A novel animal model for motion sickness and its first application in rodents.

The present work was designed to establish a novel animal model for motion sickness (MS) in rodents and to evaluate the effects of a combination of scopolamine and modafinil on MS with this novel method. It was found that the rats and mice presented several symptoms induced by rotation such as, piloerection, tremble, urinal and fecal incontinence. As the rats and mice are lack of emesis response to rotation, we used a score based on abovementioned symptoms as an index for the severity of MS in rodents. MS index was determined in 260 mice with this novel method. It was found that the distribution of MS index was normal (W=0.99; P=0.23. P>0.05 considered values' normal distribution). The effects of scopolamine on MS were studied in mice and rats. It was found that scopolamine significantly decreased MS index at the dose of 0.3 mg/kg in mice and 1.0 mg/kg in rats. Finally, the effects of a combination of scopolamine and modafinil were observed with this novel method in rats. It was found that the efficacy of the combination (5.0+5.0 mg/kg) was greater than the single drugs (10 mg/kg). Even the smallest dose of the combination (0.5+0.5 mg/kg) had a similar effect to large dose of scopolamine or modafinile when they were used alone. In conclusion, this animal model is suitable for MS study in rats and mice and the combination of scopolamine and modafinil might be a new method to treat or prevent MS.

Contribution of blood pressure variability to the effect of nitrendipine on end-organ damage in spontaneously hypertensive rats.

OBJECTIVE: It has been proposed that blood pressure variability (BPV) is positively related to end-organ damage (EOD) in hypertension. The present work was designed to observe the effects of long-term treatment with nitrendipine and hydralazine on BPV and EOD in spontaneously hypertensive rats (SHR), to examine the hypothesis that lowering BPV with an antihypertensive drug is an important factor in organ protection. DESIGN AND METHODS: Drugs were mixed in rat chow. After 4 months of drug administration, blood pressure was recorded continuously in conscious freely moving rats for 24 h. The heart, kidneys, and brain were then isolated and examined. RESULTS: It was found that nitrendipine significantly decreased blood pressure and BPV, and significantly decreased EOD score in SHR. Hydralazine decreased blood pressure, but did not lower BPV. No effect on EOD was found in hydralazine-treated rats. In control rats (n = 38), EOD score was weakly related to systolic blood pressure (r = 0.331, P < 0.05) and closely related to long-term systolic BPV (r = 0.551, P < 0.01). In nitrendipine-treated rats, EOD score was closely related to long-term systolic BPV (r = 0.602, P < 0.01), but not to BP level (r = 0.174, P > 0.05). CONCLUSION: BPV plays an important role in the organ-protecting effects of nitrendipine.

The survival time post-cecal ligation and puncture in sinoaortic denervated rats.

Arterial baroreflex (ABR) function is an important determinant factor in prognosis of many cardiovascular diseases. The present work was designed to study the relationship between ABR function and the survival time of septic shock in a cecal ligation and puncture (CLP) rat model. The dysfunction of ABR was introduced by sinoaortic denervation (SAD). It was found that the survival time after CLP was significantly reduced in SAD rats compared with sham-operated rats (12.7 +/- 2.92 hours versus 15.0 +/- 4.01 hours; P < 0.05). Furthermore, significant differences were also seen when the results were expressed by Kaplan-Meier survival curves. Compared with the baseline values, both noradrenaline and adrenaline significantly increased in both SAD and Sham groups after CLP, but we found the baseline of noradrenaline was significantly elevated in SAD rats. In addition, the TNF-alpha, noradrenaline, and adrenaline levels of the SAD group were significantly higher than those of the Sham group at 5 hours post-CLP. In conclusion, the present work demonstrates that ABR function was related to the survival time in CLP-induced lethal shock model. The loss of inhibition in the sympathetic activity and in the release of some inflammatory cytokines during CLP-induced septic shock related to baroreflex and/or chemoreflex dysfunction may be the mechanisms involved in the poorer prognosis in septic shock.

Synergism of hydrochlorothiazide and nitrendipine on reduction of blood pressure and blood pressure variability in spontaneously hypertensive rats.

AIM: To investigate the possible synergism of hydrochlorothiazide and nitrendipine on reducing both blood pressure (BP) and blood pressure variability (BPV) in spontaneously hypertensive rats (SHR). METHODS: Seventy animals were randomly divided into seven groups. The doses were 5 and 10 mg/kg for nitrendipine, 10 and 20 mg/kg for hydrochlorothiazide and 10 + 5, 20 + 10 mg/kg, respectively, for the combination of these two drugs and 0.8% carboxymethylcellulose as control. The drugs were given via a catheter of gastric fistula. BP was then continuously recorded for 5 h from 1 h before drug administration to the end of 4th hour after drug administration, in conscious and freely moving rats. RESULTS: The effects on both BP and BPV reduction of the combination of hydrochlorothiazide and nitrendipine were greater than the single drug in SHR. The two drugs possessed an obvious synergism on both systolic blood pressure (q = 1.79 with small dose and q = 1.23 with large dose) and systolic blood pressure variability reduction (q = 1.79 with small dose and q = 1.39 with large dose) in SHR. CONCLUSION: The present work clearly demonstrated that there was a synergistic effect between hydrochlorothiazide and nitrendipine in lowering and stabilizing BP in SHR.

Apoptosis is involved in the cardiac damage induced by sinoaortic denervation in rats.

1. The arterial baroreflex plays an important role in the maintenance of the stability of blood pressure. Sinoaortic denervation (SAD) produces severe organ damage in rats. The present study was designed to investigate whether apoptosis, which is a ubiquitous physiological mode of cell death distinct from cell mortality induced by injury and necrosis, is involved in SAD-induced cardiac damage. 2. Male Sprague-Dawley rats (10 weeks old) were used. Rats underwent SAD (n = 9) or sham operation (n = 10). Sixteen weeks after operation, the heart tissues were taken for investigations including electron microscopy, immunohistochemistry, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) and reverse transcription-polymerase chain reaction (RT-PCR). 3. Cardiac hypertrophy and fibrosis was found in SAD rats. The number apoptotic cardiomyocytes was increased in SAD rats compared with sham-operated rats. 4. The expression of Bcl-2mRNA and protein (an inhibitory factor of apoptosis) in cardiomyocytes was decreased in SAD rats. In contrast, the expression of Bax, Fas and Fas ligand mRNA and proteins (promoters of apoptosis) in cardiomyocytes was significantly increased in SAD rats. 5. In conclusion, the present study reveals a high level of apoptosis in cardiomyocytes in SAD rats. It is proposed that apoptosis is involved in SAD-induced cardiac damage.

Ketanserin stabilizes blood pressure in conscious spontaneously hypertensive rats.

1. It has been demonstrated that blood pressure variability (BPV) is increased in hypertension and related to organ damage. It will be important to lower BPV in the treatment of hypertension. The present study was designed to investigate the effect of ketanserin, a 5-HT2A receptor antagonist with a weak alpha1-adrenoceptor blocking effect, on BPV in conscious spontaneously hypertensive rats (SHR). 2. It was found that ketanserin decreased blood pressure (BP) and BPV in SHR when administered intravenously (3 mg/kg, i.v.). Ketanserin decreased BPV, but not the BP level, when administered intracerebroventricularly (50 microg/rat, i.c.v.). 3. Prazosin, an alpha1-adrenoceptor antagonist, lowered BP but did not affect BPV when given either i.v. (0.5 mg/kg) or i.c.v. (30 microg/rat). Ritanserin (0.625 mg/kg, i.v.; 40 microg/rat, i.c.v.), a 5-HT2A receptor antagonist, decreased BPV only when administered i.c.v. and did not modify the BP level. 4. Ketanserin enhanced arterial baroreflex function in SHR when given either i.v. or i.c.v. 5. The stabilizing effect of ketanserin on BP was persistent when administered intragastrically. This administration route is similar to oral administration clinically. 6. It is concluded that ketanserin is an antihypertensive agent with an effect of reducing BPV. This effect is mainly mediated by central 5-HT2A receptors and is probably attributable to the restoration of arterial baroreflex function.