Time course and extent of recovery of endothelium-dependent contractions and relaxations after direct arterial injury.
To determine the time course of the return of endothelium-dependent relaxations and contractions during intimal regeneration, we performed balloon endothelial denudation of the thoracic and abdominal aorta of male Lewis rats and examined smooth muscle function and endothelium-dependent responses in vitro at 1, 2, 4, and 8 weeks after aortic injury. At each study interval during endothelial cell regeneration, vascular smooth muscle contracted and relaxed normally to direct stimulation with norepinephrine and sodium nitroprusside. Endothelium-dependent contractions to serotonin returned to normal at 1 week and developed into a hypercontractile response at 8 weeks. Endothelium-dependent relaxations to acetylcholine returned to normal at 8 weeks, but endothelium-dependent relaxations to adenosine diphosphate remained impaired. These experiments demonstrate that regenerating endothelium regains the ability to produce contracting factor before relaxing factor, and it even exhibits potentiated contractile activity 8 weeks after injury. Thus, after direct arterial injury, regenerating endothelium has abnormal endothelium-dependent function that predisposes the vessel to vasospasm and thrombosis.
Cartier
R
R
Division of Thoracic and Cardiovascular Surgery, Mayo Clinic, Rochester, Minn 55905.
Pearson
P J
PJ
Lin
P J
PJ
Schaff
H V
HV
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000293:injuries / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D012701:Serotonin / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D012701:Serotonin; D000244:Adenosine Diphosphate; D000109:Acetylcholine; D009638:Norepinephrine