Effect Of Tetrandrine On Arterial Baroreflex Function In Sinoaortic Denervated Rats

Objective:Hypertension, with complicated mechanism, correlates with the damage of a series of organs, such as brain, heart, kidneys and so on. It has been widely reported that blood pressure variability (BPV) is increased and arterial baroreceptor reflex (ABR) defect exists in hypertensive human and animals. Furthermore, it was shown that BPV was positively related to the severity of organ damage in hypertensive patients and in SHR. Removal of the carotid sinus and aortic arch baroreceptor (SAD) results in the inability to buffer moment-to-moment changes in pressure bringing about arterial pressure lability. Lability is the most consistent feature after sinoaortic denervation and has been shown to exist in all species in which SAD has been studied. Despite the marked variability of arterial pressure,24-h mean pressure level is unchanged or only slightly increased in SAD animals. It was demonstrated that the increased BPV without the elevation of 24-h BP level after SAD induced organ damage. Heart rate variability (HRV), which helps understanding the mechanism of ABR and BPV, could reflex the function of autonomic nerve. In this research, we give Tetrandrine (Tet), an active component of traditional Chinese drug, which could decrease blood pressure (BP), to SAD rats to see the effect on BPV, baroreflex sensitivity (BRS) and HRV.Method:Male Sprague-Dawley(SD) rats from 230—250g. All the rats bringing into statistics were operated as SAD models. Three Tet dosage groups compared with two groups (10 rats respectively) using nifedipine and saline respectively were designed. With a computerized analysis system of BP, We studied the effects of Tet on BPV, ABR and HRV in SAD rats in conscious unrestrained state. Hemodynamic indexes were recorded. SBP, DBP and HP (refer to the time interval between two successive occurrences of SBP) are the average values of these parameters obtained beat by beat during the test period. BPV and HRV were defined as the standard deviation of the SBP, DBP and HP and were calculated from each beat during the test periods for each animal. BRS were measured by a bolus injection of AngⅡ, which was used to induce an elevation of BP. The dose of AngⅡ was adjusted to raise SBP between 20 and 40 mmHg. There is a delay between the elevation in BP (stimulus) and the prolongation of HP (response) for the arterial baroreflex. So, HP was plotted against SBP with five shifts for linear regression analysis. The slope of HP/SBP is expressed as BRS (msec/mmHg). Data are expressed as the mean±SD. Comparison between pre-and post-drug were made by paired t-test, whereas comparisons between two groups were made by group t test. The test of BRS was made by linear regression.Results:1. Tet could decrease BP in SAD rats in conscious unrestrained state without significant change in heart period. However, heart rate (HR) increased significantly in Nif group.2. Tet reduces BPV significantly in SAD rats, and the effect could last for 14h at least. Tet in 15mg/kg reduced the BPV with a background of insignificant antihypertensive effect in SBP. There's no significant change of BPV in 0-2h after Nif infusion, while a significantly high BPV level could be seen in 3-14h.3. Tet could intensify the ABR activity, but the post-drug ABR changes could not reflex the way the BPV change. In 60mg/kg group, ABR was still in a more sensitive state after 14 hours. Nif (5mg/kg) could weaken the ABR function.4. No regular significant effect had been seen on HRV after drug infusion.Conclusion:1. Tet injected could reduce BPV in SAD rats in conscious unrestrained state, and the effect last for 14h at least. Tet in 15mg/kg reduced the BPV with a background of insignificant antihypertensive effect in SBP. Nif decrease BP, but increase HR significantly. 2. Tet could intensify the ABR activity. In 60mg/kg group, BRS was still in a more sensitive state after 14 hours. Nif (5mg/kg) could reduce BRS. 3. Tet could decrease the BP of SAD rats in conscious unrestrained state. Slight changes had been seen in HR. 4. Tet and Nif had no significant effect on HRV in SAD rats.