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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.

Aim: The present work was designed to investigate the effects of nine commonly used antihypertensive drugs on blood pressure (BP) and blood pressure variability (BPV) in conscious sinoaortic-denervated (SAD) rats., Methods: Seventy-two SAD rats were randomly divided into nine groups. They were respectively given nifedipine 3 mg/kg, nitrendipine 5 mg/kg, amlodipine 1 mg/kg, clonidine 10 mug/kg, prazosin 0.5 mg/kg, atenolol 20 mg/kg, telmisartan 20 mg/kg, hydrochlorothiazide 40 mg/kg or captopril 50 mg/kg. The drugs were given via a catheter previously implanted into the stomach. BP was recorded for 5 h from 1 h before drug administration to 4 h after drug administration in conscious, freely moving rats., Results: It was found that all these nine drugs significantly decreased BP in SAD rats. Six of these drugs (nifedipine, nitrendipine, amlodipine, clonidine, prazosin and atenolol) significantly decreased BPV in SAD rats, but the remaining three drugs did not. Clonidine and atenolol increased the heart period and the others did not. No drugs affected the heart period variability., Conclusion: Among nine antihypertensive drugs from different classes, calcium antagonists and sympathetic inhibitors decreased BPV in SAD rats.

1. One unusual and interesting feature of spontaneously hypertensive rats (SHR) is their salt preference. This behaviour is known to be independent of blood pressure. 2. Arterial baroreflex (ABR) function is impaired in SHR. Therefore, the present study was designed to explore the relationship between ABR function and salt preference in rats. 3. Twenty-seven SHR, aged 11 months, were used. Blood pressure and baroreflex sensitivity (BRS) were determined in conscious, freely moving SHR after the measurement of salt preference. It was found that BRS did not relate to the salt preference in these rats. 4. Another group of normotensive Sprague-Dawley rats, aged 10 weeks, underwent either sinoaortic denervation (SAD) or sham operation. Salt preference was determined before and 4 weeks after SAD. Sinoaortic denervation did not alter salt preference in normotensive rats. 5. It is concluded that ABR function does not influence the salt preference in rats.

1. The present work was designed to observe the early structural changes in the aortic wall in Sprague-Dawley rats 1, 2 and 4 weeks after sinoaortic denervation (SAD). 2. Rats were examined 1, 2 and 4 weeks after SAD. Blood pressure (BP) was recorded in the conscious state. The thoracic aortas were taken for investigations, including: light microscopy, electron microscopy, immunohistochemistry and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL). 3. Blood pressure variability (BPV) was significantly increased in the SAD groups 1, 2 and 4 after the operation when compared with the sham-operated ones. 4. Two weeks after SAD the percentage proportion of smooth muscle cell density (SMC%) was obviously increased. 5. Four weeks after SAD: the SMC%, percentage proportion of collagen density (CD%) and aortic wall thickness (WT) were obviously increased with vascular smooth muscle cells blebbing concomitantly. Endothelial cells showed degenerative changes and swelling with blebbing of the cell membrane and increased condensation of peripheral nuclear chromatin and cytoplasmic vacuolization. It was also found that the number of apoptotic endothelial cells was increased and expression of eNOS was reduced. 6. This is the first study that shows the time-course of aortic wall and endothelial cell changes induced by SAD. Increased BPV might be the priming factor in the development of organ damage induced by SAD.

Aim: To test the synergistic effects of atenolol and amlodipine on lowering blood pressure (BP) and reducing blood pressure variability (BPV) in 2-kidney, one-clip (2K1C) renovascular hypertensive rats., Methods: Forty-eight 2K1C renovascular hypertensive rats were randomly divided into 6 groups. They were respectively given 0.8% carboxymethylcellulose sodium (control), atenolol (10.0 mg/kg), amlodipine (1.0 mg/kg), and combined atenolol and amlodipine (low dose: 5.0+0.5 mg/kg; intermediate dose: 10.0+1.0 mg/kg; high dose: 20.0+2.0 mg/kg). The drugs were given via a catheter in a gastric fistula. BP was recorded for 25 h from 1 h before drug administration to 24 h after administration., Results: Compared with BP before medication, all 3 doses of combined atenolol and amlodipine significantly decreased the BP at 24 h after administration, except for the low dose on diastolic BP. Compared with the control group, all 3 doses of combined atenolol and amlodipine significantly reduced the average BP levels for the 24 h period after administration; furthermore, the high and intermediate doses also significantly decreased the BPV levels for the same period. The q values calculated by probability sum analysis for systolic and diastolic BP for the 24 h period after administration were 2.29 and 1.45, respectively, and for systolic and diastolic BPV for the same period they were 1.41 and 1.60, respectively., Conclusion: There is significant synergism between atenolol and amlodipine in lowering and stabilizing BP in 2K1C renovascular hypertensive rats.

Aim: To investigate the blood pressure (BP), baroreflex sensitivity (BRS), and organ damage in hybrids of spontaneously hypertensive rats and Sprague-Dawley rats., Methods: Spontaneously hypertensive rats and Sprague-Dawley rats were crossbred, and the F1 hybrids were inbred randomly to produce an F2 generation. At the age of 52 weeks, the F1 and F2 hybrids were tested to determine BP and BRS in a conscious state. Histopathological examinations were carried out after BP recording and BRS studies., Results: BP and BRS were not different in F1 and F2 hybrids. BRS was inversely related to systolic BP (SBP) in male, female, or whole populations of hybrids. Quantitatively, BRS values were one-third determined by SBP level (the determinant coefficient was 0.326). The indexes for left ventricular hypertrophy, aortic hypertrophy, and renal damage were all positively related to BP, and negatively related to BRS. In multiple-regression analysis, left ventricular and aortic hypertrophy and glomerulosclerosis score were all most significantly associated with lower BRS and higher systolic BP. The contribution of BRS to left ventricular and aortic hypertrophy and glomerulosclerosis was greater than that of SBP., Conclusion: The present work with hybrid rats demonstrated quantitatively that the BRS value was one-third determined by SBP level. Both BP level and BRS value contributed greatly to the hypertensive organ damage. However, the contribution of BRS to the hypertensive organ damage was greater than that of BP level in these rats.

Aim: To demonstrate and compare hemodynamic phenotypes of blood pressure (BP), blood pressure variability (BPV) and baroreflex sensitivity (BRS) in genetic hypertensive rats., Methods: BP was recorded continuously in conscious, freely moving rats using a computerized technique. BPV was expressed as the standard deviation of beat-to-beat BP values during a 1-h period. BRS was determined by measuring the heart period prolongation in response to the elevation in BP produced by an intravenous injection of phenylephrine., Results: Body weight and heart period were not different between spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHR-SP) at the age of 15 weeks. The BP level was markedly higher in SHR-SP than SHR, whereas there were no significant differences in BPV and BRS. Quantitatively, systolic, diastolic and mean BP were significantly elevated by 36.9%, 42.9% and 39.5%, respectively, in SHR-SP compared with SHR (P < 0.01). However, their variabilities were elevated only by 14.0%, 0.4% and 10.1%, respectively, without statistical significance (P > 0.05)., Conclusion: BPV and BRS were not changed in parallel with the BP alterations in SHR and SHR-SP.

1. The present study was designed to investigate the haemodynamic features and morphological changes in experimentally hypertensive rat models. 2. Sprague-Dawley rats were used to prepare the experimentally hypertensive models, including two-kidney, one-clip renovascular hypertensive (2K1C) rats, deoxycorticosterone acetate salt hypertensive (DOCA) rats and N(G)-nitro-l-arginine methyl ester-induced hypertensive (l-NAME) rats. Six weeks after the induction of hypertension, 24 h blood pressure was recorded and blood pressure variability (BPV) expressed by 24 h (or 12 h in the daytime and night-time study) standard deviation of the variables was calculated. Then, cardiac baroreflex sensitivity (BRS) was determined and four endogenous factors (tumour necrosis factor-alpha, interleukin-1beta, angiotensin II and endothelin-1) were measured. Finally, morphological changes were examined. 3. It was found that an increase in BPV and a decrease in BRS were accompanied by an elevation of blood pressure in all three hypertensive models. The DOCA rats had the highest BPV, whereas the l-NAME rats had the lowest BRS. 4. Morphological changes were similar in DOCA and l-NAME rats and the cardiac changes were relatively slight in 2K1C rats. Tumour necrosis factor-alpha was increased in all the three models, especially in DOCA rats. Endothelin-1 was higher in DOCA rats and angiotensin II was increased in 2K1C rats and decreased in DOCA rats. 5. In conclusion, increased BPV and decreased BRS accompanied the elevation of blood pressure in all three hypertensive models. The DOCA rats had the highest BPV and the l-NAME rats had the lowest BRS. Obvious organ damage was seen in all three hypertensive models 6 weeks after the induction of hypertension.

Aim: To examine the effects of urotensin II, a recently discovered endogenous peptide, on coronary flow (CF), cardiac function, and endothelial nitric oxide synthase (eNOS) expression in isolated rat hearts., Methods: Heart was isolated and perfused retrogradely via the aorta in Langendorff mode. Rat urotensin II was administered in the perfusion solution. The eNOS content in myocardium was determined by Western blot., Results: Rat urotensin II had no effect on the heart rate, left ventricular systolic pressure, left ventricular end-diastolic pressure, or +/-dp/dt(max). While rat urotensin II dose-dependently increased CF. CF was increased by 11.43 %, 6.67 %, 6.62 %, 6.56 %, 6.36 %, and 5.86 % respectively in a time-dependent manner at 5, 10, 15, 20, 25, and 30 min after injection of rat urotensin II 6.66 x 10(-2) microg. The maximal effect on CF was found at 5 min following urotensin II administration. N(G)-nitro-L-arginine methyl ester (L-NAME) did not prevent the increased CF in response to urotensin II. Rat urotensin II dose-dependently increased the cardiac eNOS protein expression and this effect was not inhibited by L-NAME., Conclusion: Rat urotensin II did not alter cardiac function but increased CF and the amount of myocardial eNOS protein in the isolated rat heart. The increased CF was independent of the involvement of eNOS.

It is known that the caudal ventrolateral medulla (CVLM) plays an important role in controlling blood pressure and mediating the cardiovascular effects of centrally acting antihypertensive drugs such as clonidine. Recently, the effect of clonidine was believed to be related to the functional states of N-methyl-D-aspartate (NMDA) receptors. The present work was designed to observe the interactions between clonidine and NMDA receptor in the CVLM. Unilaterally injected clonidine (6 nmol) into the CVLM not only produced a pressor action, but also effectively (P<0.01, n=8) antagonized the decreases in both mean arterial pressure (MAP) (-22.3+/-5.0 to -7.9+/-2.3 mmHg) and heart rate (HR) (-31.9+/-5.9 to -10.3+/-2.7 beats/min) evoked by L-glutamate in the CVLM. Unilaterally injected NMDA receptor antagonist MK801 (200 pmol) into the CVLM significantly increased MAP by 26.5+/-3.7 mmHg and HR by 37.1+/-7.6 beats/min, and completely (P<0.01, n=10) abolished the pressor effect (16.1+/-6.6 to 1.5+/-2.8 mmHg) of clonidine in the CVLM. In conclusion, these findings show that NMDA receptors within the CVLM contribute to clonidine-induced action, and suggest that the CVLM plays an important role in the interaction between clonidine and NMDA receptors.

1. Biventricular hypertrophy has been described in a high blood pressure variability (BPV) model of sinoaortic-denervated (SAD) rats without systemic hypertension. To explore the possible involvement of the lung in SAD-induced right ventricular hypertrophy (RVH), we examined lung morphology, in addition to systemic haemodynamics and ventricle morphology, in Wistar-Kyoto rats 32 weeks after SAD. 2. In Wistar-Kyoto rats 32 weeks after SAD, there existed a substantial elevation in BPV, with no change in the average level of arterial pressure. Biventricular hypertrophy following SAD was characterized by a greater hypertrophy in right than left ventricles; both absolute and normalized right ventricular weights were significantly increased by 22 and 27%, respectively, and only normalized left ventricular weight was significantly increased by 12%. No infarcts were found in any ventricles examined. 3. In the lung, the most prominent change following SAD was pulmonary vasculopathy, including wall thickening, perivascular fibrosis and cell infiltration. In pulmonary arteries with an internal diameter of 70-130 microm, the external diameter, wall thickness and wall thickness to internal diameter ratio were increased in SAD compared with control rats. 4. There was no correlation between right and left ventricular weights. In contrast with BPV-correlated left ventricular weight, right ventricular weight was correlated with the wall thickness of the pulmonary artery, but not with BPV. 5. These findings suggest that greater RVH following SAD is associated with pulmonary vasculopathy, but is not secondary to the left ventricular problems or high BPV.

Aim: The present study was designed to test a hypothesis that nonfatal ventricular arrhythmia such as ventricular premature beats (VPB) is a contributing factor in the elevation of blood pressure variability (BPV)., Methods: Blood pressure (BP) and electrocardiogram were continuously recorded. The relation between VPB and BPV was observed under conscious state in chronic myocardial infarction (MI) rats one month after ligation of the left coronary artery, and further verified under anesthetized state in rat model of ventricular arrhythmia produced by acute intravenous infusion of aconitine., Results: MI rats exhibited a big difference in the count and pattern of VPB, and were divided into no VPB, occasional VPB, and frequent VPB groups. Among the three groups, there were no differences in BP, heart period (HP), and MI size. However, BPV was markedly higher in frequent not occasional VPB rats, and HP variability (HPV) was larger in both frequent and occasional VPB rats, when compared with no VPB rats. In the whole population of MI rats, BPV was positively correlated with VPB and HPV, not with BP, HP and MI size. Infusion of aconitine had no effect on BP, HP, BPV, and HPV during the period without VPB. Frequent VPB after several minutes of aconitine infusion induced significant increase in BPV and HPV with no change in BP and HP. BPV was also positively correlated with VPB and HPV, not with BP and HP. Hemodynamics in aconitine-evoked ventricular tachycardia was characterized as lower BP, higher BPV, and higher HPV., Conclusion: High BPV can be caused by frequent not occasional VPB in rats.

Aim: Computerized analysis of blood pressure in conscious freely moving rats is a sound technique for physiological and pharmacological studies. The present work, based on this technique, was designed to introduce two useful methods for the evaluation of antihypertensive drugs in conscious spontaneously hypertensive rat (SHR). They were the directly intragastric administration of drugs and modified probability sum test for evaluating the synergism of the combination of two drugs., Methods and Results: (1) Directly intragastric administration was used in conscious rats. A catheter was inserted into stomach immediately after arterial catheter insertion. Three days after operation, blood pressure was recorded and drug might be given intragastrically via the gastric catheter. (2) Modified probability sum test was used to evaluate the synergism of two drugs. The formula was: q=P(A+B)/(PA+PB-PAxB). With this method, it was obtained: q=1.32 for the effects of the combination of atenolol and nitrendipine (20 mg/kg+10 mg/kg) on systolic blood pressure; q=1.41 for the effects of the combination of atenolol and amlodipine (10 mg/kg+1 mg/kg) on systolic blood pressure., Conclusion: The two methods introduced by the present work will be important and useful for antihypertensive drug evaluation in conscious freely moving rats.

We and others have demonstrated that impaired arterial baroreceptor reflex (ABR) function is one of the major causes of hypertension-associated end organ damage. The goal of this study was to clarify the potential neuro-humoral mechanisms responsible for impaired ABR-induced end organ damage. The sino-aortic denervated (SAD) rat was used as an animal model of ABR dysfunction. One-week SAD rats were characterized by hypertension, tachycardia, increased norepinephrine content, and decreased beta-endorphin and leu-enkephalin content in hypothalamus and medulla oblongata, and increased plasma levels of arginine-vasopressin. In 18-week SAD rats, the 24-hour average arterial pressure, heart rate, beta-endorphin, and leu-enkephalin content in hypothalamus and medulla oblongata and plasma levels of arginine-vasopressin and angiotensin II were not different from those measured in ABR-intact rats. However, blood pressure variability and angiotensin II content in kidney and left ventricle increased. When exposed to chronic stress, exaggerated changes in arterial pressure, blood pressure variability, the levels of central norepinephrine, beta-endorphin and leu-enkephalin, plasma arginine-vasopressin and angiotensin II, and tissue angiotensin II were found in 18-week SAD rats. These data indicate that a long-term impairment of ABR leads to chronic activation of central noradrenergic neurons and tissue renin-angiotensin system, and that stress induces exaggerated responses of neuro-humoral factors and hemodynamics in SAD rats. Thus, if the present results hold true for humans, one can expect abnormal neurotransmitter/neuromodulator responses to environmental insults in patients with impaired ABR function.

This study was designed to investigate the possible synergism of atenolol and amlodipine on lowering and stabilizing blood pressure (BP) in spontaneously hypertensive rats. Sixty-four spontaneously hypertensive rats were randomly divided into eight groups. They were given 0.8% carboxymethylcellulose sodium (control), atenolol (10 mg/kg), amlodipine (0.5, 1 and 2 mg/kg) and the combinations of atenolol and amlodipine (10 + 0.5, 10 + 1 and 10 + 2 mg/kg), respectively. The drugs were given via a catheter of gastric fistula. BP was recorded for 25 h from 1 h before drug administration to 24 h after administration, in conscious, freely moving rats. It was found that combination of atenolol and amlodipine significantly decreased BP and systolic BP variability. From probability sum analysis it was found that the combination of atenolol and amlodipine, in a proportion as 10 : 1, was the best one (q = 1.54). In conclusion, the present work clearly demonstrated that there is a synergistic effect between atenolol and amlodipine in lowering and stabilizing the BP. The synergistic effect is highest when the dose proportion of the two drugs is 10 : 1.

1. The arterial baroreflex (ABR) plays an important role in the maintenance of the stability of blood pressure. Sinoaortic denervation (SAD) destroys the integrity of the reflex arc and produces severe organ damage in rats. However, partial recovery of ABR function has been observed following chronic denervation. The aim of the present study was to determine whether there was morphological evidence of reinnervation of the aortic arch and carotid sinus following SAD. 2. A substantial body of physiological and morphological evidence suggests that substance P (SP) may be a neurotransmitter contained in first-order sensory baroreceptor afferents; therefore, the patterns of vascular SP and neurofilament (NF) immunoreactive (IR) innervation of the aortic arch and carotid sinus were investigated in the present study. 3. Ten-week-old male Sprague-Dawley rats underwent SAD or sham operation. Whole mounts of carotid bifurcation and aortic arch were prepared for immunohistochemical study at various time points (1, 9 and 16 weeks after operation). 4. The results of computerized image analysis show that the mean density of NF- and SP-IR nerves of SAD rats 9 and 16 weeks after operation increased gradually and significantly compared with that of rats 1 week after operation. 5. In conclusion, the results indicate that there is reinnervation of the aortic arch and carotid sinus by NF- and SP-IR fibres in SAD rats, which may be the morphological basis for the partial restoration of ABR function over time after SAD.

Aim: Angiotensin II and AT1 receptor are the major effector components of renin-angiotensin system (RAS), and also the main growth-stimulating factors in cardiovascular system. The present study was to observe these two factors in the hypertrophied ventricles and aortas of sinoaortic-denervated rats., Methods: Rats were examined at 2, 10, and 16 weeks after sinoaortic denervation (SAD). The hypertrophy was evaluated by the ratio of organ weight to body weight. Angiotensin II concentration and AT1 receptor mRNA expression were measured by radioimmunoassay and RT-PCR respectively, using a positive control of candesartan treatment., Results: Aortic hypertrophy existed in 2-, 10-, and 16-week SAD rats, left ventricular hypertrophy in 10- and 16-week SAD rats, and right ventricular hypertrophy in 16-week SAD rats. In all three kinds of examined SAD rats, plasma angiotensin II levels remained unchanged, indicating circulating RAS is at normal level in the chronic phase of SAD. However, cardiovascular tissue RAS was activated, as evidenced by increase of aortic angiotensin II concentrations at 10 and 16 weeks after SAD, and up-regulation of aortic and left ventricular AT1 receptor mRNA expressions at 16 weeks after SAD., Conclusion: The activated tissue RAS is secondary to the hypertrophy, and probably involved in the maintenance of cardiovascular hypertrophy following SAD.

Aim: To construct an AAV based vector carrying human endothelial nitric-oxide synthase (eNOS) cDNA and study its expression in vitro for future gene therapy., Methods: eNOS cDNA was inserted into the EcoR I site of pSNAV-1 containing the cytomegalovirus (CMV) promoter and inverted terminal repeat sequences of adeno-associated virus. The constructed vector was transfected into BHK and C2C12 cells. eNOS cDNA and mRNA were detected by polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR), respectively., Results: By restriction enzyme digestion analysis, it was proved that eNOS cDNA was inserted into pSNAV-1 in a proper direction. PCR detection demonstrated that pSNAV-eNOS was transferred into both BHK and C2C12 cells. RT-PCR analysis showed that these pSNAV-eNOS transfected cells could express eNOS mRNA., Conclusion: pSNAV-eNOS was successfully constructed with the ability to express human eNOS mRNA in cultured mammalian cells.

Our previous data demonstrate that impairment of arterial baroreceptor reflex (ABR) plays an independent role in hypertension target organ damage. To elucidate the mechanisms responsible for the dysfunction of ABR associated organ damage, sinoaortic denervated (SAD) rats were used as an animal model of ABR dysfunction. Twenty-four-hour continuous blood pressure (SBP and DBP), blood pressure variability (BPV), heart rate (HR) and HR variability (HRV) were measured in conscious and unrestrained rats. Angiotensin II (Ang II) in plasma, heart and kidney was assayed by raio-immunological assay (RIA) 1 or 18 weeks after denervation. In short-term SAD rats, twenty-four-hour mean SBP and DBP increased compared with that of sham-operated rats and long-term SAD rats. No significant difference in SBP, DBP or HR was found between long-term SAD rats and sham-operated ones. Compared with the sham-operated rats, long-term SAD rats had elevated BPV. No significant change in Ang II levels of caridiac and renal tissues was found in short-term SAD rats. In long-term SAD rats, Ang II level of plasma was not increased while the Ang II content in the heart and kidney increased. Ang II contents of plasma and tissues in long-term SAD rats exposed to chronic stress were higher than those in the control rats. These results show (1) in short-term SAD rats blood pressure increased, while in long-term SAD rats 24 h mean blood pressure did not increase, although BPV elevated in long-term SAD rats; (2) in long-term SAD rats, secretion of Ang II in cardiac and renal tissues was enhanced and more Ang II released when the animals were exposed to chronic stress. These results suggest that elevated BPV and secretion of Ang II may be related to the development of organ damage induced by ABR dysfunction.

Aim: To study the importance of reduction of blood pressure variability (BPV) in the organ protection of long-term treatment with combination of nitrendipine and atenolol, which was abbreviated as Nile, in spontaneously hypertensive rats (SHR)., Methods: Combination of nitrendipine (10 mg/kg/d) and atenolol (20 mg/kg/d) was given in SHR chow for 12 weeks. Blood pressure (BP) was then recorded during 24 h in conscious state. After the determination of baroreflex sensitivity (BRS), rats were killed for organ-damage evaluation., Results: Long-term treatment with Nile significantly decreased BP and BPV, ameliorated impaired BRS, and obviously diminished end-organ damage in SHR. The indices of left ventricular and aortic hypertrophy, and glomerulosclerosis score were all positively related to BP and BPV, and negatively related to BRS in untreated and Nile-treated SHR. Multiple-regression analysis showed that decrease in left ventricular and aortic hypertrophy was mainly related to the decrease in systolic BPV, and amelioration in renal lesion was mainly determined by increase in BRS., Conclusion: Long-term treatment with Nile possessed obvious organ protection in SHR. Besides the BP reduction, the decrease in BPV and the restoration of BRS may importantly contribute to this organ protection.

Objective: The main objective was to examine the role of hemodynamics in rat aortic and left ventricular hypertrophy produced by sinoaortic denervation (SAD)., Design and Methods: Rats were examined at different times after SAD or sham operation (Sham). Hemodynamics were recorded continuously in conscious unrestrained rats. The time course of hemodynamic changes and cardiovascular hypertrophy was observed and linear regression analysis was performed to study the role of hemodynamics in SAD-induced aortic and left ventricular hypertrophy. Long-term mortality, water and food intake, and body weight were also determined after operation., Results: High mortality (40%), dramatic reduction of water and food intake, and weight loss occurred within 1 week after SAD. Chronic SAD rats exhibited a marked increase in blood pressure variability (BPV), with no change in the average level of blood pressure (BP), as compared with the Sham control rats. Increased BPV was higher at 2 weeks (about threefold) than 16 weeks (about twofold) after SAD. Aortic hypertrophy existed in all three kinds of examined rats: 2-, 10- and 16-week SAD rats. Left ventricular hypertrophy was found only in 10- and 16-week SAD rats. Both aortic hypertrophy and left ventricular hypertrophy were significantly and positively correlated with BPV, but not with BP level., Conclusion: Persistent high BPV following SAD can lead to aortic and left ventricular hypertrophy. The aorta is more sensitive to increased BPV than the heart.

Aim: To study the effect of candesartan cilexetil (candesartan), a new AT1 receptor antagonist, on sinoaortic denervation (SAD)-induced cardiovascular hypertrophy and its potential mechanisms in rats., Methods: For long-term treatment, candesartan (6 mg/kg/d) was given in rat food for 16 weeks after SAD surgery, and for acute treatment, a single dose of candesartan (3 mg/kg) was administrated intragastrically at 30 d after SAD., Results: The indexes of left ventricular and aortic hypertrophy in candesartan-treated SAD rats were decreased when compared with untreated SAD rats, and similar to or less than those in normal rats. SAD-induced cardiomyocyte hypertrophy, myocardial fibrosis, wall thickening of intramyocardial arterioles and aortae, and destruction of vascular internal elastin membrane were almost inhibited by candesartan. The plasma angiotensin II levels were markedly increased in treated SAD rats and negatively correlated with the indexes of hypertrophy. Both blood pressure and its variability were reduced by a single dose of candesartan during 3 h of observation period., Conclusion: Candesartan can efficiently inhibit SAD-induced cardiovascular hypertrophy. In addition to known mechanisms, upregulation of circulating angiotensin II and stabilization of blood pressure may be involved in this cardiovascular protection of candesartan.

Arterial baroreflex (ABR) is a very important mechanism in the regulation of cardiovascular activities. As ABR function is largely inhibited by anesthesia, its measurement in conscious animal becomes important. The present review summarizes the works concerning ABR function in conscious rats completed in our department in the last 10 years. Firstly, a new method was established to measure arterial baroreflex-blood pressure control (ABR-BP). ABR-BP and baroreflex sensitivity measured with classic method are two different parts of the ABR function. Secondly, it was proposed that ABR function predicted the end-organ damage in hypertension. Thirdly, interruption of ABR induced severe end-organ damages. Increased blood pressure variability (BPV) and activation of renin angiotensin system were involved in the mechanisms underlying organ damages in sinoaortic denervation (SAD) rats. Fourthly, we propose that amelioration of ABR function may serve as a new strategy for improving the prognosis of cardiovascular diseases. Ketanserin improved the impaired ABR function in SHR. Finally, the possibility to develop a strain of rats with spontaneous deficiency on ABR function is mentioned.

Aim: To study the determination of arterial baroreflex-blood pressure control (ABR-BP) in conscious rats., Methods: Blood pressure was continuously recorded with a computerized system in conscious freely moving rats. The principle of ABR-BP measurement is to compare the pressor response to a vasoactive drug (angiotensin II) before and after the interruption of this reflex., Results: (1) ABR-BP values revealed by angiotensin II were closely correlated with those by phenylephrine. Doses of angiotensin II did not influence the results within certain range. (2) ABR-BP was well correlated with arterial baroreflex-heart period control (ABR-HP). (3) Anesthesia inhibited ABR-BP. There existed a circadian variation of ABR-BP in WKY rats. (4) Blood pressure variability was closely related to ABR-BP, but not to ABR-HP. (5) ABR-BP was impaired in hypertensive rats., Conclusion: ABR-BP is an important parameter to reflect the function of ABR. The present work makes it possible to determine ABR-BP in conscious rats. ABR-BP plays an important role in maintaining blood pressure stability and it is impaired in hypertension.