l-carnitine and its propionate: improvement of endothelial function in SHR through superoxide dismutase-dependent mechanisms.
To clarify the mechanism underlying the antioxidant properties of l-carnitine (LC) and propionyl-l-carnitine (PLC) on spontaneously hypertensive (SHR) and normotensive WKY, animals were treated with either PLC or LC (200 mg kg(- 1)). Aorta was dissected and contraction to (R)-( - )-phenylephrine (Phe) and relaxation to carbachol (CCh) were assessed in the presence or not of the NO synthase (NOS) inhibitor, l-NAME. [image omitted] production was evaluated by lucigenin-enhanced chemiluminescence and its participation on relaxation was observed after incubation with superoxide dismutase (SOD) plus catalase. Protein expressions of eNOS, Cu/Zn-SOD and Mn-SOD were studied by western blot. Both LC and PLC treatments improved endothelial function of SHR through increasing NO participation and decreasing [image omitted] probably involving higher Cu/Zn-SOD expression. PLC treatment augmented eNOS expression in SHR. Surprisingly, LC increased [image omitted] produced by aorta from WKY and thus diminished NO and damaged endothelial function. Conversely, PLC did not affect CCh-induced relaxation in WKY. These results demonstrate that LC and PLC prevent endothelial dysfunction in SHR through an antioxidant effect.
de Sotomayor
Maria Alvarez
MA
Departamento de Farmacologia, Facultad de Farmacia, Universidad de Sevilla, Seville, Spain. aldesoto@us.es
Mingorance
Carmen
C
Rodriguez-Rodriguez
Rosalía
R
Marhuenda
Elisa
E
Herrera
Maria Dolores
MD
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D013481:Superoxides; C003223:propionylcarnitine; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D002331:Carnitine; D019331:NG-Nitroarginine Methyl Ester