Ginkgo biloba extract attenuates the development of hypertension in deoxycorticosterone acetate-salt hypertensive rats.
1. We examined the effects of Ginkgo biloba extract (GBE) on the development of hypertension, platelet activation and renal dysfunction in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Both DOCA-salt hypertensive rats and normotensive rats were fed a 2% GBE diet for 20 days. Blood pressure (BP) was measured by two methods, namely by the tail-cuff and telemetry methods. 2. Development of hypertension was attenuated in rats fed a 2% GBE diet. In addition, an increase in heart weight, an indicator of sustained high BP, was inhibited significantly by feeding of the GBE diet. 3. Decreases in 5-hydroxytryptamine content in platelets, a marker of platelet activation in vivo associated with hypertension, were also prevented by feeding of the GBE diet. Ginkgo biloba extract itself did not inhibit ADP- and collagen-induced platelet aggregation examined in vitro. Feeding of the GBE diet tended to inhibit increases in plasma urea nitrogen due to hypertension. 4. The telemetry study demonstrated that BP and heart rate (HR) showed a clear circadian rhythm and the antihypertensive effect of GBE was prominent in the daytime, a resting period for rats. This anti-hypertensive effect of GBE was not detected in normotensive rats. In contrast, the inhibitory effect of GBE on HR was independent of time and was observed in both normotensive and hypertensive rats. 5. These results indicate that GBE has an anti-hypertensive and bradycardiac action, which are time dependent and independent, respectively. Thus, it appears that the chronopharmacological action of GBE may be ascribed not to pharmacokinetic factors, but rather to a circadian susceptibility rhythm to GBE in DOCA-salt hypertensive rats.
Umegaki
K
K
Division of Applied Food Research, The National Institute of Health and Nutrition, Tokyo, Japan. umegaki@nih.go.jp
Shinozuka
K
K
Watarai
K
K
Takenaka
H
H
Yoshimura
M
M
Daohua
P
P
Esashi
T
T
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001795:Blood Pressure Determination / Q000379:methods; D001806:Blood Urea Nitrogen; D002940:Circadian Rhythm; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020441:Ginkgo biloba / Q000737:chemistry*; D006321:Heart / Q000187:drug effects / Q000254:growth & development; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects / Q000254:growth & development; D008297:Male; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood; D012965:Sodium Chloride / Q000494:pharmacology*; D013599:Systole; D013686:Telemetry
D010936:Plant Extracts; D012701:Serotonin; D003900:Desoxycorticosterone; D012965:Sodium Chloride