| Hypertension is one of the most popular cardiovascular diseases. Medication is a therapy of non-physiologic regulation on blood pressure, and usually produces many side effects. Our previous studies showed a chip system can successfully control blood pressure in normal rabbits, rats and spontaneously hypertensive rats (SHR). In the present study, in order to investigate the anti-hypertensive effects of the chip system in secondary hypertension, we tested the depressor effects of the chip system in anaesthetic two-kidney, one-clip (2K1C) renovascular hypertensive rats and compared with sham-operated rats. The effects of the chip system on the mean arterial pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), the plasma norepinephrine concentration and plasma renin concentration, the baroreflex Sensitivity (BRS) and cardiac contractile state were determined in these rats. The rats were randomly subjected to two-kidney, one-clip (2K1C) to induce renovascular hypertension or sham operation.Each rat was anesthetized with intraperitoneal injection of urethane (1.2 g/kg). The left aortic depressor nerve (ADN) was isolated and identified. A pair of thin silver electrodes was hooked around the nerve preparing for the electrical stimulations. The chip system receives the information of arterial pressure from transducer in the right femoral artery. The waves of arterial pressure are sampled, operated and processed in the chip system. Then, electrical signals with different frequencies are produced by the chip system to stimulate the left ADN. The plasma norepinephrine concentration and plasma renin concentration were measured by enzyme-linked immunosorbent assay (ELISA). To determine the left ventricle (LV) pressures, the transducer was sent into LV. The left ventricle end-diastolic pressure (LVEDP), left ventricle developing pressure (LVDP) and maximal rise rate of the left ventricle pressure (LVdP/dtmax) were determined to provide a functional index of cardiac contractile state. The baroreceptor reflex was induced by repeated bolus intravenous injections of graded doses of phenylephrine. The BRS was evaluated in each rat by regression line for the relationship between the changes in HR and the changes in MAP for each data point obtained with graded injection of phenylephrine. The slope of the line expressing the relationship (beats·min-1·mmHg-1) was used as an index of the BRS. The primary findings were as following:1. The MAP was much higher in 2K1C rats than in sham-operated rats (138.2±2.5 vs. 97.2±4.3 mmHg, P<0.05). Stimulation of the ADN with the chip system normalized the MAP in 2K1C rats(138.2±2.5 mmHg vs. 98.6±7.8 mmHg, P<0.05). The chip system regulation caused a greater fall in MAP (-47.1±2.4 mmHg vs. -6.9±4.0 mmHg, P<0.05), but a smaller fall in HR (-28.8±12.7 bpm vs. -51.2±9.4 bpm, P<0.05) in 2K1C rats than in sham-operated rats.2. The baseline RSNA was much higher in 2K1C rats than in sham-operated rats (75.4±4.7% vs. 46.7±4.3%, P<0.05). Stimulation with the chip system decreased the RSNA in both 2K1C rats and sham-operated rats. There was no significant difference in the percent change of the RSNA caused by the stimulation between 2K1C rats and sham-operated rats (-38.1±2.7% vs. -36.9±3.2 %, P>0.05).3. The plasma norepinephrine concentration was much higher in 2K1C rats than in sham-operated rats (1827.3±45.9pg/ml vs. 760.7±28.6pg/ml, P<0.05 ). The chip system regulation normalized the plasma norepinephrine concentration in 2K1C rats (1827.3±45.9 pg/ml vs. 922.3±124.5 pg/ml, P<0.05).4. The BRS was much lower in 2K1C rats than in sham-operated rats (-1.53±0.24beats·min-1·mmHg-1 vs.-3.15±0.54 beats·min-1·mmHg-1, P<0.05). Stimulation of the ADN with the chip system significantly increased the BRS in 2K1C rats, but not in sham-operated rats. However, the BRS was still much lower in 2K1C rats than in sham-operated rats during the stimulation of the chip system (-1.94±0.30 beats·min-1·mmHg-1 vs. -3.47±0.49 beats·min-1·mmHg-1, P<0.05).5. There was no significant change in plasma renin concentration in 2K1C rats during the stimulation of the chip system (4.03±0.6ng/ml vs. 4.88±0.8 ng/ml, P>0.05).6. The LVDP and LVdP/dtmax were significantly higher in 2K1C rats than in sham-operated rats (LVDP: 172.7±9.8 mmHg vs. 131.5±9.9 mmHg, P<0.05, LVdP/dtmax: 5314.4±318.9 mmHg/sec vs. 3979.1±219.6 mm Hg/sec, P<0.05). Stimulation with the chip system normalized the LVDP (121.1±7.9 mmHg) and LVdP/dtmax (4023.1±212.8 mmHg/sec) in 2K1C rats. The stimulation did not cause any significant effect on LVEDP in either 2K1C or sham-operated rats.The present study showed that the closed-loop chip system achieved a good anti-hypertensive effect in the acute experiment of 2K1C rats. The chip system caused a greater fall in MAP, but a smaller fall in HR in 2K1C rats than in sham-operated rats, suggesting that the depressor effect induced by the chip system was less dependent on its bradycardia effect in 2K1C rats than in sham-operated rats. The stimulation with the chip system decreased the enhanced sympathetic outflow in 2K1C rats. The plasma norepinephrine concentration was much higher in 2K1C rats than in sham-operated rats, the chip system regulation normalized the plasma norepinephrine concentration in 2K1C rats; The BRS was improved during the chip resetting in 2K1C rats, which might be explained that the chip system strengthened the baroreflex by establishing a closed-loop control system and there was no significant difference in the BRS before and after the chip resetting, which indicated the activation of baroreflex didn't affect the baroreflex function in 2K1C rats in the acute experiment. There was no significant change in plasma renin concentration in 2K1C rats during the stimulation of the chip system. The stimulation of ADN with the chip system normalized the LVDP and LVdP/dt in 2K1C rats, indicating that the stimulation with the chip system decreased the cardiac contractility. During the stimulation, the LVDP, LVEDP and LVdP/dt in either 2K1C rats or sham-operated rats were in normal range, suggesting that the application of the chip system did not cause obvious hemodynamic abnormalities.In conclusion, the chip system could effectively control blood pressure in2K1C rats in the acute experiment. It improves the baroreflex sensitivity,normalizes the enhanced sympathetic activity and the plasmanorepinephrine concentration as well as the cardiac contractile state in2K1C rats. |
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