy rats were investigated with videomicroscopy. Increases in intraluminal flow (from 0 to 25 μL/min) resulted in dilations of control arterioles (maximum, 34±4 μm). In contrast, increases in flow elicited constrictions of HHcy arterioles (-36±3 μm). In control arterioles, the NO synthase inhibitor Nω-nitro-L-argininemethyl ester significantly attenuated (≈50%) dilation, whereas the additional administration of indomethacin, an inhibitor of cyclooxygenase, eliminated flow-induced dilation. In the arterioles of HHcy rats, flow-induced constriction was not affected by Nωnitro-L-arginine-methyl ester, whereas it was abolished by indomethacin or the prostaglandin H2/thromboxane A2 (TXA2) receptor antagonist SQ 29,548 or the TXA2 synthase inhibitor CGS 13,080. Thus, in HHcy, increases in intraluminal flow elicit constrictions of skeletal muscle arterioles due to the impaired NO and enhanced TXA2 mediation of the response, alterations that likely contribute to the development of peripheral arterial disease.

Original languageEnglish (US)
Pages (from-to)233-237
Number of pages5
JournalArteriosclerosis, thrombosis, and vascular biology
Volume21
Issue number2
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Fingerprint

Hyperhomocysteinemia
Thromboxane A2
Arterioles
Constriction
Nitric Oxide
Dilatation
Peripheral Arterial Disease
Indomethacin
Endothelium
Skeletal Muscle
Prostaglandin H2 Receptors Thromboxane A2
Video Microscopy
Cyclooxygenase Inhibitors
Arteriosclerosis
Nitric Oxide Synthase
Methionine
Prostaglandins
Esters
Diet

Keywords

  • Arteriole
  • Endothelium
  • Flow-induced response
  • Homocysteine
  • Nitric oxide
  • Thromboxane A

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Flow-induced constriction in arterioles of hyperhomocysteinemic rats is due to impaired nitric oxide and enhanced thromboxane A2 mediation. / Bagi, Zsolt; Ungvari, Zoltan; Szollár, Lajos; Koller, Akos.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 21, No. 2, 01.01.2001, p. 233-237.

Research output: Contribution to journalArticle

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