Biomedical subjects

Ding-Feng Su

Publications and source records attributed to Ding-Feng Su.

At least 19 recordsLinked to original sources

PubMed2006

Blood pressure variability, baroreflex sensitivity and organ damage in spontaneously hypertensive rats treated with various antihypertensive drugs.

Besides blood pressure, blood pressure variability and baroreflex sensitivity maybe important factors determining organ damage in hypertension. This study was designed to investigate the effects of various antihypertensive drugs on blood pressure and blood pressure variability reductions, baroreflex sensitivity, and target organ damage in spontaneously hypertensive rats (SHR). The dose is 20 mg/kg/day for atenolol, and 10 mg/kg/day for nifedipine, irbesartan and hydrochlorothiazide. We used relatively low doses of drugs to avoid a very remarkable normalization of blood pressure in the treatment, which would make it much difficult to distinguish the contribution of blood pressure variability and baroreflex sensitivity to organ protection from that of blood pressure. Drugs at the aforementioned doses were mixed into rat chow. SHR were treated for 4 months. Blood pressure was then continuously recorded for 24 h. After the determination of baroreflex sensitivity, rats were killed for organ-damage evaluation. It was found that long-term treatment with atenolol, nifedipine, irbesartan or hydrochlorothiazide all markedly reduced blood pressure variability, enhanced baroreflex sensitivity, and produced significant organ protection. Compared with blood pressure level, blood pressure variability and baroreflex sensitivity values showed a much closer or similar relationship with organ-damage parameters in every treatment group of rats. Multiple-regression analysis showed that the decrease in left ventricular hypertrophy, the decrease in aortic hypertrophy and the amelioration in renal lesion were all most closely correlated with the increase in baroreflex sensitivity and the decrease in systolic blood pressure variability. In conclusion, long-term treatment with atenolol, nifedipine, irbesartan or hydrochlorothiazide produced organ protection in SHR. Besides the blood pressure reduction, the decrease in blood pressure variability and the restoration of baroreflex sensitivity may contribute to this organ protection.

Animals↗

PubMed2006

Functional arterial baroreflex attenuates the effects of antihypertensive drugs in conscious rats.

The present work was designed to observe the influences of arterial baroreflex (ABR) function on cardiovascular effects produced by four routinely used antihypertensive drugs in conscious rats. A low ABR model was obtained by the performance of sinoaortic denervation (SAD). The doses of the four drugs were as follows: nifedipine (1.5, 3.0 mg/kg), captopril (50, 100 mg/kg), atenolol (10, 20 mg/kg), and hydrochlorothiazide (20, 40 mg/kg). They were administered via an intra-gastric catheter. Compared with sham-operated rats, SAD significantly increased blood pressure variability about 2 times without modification of blood pressure level. The decrease in blood pressure level induced by the four tested drugs was larger in SAD rats than in sham-operated rats, which decreased to about 10 mmHg. Pulse interval was not changed by the treatment of captopril, but prolonged by atenolol in both sham-operated and SAD rats. In sham-operated groups, treatment of both nifedipine and hydrochlorothiazide decreased pulse interval. Whereas in sinoaortic denervated ones, this tachycardia was prevented. Among the four tested drugs, it was found that only nifedipine and atenolol significantly decreased blood pressure variability in SAD rats. It can be concluded that arterial baroreflex function was able to attenuate the hypotensive effects produced by antihypertensive drugs in conscious rats.

Animals↗

PubMed2006

Treatment of hypertension based on measurement of blood pressure variability: lessons from animal studies.

PURPOSE OF REVIEW: Blood pressure variability, a quantitative index for the spontaneous variation in blood pressure, has been proposed as a risk factor for end-organ damage and to determine the efficacy of hypertension treatment. RECENT FINDINGS: Animal studies indicate that blood pressure variability is as important as blood pressure level in determining end-organ damage, and that high blood pressure variability is associated with end-organ damage, including myocardial lesions, aortic hypertrophy, vascular remodeling and renal damage. Although the organ damage induced by high blood pressure variability was similar to that induced by hypertension, comparative studies in sinoaortic-denervated and spontaneously hypertensive rats revealed that aortic hypertrophy is a sensitive index of high blood pressure variability, and left ventricular hypertrophy is a sensitive index of high blood pressure level. The possible mechanisms for high blood pressure variability-induced end-organ damage include: direct endothelial lesions, renin-angiotensin system activation, inflammation initiation and cardiomyocyte apoptosis augmentation. Blood pressure variability reduction contributes importantly to the organ-protective effect of some antihypertensive drugs. SUMMARY: Although animal studies suggest some advantages in blood pressure variability measurements, clinical trials are necessary before the widespread use of blood pressure variability as a predictor of hypertensive organ damage and a new strategy for the treatment of hypertension.

Animals↗

PubMed2006

Blood pressure variability is more important than blood pressure level in determination of end-organ damage in rats.

OBJECTIVE: This study was designed to determine how important a novel risk factor of elevated blood pressure variability (BPV) is in the determination of end-organ damage by comparison with the classic risk factor of a high blood pressure (BP) level. METHODS AND RESULTS: The effects of haemodynamics on cardiovascular morphology were evaluated by univariate and multivariate regression analysis in two different rat models with an enlarged distribution of haemodynamics. In male sham-operated and sinoaortic-denervated Wistar-Kyoto rats and spontaneously hypertensive rats (n = 34), BPV was more important than BP in cardiac and renal damage and aortic hypertrophy. BPV and BP had independent effects, explaining 59.4% of the variation in damage to these organs. In male (n = 44) and female (n = 46) F1 hybrids of Sprague-Dawley rats and spontaneously hypertensive rats, the greater importance of BPV than BP was further demonstrated in left ventricular hypertrophy, glomerular damage and aortic hypertrophy. The phenomenon was more evident in females than males for cardiovascular hypertrophy. BPV and BP or BPV alone had independent effects, explaining 46.9% (male) or 37.5% (female) of the variation in damage to these organs. CONCLUSION: BPV is a more critical determinant than BP level for cardiac damage, renal lesions and aortic hypertrophy in rats, strongly suggesting the significance of BPV control for the protection of these organs.

Animals↗

PubMed2006

Early structural changes of aortic wall in sinoaortic-denervated 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.

Animals↗

PubMed2006

Arterial baroreflex is not involved in salt preference in 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.

Animals↗

PubMed2006

Effects of nine antihypertensive drugs on blood pressure variability in sinoaortic-denervated rats.

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.

Animals↗

PubMed2006

In vivo and in vitro evaluation of essential oils from Ligusticum chuanxiong Hort on the transdermal delivery of flurbiprofen in rabbits.

The present study was designed to evaluate skin permeation enhancement effect of essential oils from Ligusticum chuanxiong Hort (chuanxiong oil) in rabbits and to compare the in vivo absorption and in vitro permeation using flurbiprofen as a model drug. In vivo results demonstrated that chuanxiong oil showed a rapid and marked permeation enhancement effect. The group with 10% oil exhibited the highest value of area under the curve (AUC) of 418+/-124 microg/ml x h, which was 2.43 times the high of control. The AUC value of 3% oil group (245+/-81.6 microg/ml x h) was similar to that of 5% oleic acid group (235+/-74.5 microg/ml x h). Whereas in vitro results indicated the enhancement of chuanxiong oil was relatively weak. The group with 3% oil appeared to the highest flurbiprofen flux (84.9+/-19.3 microg/cm2/h), to some extent lower than 5% oleic acid group (107+/-5.85 microg/cm2/h). At 10% and 15% concentrations, chuanxiong oil even decreased the flux of flurbiprofen compared with the control. Both in vitro results with pretreated skin and flurbiprofen content accumulated in skin indicated the potential mechanism for the in vitro enhancement of chuanxiong oil was the weakened barrier function by improving in the partitioning of flurbiprofen to the stratum corneum. The discrepancy was noted between the in vivo and in vitro results, indicating only about the weakened barrier function was not enough to explain the sharply increment of in vivo absorption of flurbiprofen by chuanxiong oil. The GS-MS results indicated phthalides identified from chuanxiong oil might mainly contribute to enhance in vivo absorption of flurbiprofen because of its large quantities (91.15%).

Acrylic Resins↗

PubMed2005

Action site of ketanserin enhancing baroreflex function is within the rostral ventrolateral medulla in anesthetized rats.

In our previous studies, it was found that ketanserin enhanced baroreflex sensitivity (BRS) in rats and this effect was not blood pressure dependent. The present work was designed to investigate the effects of ketanserin on BRS within the nucleus tractus solitarus (NTS) and the rostral ventrolateral medulla (RVLM). In anesthetized rats, BRS were evaluated by the changes in depressor action of aortic nerve stimulation and bradycardiac response to rapid pressor action of intravenous phenylephrine. It was found that bilateral injection of ketanserin (250 pmol for each side) into the NTS not only significantly increased blood pressure, but also attenuated baroreflex function. Interestingly, when ketanserin was bilaterally injected into RVLM, a significant enhancement of BRS was found and there were no modifications in basal blood pressure and heart period. The present study demonstrates that ketanserin-induced enhancement of BRS mainly occurred within the RVLM, which might contribute to the systemic effects of ketanserin on BRS.

Adrenergic alpha-Agonists↗

PubMed2005

Effects of long-term treatment with candesartan on hemodynamics and organ damage in spontaneously hypertensive rats.

UNLABELLED: This study was designed to investigate the effects of candesartan on blood pressure (BP) and blood pressure variability (BPV) reductions, baroreflex sensitivity (BRS) amelioration, and organ protection in spontaneously hypertensive rats (SHR). METHODS: Studies were performed in two groups of SHR (n = 13 for control rats; and n = 20 for candesartan-treated rats) and one group of WKY rats (n = 13). Candesartan (3 mg /kg/d) was given in rat chow for 4 months. BP was then continuously recorded for 24 hours in conscious state. After the determination of BRS, rats were killed for organ-damage evaluation. RESULTS: Long-term treatment with candesartan significantly reduced BP and BPV expressed by both standard deviation and variation coefficient of BP, enhanced BRS and produced obvious organ protection. Compared with BP level, BPV and BRS values showed a closer or similar relationship with organ-damage parameters in SHR. Multiple regression analysis showed that the decrease in left ventricular hypertrophy was most closely associated with the increase in BRS, whereas the decrease in aortic hypertrophy was most closely associated with the decrease in 24-hour systolic BPV, and the amelioration in renal lesions, with the increase in BRS and the decrease in 24-hour systolic BPV. CONCLUSION: long-term treatment with candesartan results in organ protection in SHR. Besides BP reduction, the decrease in BPV and the restoration of BRS are significantly related to this organ protection.

Administration, Oral↗

PubMed2005

Arterial baroreflex dysfunction promotes atherosclerosis in rats.

The present study was designed to test the hypothesis that arterial baroreflex dysfunction promotes the development of atherosclerosis. Experiment 1: the baroreflex sensitivity (BRS) was measured in 30 Sprague-Dawley (SD) rats in conscious state with a computerized blood pressure monitoring system. Four weeks later, the rats were administered with Vitamin D3, and fed with the high-cholesterol diet for 8 weeks to induce atherosclerosis. The hearts and aortae were removed for pathological examination. A negative correlation was found between BRS and the scores of coronary (r=-0.464, P<0.01) or aortic atherosclerosis (r=-0.524, P<0.01) in SD rats. Experiment 2: sinoaortic denervation (SAD) was performed in SD rats. Then atherosclerosis was also induced. The atherosclerosis scores in SAD rats were significantly higher than those in sham-operated rats (aortic score: 1.50+/-0.41 versus 1.10+/-0.39, P<0.05; coronary score: 1.70+/-0.35 versus 1.25+/-0.54, P<0.05). Using immunohistochemistry and Western blotting methods, it was found that the expressions of C-reactive protein, intercellular adhesion molecule-1 and vascular-cell adhesion molecule-1 in coronary artery and aorta were increased in SAD rats compared with sham-operated rats. These results indicate that arterial baroreflex dysfunction promotes the development of atherosclerosis in rats, and that inflammation may be involved in this process.

Animals↗

PubMed2005

Reduction of blood pressure variability: a new strategy for the treatment of hypertension.

The main aims of the treatment of hypertension are to prevent end-organ damage (EOD) and to avoid consequent lethal complications associated with hypertension. Blood pressure level is a well-known determinant of EOD. However, recent studies suggest that blood pressure variability (BPV) is as important as blood pressure level in determining EOD. The reduction of BPV is an important contributory factor of the organ protection provided by some antihypertensive drugs. Thus, reduction of BPV might represent a new strategy for the treatment of hypertension.

Animals↗

PubMed2005

Effects of low-dose ketanserin on blood pressure variability, baroreflex sensitivity and end-organ damage in spontaneously hypertensive rats.

The present study was designed to investigate the effects of low-dose ketanserin on BPV (blood pressure variability), BRS (baroreflex sensitivity) and organ damage in SHR (spontaneously hypertensive rats). Ketanserin was mixed in rat chow at an estimated dose of 0.1 mg.kg(-1) of body weight.day(-1). SHR were treated for 4 months. BP (blood pressure) was then recorded continuously for 24 h in a conscious state. After determination of BRS, rats were killed for organ damage evaluation. It was found that long-term treatment with low-dose ketanserin did not lower BP levels, but significantly decreased BPV, enhanced BRS and reduced organ damage in SHR. Multiple regression analysis showed that the decrease in left ventricular hypertrophy was most closely correlated (or associated) with the increase in BRS, whereas the decrease in aortic hypertrophy was most closely associated with the decrease in diastolic BPV and the amelioration in renal lesion, with the increase in BRS and the decrease in diastolic BPV. In conclusion, low-dose ketanserin produces organ protection independently of its BP-lowering action in SHR, and this organ protection was importantly attributable to the enhancement of BRS and decrease in BPV.

Animals↗

PubMed2005

Synergism of atenolol and nitrendipine on hemodynamic amelioration and organ protection in hypertensive rats.

OBJECTIVE: This study was designed to investigate the possible synergism of atenolol and nitrendipine on blood pressure (BP) and blood pressure variability (BPV) reductions, baroreflex sensitivity (BRS) amelioration, and organ protection in hypertensive rats. METHOD: The dose was 20 mg/kg for atenolol, 10 mg/kg for nitrendipine and 20 + 10 mg/kg for the combination of these two drugs. In an acute study, a single dose was given via a catheter previously inserted into the stomach in spontaneously hypertensive rats (SHR). In a subacute study, SHR, deoxycorticosterone acetate (DOCA)-salt rats, and two-kidney, one-clip (2K1C) rats were used. They received the same dose by gavage daily for 10 days. BP was measured 24 h after drug administration. In chronic studies, these drugs at the aforementioned dose were mixed into rat chow. SHR were treated for 4 months. BP was then continuously recorded for 24 h. After the determination of BRS, rats were killed for organ-damage evaluation. RESULTS: In the acute study, it was found that the combination of atenolol and nitrendipine had an obviously greater and longer BP reduction than treatment with each of these two drugs separately. In the subacute study, an effective decrease in BP 24 h after administration was found only in the rats treated with the combination. In chronic studies, it was found that the combination possessed the obvious synergism on BP and BPV reduction, BRS amelioration and organ protection in SHR. Multiple-regression analysis showed that the decrease in left ventricular hypertrophy was most significantly related to the decrease in systolic BPV and BP, the decrease in aortic hypertrophy was most significantly related to the increase in BRS and the decrease in systolic BPV, and amelioration in the renal lesion was most significantly associated with the restoration of BRS. CONCLUSION: Treatment with a combination of atenolol and nitrendipine exhibited a rapid and persistent antihypertensive effect and possessed an obvious synergism on BP and BPV reduction, BRS restoration and organ protection in hypertensive rats. The decrease in BPV and the restoration of BRS may importantly contribute to organ protection in SHR with chronic treatment.

Animals↗

PubMed2005

Diminished responses to nifedipine imply severe end-organ damage in spontaneously hypertensive rats.

This study was designed to investigate the effect of end-organ damage (EOD), the initial blood pressure levels, and baroreflex sensitivity (BRS) on the blood pressure-lowering effect of nifedipine in spontaneously hypertensive rats (SHRs). Nifedipine was intravenously administered at a dose of 1 mg/kg. BP was continuously recorded in the conscious state before and after nifedipine administration. BRS was determined before drug administration. Two days after the blood pressure (BP) recording, rats were killed for organ-damage evaluation. Univariate correlation analysis showed that BP changes induced by nifedipine injection were negatively correlated with EOD score and aortic weight/length but positively correlated with left kidney weight/body weight and basal BP levels. Stepwise multiple linear regression analysis demonstrated that increase in overall end-organ damage was most significantly related to the decrease in hypotensive effect of nifedipine; increase in aortic hypertrophy was also related to a decreased fall in systolic and diastolic BP induced by nifedipine, whereas increase in initial BP levels was associated with increased hypotensive effect of nifedipine. In conclusion, the severity of overall EOD contributed more than basal BP levels to the diminished responses to nifedipine, and aortic hypertrophy was also involved in diminished drug responses.

Animals↗

PubMed2005

Blood pressure variability, cardiac baroreflex sensitivity and organ damage in experimentally hypertensive rats.

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.

Angiotensin II↗

PubMed2004

Electrophysiological evidences for the contribution of NMDA receptors to the inhibition of clonidine on the RVLM presympathetic neurons.

The main objective of this study is to test the hypothesis that N-methyl-D-aspartate (NMDA) receptors within the rostral ventrolateral medulla (RVLM) are involved in the inhibition of clonidine on the RVLM presympathetic neurons. Totally, 22 presympathetic neurons were recorded in anesthetized and paralyzed rats. The majority of these neurons (n=16 of 22) were significantly inhibited by iontophoretic (30 nA) clonidine, the other 6 neurons were insensitive to clonidine. In seven clonidine-sensitive neurons, iontophoretic clonidine (30 nA) antagonized the neuronal excitation of iontophoretic NMDA receptor agonist NMDA (20 nA). In remaining nine clonidine-sensitive neurons, iontophoretic NMDA receptor antagonist MK801 (60 nA) significantly attenuated the neuronal inhibition of iontophoretic (30 nA) clonidine. In conclusion, these results suggest that NMDA receptors contribute to the inhibition of clonidine on the RVLM presympathetic neurons.

Action Potentials↗

PubMed2004

Cardiovascular effects of agmatine within the rostral ventrolateral medulla are similar to those of clonidine in anesthetized rats.

Agmatine was isolated from bovine brain in 1994. It exhibits various functions, as a consequence of which it meets the criteria for an endogenous brain neurotransmitter. However, its physiological action on the cardiovascular system remains unclear. This study was designed to clarify its cardiovascular effects when administered into the rostral ventrolateral medulla (RVLM) in anesthetized and paralyzed rats. Unilateral injection of clonidine (5 nmol) into the RVLM significantly decreased mean arterial pressure (MAP) and heart rate (HR). Unilateral injection of agmatine (5 nmol) produced similar effects to clonidine. The amplitude of the decrease in HR was the same as with clonidine, but the amplitude of the decrease in MAP was less pronounced. The cardiovascular inhibition induced by clonidine (5 nmol) and agmatine was abolished by idazoxan (5 nmol). Similar to clonidine, agmatine inhibited the pressor effect of L-glutamate (2 nmol) injected into the RVLM. The duration of this effect (about 6 min) was shorter than that observed with clonidine (about 12 min). Bilateral injection of agmatine into the RVLM inhibited the depressor response induced by baroreflex activation (electrical stimulation of the aortic nerve), and this effect was similar to, but less pronounced than, that induced by clonidine. Idazoxan (5 nmol) antagonized the cardiovascular effects of clonidine and agmatine within the RVLM. However, it produced a similar effect to clonidine injected into the RVLM. It is concluded that agmatine exerts a similar cardiovascular effect to clonidine, with less potency within the RVLM. Idazoxan might be a partial agonist for imidazoline I(1) receptors.

Adrenergic alpha-Agonists↗