Boldine, a major
aporphine alkaloid found in Chilean boldo tree, is a potent
antioxidant. Oxidative stress plays a detrimental role 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 per day) 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.