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1 Pharmacology & Physiology, UMDNJ-New Jersey Medical School, Newark, New Jersey, United States
2 Newark, New Jersey, United States; Pharmacology & Physiology, UMDNJ-New Jersey Medical School, Newark, New Jersey, United States
3 Pharmacology and Physiology, MSB H-609, New Jersey Medical School, Newark, New Jersey, United States
* To whom correspondence should be addressed. E-mail: kimda{at}umdnj.edu.
Danshen, a Chinese herb, reduces hypertension in Oriental Medicine. We hypothesized that Danshen acts partially through endothelial nitric oxide synthase (eNOS) signaling mechanisms. We tested the hypothesis using tanshinone IIA, an active ingredient of Danshen, and the 2-kidney-1-clip renovascular (2K1C) hypertension model in hamsters. Oral tanshinone (50 µg/100g of body weight) reduced mean arterial pressure (MAP) from 161.2±6.9 to 130.0±7.8 mmHg (mean±SEM; p<0.05) in hypertensive hamsters. MAP in sham-operated hamsters was 114.3±9.2 mmHg. Topical tanshinone at 1 µg/ml and 5 µg/ml increased normalized arteriolar diameter from 1.00 to 1.25±0.08 and 1.57±0.11, and increased periarteriolar nitric oxide concentration from 87.1±11.3 nM to 146.9±23.1 nM (p<0.05) at 5 µg/ml in hamster cheek pouch. NG-monomethyl-L-arginine inhibited tanshinone-induced vasodilatation. Hypertension reduced eNOS protein relative to sham-operated control. Tanshinone prevented the hypertension-induced reduction of eNOS, and increased eNOS expression to levels higher than sham-operated control in hamster cheek pouch. Topical tanshinone increased normalized arteriolar diameter from 1.0 to 1.47±0.08 in the cremaster muscle of control mice and to 1.12±0.13 in cremasters of eNOS-knockout mice. In ECV 304 cells transfected with eNOS-green fluorescent protein, tanshinone increased eNOS protein expression 1.35±0.05 and 1.85±0.07 -fold above control after 5 min and 1 hr application, respectively. Tanshinone also increased eNOS phosphorylation 1.19±0.07 and 1.72±0.20 -fold relative to control after 5 min and 1 hr application. Our data provide a basis to understand the action of a Chinese herb used in alternative medicine. We conclude that eNOS stimulation is one mechanism by which tanshinone induces vasodilatation and reduces blood pressure.
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