The aporphine alkaloid boldine improves endothelial function in spontaneously hypertensive rats

Lau, Yeh-Siang; Machha, A.; Achike, F.I.; Mustafa, M.R.; Murugan, D. (2011) The aporphine alkaloid boldine improves endothelial function in spontaneously hypertensive rats. Experimental Biology and Medicine. ISSN 1535-3702

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    Abstract

    Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimentalrole in the pathogenesis of endothelial dysfunction in hypertension. In the present study, we investigated the effects of boldine on endothelial dysfunction in hypertension using spontaneously hypertensive rats (SHR), the most studied animal model of hypertension. SHR and their age-matched normotensive Wistar-Kyoto (WKY) rats were treated with boldine (20 mg/kg perday) or its vehicle, which served as control, for seven days. Control SHR displayed higher systolic blood pressure (SBP), reduced endothelium-dependent aortic relaxation to acetylcholine (ACh), marginally attenuated endothelium-independent aortic relaxation to sodium nitroprusside (SNP), increased aortic superoxide and peroxynitrite production, and enhanced p47 phox protein expression as compared with control WKY rats. Boldine treatment significantly lowered SBP in SHR but not in WKY. Boldine treatment enhanced the maximal relaxation to ACh in SHR, but had no effect in WKY, whereas the sensitivity to ACh was increased in both SHR and WKY aortas. Boldine treatment enhanced sensitivity, but was without effect on maximal aortic relaxation responses, to SNP in both WKY and SHR aortas. In addition, boldine treatment lowered aortic superoxide and peroxynitrite production and downregulated p47 phox protein expression in SHR aortas, but had no effect in the WKY control. These results show that boldine treatment exerts endothelial protective effects in hypertension, achieved, at least in part, through the inhibition of NADPH-mediated superoxide production.

    Item Type: Article
    Creators:
    1. Lau, Yeh-Siang
    2. Machha, A.
    3. Achike, F.I.
    4. Mustafa, M.R.
    5. Murugan, D.
    Journal or Publication Title: Experimental Biology and Medicine
    Additional Information: Department of Pharmacology, Faculty of Medicine, Centre of Natural Products and Drug Discovery (CENAR), University of Malaya,Kuala Lumpur 50603, Malaysia
    Uncontrolled Keywords: Boldine; Blood Pressure; Endothelial Function; Hypertension; Oxidative Stress
    Subjects: R Medicine
    R Medicine > RM Therapeutics. Pharmacology
    Divisions: Faculty of Medicine
    Depositing User: Ms Haslinda Lahuddin
    Date Deposited: 12 Jan 2012 09:17
    Last Modified: 12 Jan 2012 09:17
    URI: http://eprints.um.edu.my/id/eprint/2413

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