Effects Of Ginkgolide B On Carotid Sinus Baroreflex And Baroreceptor Activity In Anesthetized Male Rats

Ginkgo biloba extract (GBE) is a natural compound derived from the Ginkgo biloba and mainly composed of 6% terpene lactones and 24% flavonol glycosides. Ginkgolide B is a major active component of terpene lactones. Numerous studies have showed ginkgolide B, a potent antagonist of platelet-activating factor, exhibits a wide range of biological effects. Ginkgolide B has been used for cardiovascular and cerebrovascular disease by improving blood flow, reducing ischemia-reperfusion injury or inhibiting platelets. Ginkgolide B produces vasorelaxation, but the mechanism of ginkgolide B on vascular smooth muscles function is still essentially unknown. Some other experiments have already demonstrated that ginkgolide B decreases L-type calcium current (ICa,L) in a concentration-dependent manner and partially inhibits calcium overload during ischemia. Ginkgolide B may shorten the action potential duration in a concentration-dependent manner which mainly due to the increase of the delayed rectifier potassium current (Ik) in single ventricular myocytes by using patch-clamp techniques. It is well known that baroreflex is a major way to modulate blood pressure. The effects of ginkgolide B on carotid sinus baroreceptor activity and baroreflex have not been reported yet; the goals of the present research were to observe these effects of ginkgolide B.1 Effects of ginkgolide B on carotid sinus baroreflex in anesthetized male ratsObjective: To study the effects of ginkgolide B on carotid sinus baroreflex (CSB).Methods: The functional curve of carotid sinus baroreflex was measured by recording the changes of arterial pressure in 30 anesthetized male rats with isolated perfusing carotid sinus.Results: (1) ginkgolide B (0.1, 1, 10μmol/L) inhibited CSB, which shifted the functional curve of the baroreflex to the right and upward, with a marked decrease in peak slope (PS) and reflex decrease (RD) in blood pressure in a concentration-dependent manner. PS decreased from 0.46±0.01 to 0.37±0.01, 0.32±0.01, 0.23±0.01 respectively. RD decreased from (46.50±1.38) mmHg to (40.00±0.89), (34.83±1.94), (28.33±1.50) mmHg; threshold pressure (TP) increased from (65.46±1.76) mmHg to (71.66±0.84), (75.18±1.56), (84.56±1.76) mmHg; equilibrium pressure (EP) increased from (93.94±0.82) mmHg to (96.28±1.10), (98.29±0.90), (100.64±1.01) mmHg; saturation pressure (SP) increased from (186.33±2.73) mmHg to (192.00±2.37), (195.83±2.04), (205.17±2.14) mmHg respectively. (2) Pretreatment with Bay K8644 (500 nmol/L), an agonist of L-type calcium channel, completely eliminated the effects of ginkgolide B (1μmol/L) on the CSB. (3) Pretreatment with tetraethylammonium (TEA, 1 mmol/L), an inhibitor of potassium current, completely abolished the above effects of ginkgolide B (1μmol/L) on CSB.Conclusion: Ginkgolide B inhibits the CSB in anesthetized male rats, which is mediated by decreased calcium influx and increased potassium efflux in baroreceptor nerve ending.2 Effects of ginkgolide B on carotid sinus baroreceptor activity in anesthetized male ratsObjective: To study the effects of ginkgolide B on carotid baroreceptor activity (CBA).Methods: The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in 30 anesthetized male rats with perfused isolated carotid sinus.Results: (1) ginkgolide B (0.1, 1, 10μmol/L) inhibits CBA, which shifted FCCB to the right and downward. There was a marked decrease in peak slope (PS) and peak integral value (PIV) of carotid sinus nerve charge in a concentration-dependent manner. PS decreased from (3.08±0.11) %mmHg-1 to (2.52±0.06), (2.22±0.05), (2.00±0.07) %mmHg-1, respectively. PIV decreased from (331.17±3.76) % to (273.67±4.03), (243.67±3.72), (213.67±5.16) %, respectively; threshold pressure (TP) increased from (44.16±1.50) mmHg to (51.81±1.28), (58.67±3.02), (63.42±1.44) mmHg; saturation pressure (SP) increased from (161.33±2.07) mmHg to (172.33±1.03), (181.33±2.16), (188.17±1.17) mmHg. (2) Pretreatment with Bay K8644 (500 nmol/L), an agonist of L-type calcium channel, completely eliminated the effects of ginkgolide B (1μmol/L) on CBA. (3) Pretreatment with tetraethylammonium (TEA, 1 mmol/L), an inhibitor of potassium current, completely abolished the above effects of ginkgolide B (1μmol/L) on CBA.Conclusion: Ginkgolide B inhibits CBA in anesthetized male rats, which is mediated by decreased calcium influx and increased potassium efflux in baroreceptor nerve ending.