Journal Article

Vascular Endothelium-Dependent and Independent Actions of Oleanolic Acid and Its Synthetic Oleanane Derivatives as Possible Mechanisms for Hypotensive Effects

van Heerden, Fanie R., Dessy, Chantal, Metzinger, Thomas, Mubagwa, Kanigula, Madlala, Hlengiwe P., Musabayane, Cephas T.

2016

Overview

Plant-derived oleanolic acid (OA) and its related synthetic derivatives (Br-OA and Me-OA) possess antihypertensive effects in experimental animals. The present study investigated possible underlying mechanisms in rat isolated single ventricular myocytes and in vascular smooth muscles superfused at 37°C. Cell shortening was assessed at 1 Hz using a video-based edge-detection system and the L-type Ca2+ current (ICaL) was measured using the whole-cell patch-clamp technique in single ventricular myocytes. Isometric tension was measured using force transducer in isolated aortic rings and in mesenteric arteries. Vascular effects were measured in endothelium-intact and denuded vessels in the presence of various enzyme or channel inhibitors. OA and its derivatives increased cell shortening in cardiomyocytes isolated from normotensive rats but had no effect in those isolated from hypertensive animals. These triterpenes also caused relaxation in aortic rings and in mesenteric arteries pre-contracted with either phenylephrine or KCl-enriched solution. The relaxation was only partially inhibited by endothelium denudation, and also partly inhibited by the cyclooxygenase (COX) inhibitor indomethacin, with no additional inhibitory effect of the NO synthase inhibitor, N-ω-Nitro-L-arginine. A combination of both ATP-dependent channel inhibition by glibenclaminde and voltage-dependent K+ channel inhibition by 4-aminopyridine was necessary to fully inhibit the relaxation. These data indicate that the effects of OA and its derivatives are mediated via both endothelium-dependent and independent mechanisms suggesting the involvement of COX in the endothelium-dependent effects and of vascular muscle K+ channels in the endothelium-independent effects. Finally, our results support the view that the antihypertensive action of OA and its derivatives is due to a decrease of vascular resistance with no negative inotropic effect on the heart.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acids / Animals / Antihypertensive Agents - pharmacology / Antihypertensives / Aorta / Arginine / Arteries / Biology and Life Sciences / Blood vessels / Calcium channels (L-type) / Calcium ions / Cardiomyocytes / Care and treatment / Coronary vessels / Denudation / Derivatives / Development and progression / Endothelium / Endothelium, Vascular - drug effects / Enzymes / Health sciences / Heart / Hypertension / Hypertension - drug therapy / Hypotension - chemically induced / Indomethacin / Indomethacin - pharmacology / Inhibition / Inhibitors / Kinases / Laboratories / Male / Medicine and Health Sciences / Muscle Cells - drug effects / Muscle contraction / Muscle, Smooth, Vascular - drug effects / Muscles / Myocytes / Nitric-oxide synthase / Nitroarginine - pharmacology / Nutrition / Oleanolic acid / Oleanolic Acid - analogs & derivatives / Oleanolic Acid - pharmacology / Patient outcomes / Pharmacology / Phenylephrine / Phenylephrine - pharmacology / Phosphorylation / Physical Sciences / Plants / Potassium channels (voltage-gated) / Potassium Channels - drug effects / Potassium Channels - physiology / Potassium chloride / Potassium Chloride - pharmacology / Prostaglandin endoperoxide synthase / Prostaglandin-Endoperoxide Synthases - drug effects / Prostaglandin-Endoperoxide Synthases - physiology / Rats / Rats, Inbred Dahl / Rats, Wistar / Research and Analysis Methods / Rodents / Smooth muscle / Syzygium aromaticum / Triterpenes / Ventricle