Asiatic acid reduces blood pressure by enhancing nitric oxide bioavailability with modulation of eNOS and p47phox expression in L-NAME-induced hypertensive rats.
We investigated the effect of asiatic acid (AA) on hemodynamic status, vascular function, oxidative stress markers, endothelial nitric oxide synthase (eNOS), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit expression in Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats treated with L-NAME (40 mg/kg/day) in drinking water for 5 weeks showed significant increases in mean arterial pressure, heart rate, hindlimb vascular resistance, vascular dysfunction, superoxide anion (O2(•-)) production, and plasma malondialdehyde. Moreover, NO metabolite (NOx) levels were reduced, aortic eNOS expression was downregulated, and NADPH oxidase subunit p47(phox) was upregulated in hypertensive rats (p < 0.05). Hypertensive rats that were administered AA (10 or 20 mg/kg/day) for the last 2 weeks of the study showed significant improvement in hemodynamic status and vascular function. The antihypertensive effects of AA were associated with elevated plasma NOx levels, together with upregulation of eNOS expression. Decreased vascular O2(•-) production, consistent with downregulation of p47(phox) expression, was also observed after AA treatment. Our results are therefore consistent with a model whereby AA reduces blood pressure by enhancing NO bioavailability.
Department of Physiology, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand.
Sarawoot
S
Bunbupha
Poungrat
P
Pakdeechote
Upa
U
Kukongviriyapan
Parichat
P
Prachaney
Veerapol
V
Kukongviriyapan
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D019255:NADPH Oxidases / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D000959:Antihypertensive Agents; D053978:Pentacyclic Triterpenes; D013481:Superoxides; D009569:Nitric Oxide; D008315:Malondialdehyde; C017032:asiatic acid; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D019331:NG-Nitroarginine Methyl Ester
asiatic acid; hypertension; nitric oxide; oxidative stress; vascular dysfunction