Effect of <i>L</i>-Carnitine and Propionyl-<i>L</i>-Carnitine on Endothelial Function of Small Mesenteric Arteries from SHR

Abstract

Background:The effect of treatment with either 200 mg·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.

Hypertension increases middle cerebral artery resting tone in spontaneously hypertensive rats: role of tonic vasoactive factor availability

“…The decrease in the presence of O 2 − in SHRs appears to be specific to the cerebral vasculature as, in third-order MRAs from age-matched rats, basal O 2 − was increased in SHRs instead. These findings are in accordance with several other studies performed in both conduit [40,41] and resistance [42] arteries from this strain.…”

L-Carnitine Ameliorates Glycerol-Induced Myoglobinuric Acute Renal Failure in Rats

“…Recently, it has been reported that L-carnitine was able to improve the endothelium-dependent relaxation of small mesenteric arteries from SHR by decreasing vascular O 2 − production, thus increasing NO participation in endothelial function. [26] These findings indicate that vasodilatation and the enhancement of renal perfusion contributed, at least in part, Data shown above are the mean ± SD. All parameters were determined in the rats that were killed at 96 hours.…”

Liver growth factor treatment restores cell-extracellular matrix balance in resistance arteries and improves left ventricular hypertrophy in SHR

“…Under our experimental conditions, MRA from SHR exhibited a biphasic response to ACh, whereas in WKY only a vasodilator component was observed. The contractile component was maintained after NO and EDHF blockade and has been previously demonstrated to be due to the effect of cyclooxygenase (COX)-derived prostanoids and/or free radicals released at high concentrations of ACh in SHR MRA, which are not produced in the WKY strain (2,30,69).…”

“…However, the present and previous data let us suggest that it can be linked to an antioxidant effect. First, LGF was able to reduce the elevated superoxide anion levels in SHR MRA, which is a common feature in several vascular beds from SHR (2,34). We have previously demonstrated that LGF exerts potent in vitro scavenging capacity against several ROS, including superoxide anion and hydroxyl and peroxyl radicals (18).…”

“…Resistance artery narrowing, increased stiffness, and reduced vasodilator responses are found in patients with essential hypertension (1,48,55) as well as in rat models of the disease such as the SHR and the stroke-prone rats (2,8,13,39). These alterations are not only important for the progression of hypertension but are also predictors of cardiovascular events in hypertensive subjects (48,55).…”