title: Effects of short-term exposure to homocysteine on vascular responsiveness of human internal mammary artery.
abstract: The aim of this study was to investigate the acute direct effects of homocysteine (Hcy) on the vascular responsiveness of human internal mammary artery (IMA) and to define the possible underlying mechanisms. The contractile response to both phenylephrine (Phe) (-36%) and KCl (-18%) was significantly reduced in arteries that were incubated with Hcy (10 (-4)M, 30 minutes), compared with controls (P < 0.05). Removal of endothelium did not significantly alter the responses of human IMA to Phe. Hcy (10 (-6)M) also caused a relaxation response in human IMA rings precontracted with Phe (10 (-4) M) and this effect was not inhibited by N-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), by l-NAME (10 (-4)M) + indomethacin (10 (-4)M), or by intimal rubbing. In addition, contractions induced by stepwise addition to calcium (Ca2+) to high KCl solution with no Ca(2+) were significantly inhibited by Hcy incubation as well as contractions induced by Phe in the absence of extracellular Ca (2+) (P < 0.05). On the other hand, Hcy (10 M, 30 minutes) did not significantly inhibit the relaxation responses to either acetylcholine (ACh) or sodium nitroprusside (SNP) (P > 0.05). These results demonstrated that short-term exposure to Hcy significantly decreased vascular responsiveness in human IMA without affecting endothelium-dependent and -independent vasorelaxation. This effect is not NO-, prostaglandin- or endothelium-dependent. The mechanism is uncertain but seems to depend on the interactions of Hcy with Ca(2+) influxes and/or other undefined direct effects in this tissue.
authors.affiliation: Department of Pharmacology, Akdeniz University Medical Faculty, Antalya, Turkey. ardatas@akdeniz.edu.tr
authors.forename: Arda
authors.initials: A
authors.lastname: Tasatargil
authors.forename: Gulay
authors.initials: G
authors.lastname: Sadan
authors.forename: Ilhan
authors.initials: I
authors.lastname: Golbasi
authors.forename: Edibe
authors.initials: E
authors.lastname: Karasu
authors.forename: Cengiz
authors.initials: C
authors.lastname: Turkay
mesh_terms: D000368:Aged; D002118:Calcium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006710:Homocysteine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D006710:Homocysteine; D009599:Nitroprusside; D010656:Phenylephrine; D011189:Potassium Chloride; D002118:Calcium