Effect of L-carnitine and propionyl-L-carnitine on endothelial function of small mesenteric arteries from SHR.
BACKGROUND
The effect of treatment with either 200 mg x kg(-1) of L-carnitine (LC) or propionyl-L-carnitine (PLC) was studied on endothelial dysfunction of small mesenteric arteries (SMA) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats.


METHODS
Systolic blood pressure (SBP) was measured and endothelial and vascular functions were assessed by the effect of carbachol (CCh) and phenylephrine (Phe). O2- produced by SMA and eNOS expression were evaluated by chemiluminescence and Western blot, respectively.


RESULTS
Although SBP was not affected, endothelial relaxation increased in both LC- and PLC-treated SHR. Nevertheless, the CCh-induced contraction remained sensitive to indomethacin in these rats. On the contrary, NO participation was increased in all the groups except for LC-treated WKY. Furthermore, high concentrations of Phe produced NO-dependent relaxation of SMA from PLC-treated rats. Both compounds decreased basal and NADPH-stimulated O2- in SHR toward values observed in WKY. Only PLC increased eNOS protein expression in SHR. Neither LC nor PLC affected endothelium-derived hyperpolarizing factor-induced relaxation.


CONCLUSIONS
LC and its propionate improved endothelial responses of SMA from SHR by decreasing O2- production and thus increasing NO availability. PLC also increased NO synthesis by enhancing eNOS expression.
Alvarez de Sotomayor
Maria
M
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain. aldesoto@us.es
Bueno
Rosario
R
Pérez-Guerrero
Concepción
C
Herrera
Maria Dolores
MD
D000818:Animals; D001685:Biological Factors / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000473:pathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects*; D018721:Muscarinic Agonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000493:pharmacokinetics*
D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D018721:Muscarinic Agonists; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D013481:Superoxides; C003223:propionylcarnitine; D010656:Phenylephrine; D009569:Nitric Oxide; D002217:Carbachol; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D002331:Carnitine; D007213:Indomethacin