N,N-diacetyl-L-cystine improves endothelial function in atherosclerotic Watanabe heritable hyperlipidaemic rabbits.
N,N-diacetyl-L-cystine (DiNAC), a novel immunomodulator, stimulates contact sensitivity/delayed type hypersensitivity reactions in mice induced by oxazolone and reduces atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL) rabbits. Forty-week-old WHHL rabbits were given DiNAC (3 micromol/kg per day) for 8 weeks, and endothelium-mediated dilatation was investigated in vivo using pulse wave analysis. A significant improvement in endothelial function was found after 3 weeks of treatment, which was further improved after 8 weeks. For experiments on isolated blood vessels, 40-week-old rabbits were treated for 3 weeks. Treatment did not affect plasma lipid levels. At termination, aortic rings from the thoracic and abdominal aorta were contracted with phenylephrine in vitro. Concentration-effect curves to acetylcholine and the calcium ionophore A 23187 were used to measure endothelium-mediated vasodilatation, and nitroprusside to elicit endothelium-independent relaxations. Abdominal aorta relaxations were generally larger than in thoracic aorta. DiNAC improved endothelium-dependent relaxations in the abdominal but not in the thoracic aorta. This effect was independent of the degree of atherosclerosis. It is concluded that DiNAC improved endothelial function in atherosclerotic rabbit arteries in vivo and in vitro, and may represent a new treatment modality for atherosclerosis-related diseases.
Pettersson
Knut S
KS
AstraZeneca R&D Mölndal, Mölndal, Sweden.
Eliasson
Ulla Brandt
UB
Abrahamsson
Tommy
T
Wågberg
Maria
M
Carrier
Martin
M
Kengatharan
Ken M
KM
D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D050197:Atherosclerosis / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D003553:Cystine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D007155:Immunologic Factors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011673:Pulsatile Flow / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014881:Water Supply
D007155:Immunologic Factors; D003553:Cystine; C056709:N,N-diacetylcystine; D000109:Acetylcholine