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1 Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, United States
* To whom correspondence should be addressed. E-mail: davidku{at}uab.edu.
We recently reported that coronary endothelial(CEC) dysfunction may contribute to the development of right ventricular hypertrophy(RVH) in monocrotaline(MCT) -induced pulmonary hypertensive rats. Present study investigated whether preservation of CEC function with garlic and its active metabolite allicin could abrogate RVH. Rats were fed with 1% raw garlic (RG) supplemented diet 1 day or 3 weeks before and 1 day after MCT injection and changes in RV pressure (RVP), RVH and CEC function were assessed 3 weeks after MCT administration. In all cases, RG feeding significantly inhibited the development of RVP and RVH in these MCT rats. However, similar treatments with either boiled garlic (BG) or aged garlic (AG), which do not contain the active allicin metabolite, were ineffective. CEC function, assessed with acetylcholine-induced dilation as well as L-NAME induced constriction, revealed marked attenuation in right, but not left, coronary arteries of the MCT rats. This is consistent with our earlier report. Feeding of RG, but not BG nor AG, preserved the CEC function and prevented the exaggerated vasoconstrictory responses of the MCT coronary arteries. There was no change in the coronary dilatory responses to a nitric oxide donor sodium nitroprusside. Further testings of vasoactivity to garlic extracts showed that only RG, but not BG nor AG, elicited a potent, dose-dependent dilation on the isolated coronaries. Taken together, these findings show that garlic protective effect against the development of RVP and RVH in monocrotaline-treated rats is probably mediated via its active metabolite allicin action on coronary endothelial function and vasoreactivity.
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