Biomedical subjects

Ding-Feng Su

Publications and source records attributed to Ding-Feng Su.

50 records · Page 3Linked to original sources

PubMed2003

Inflammation is involved in the organ damage induced by sinoaortic denervation in rats.

OBJECTIVE: The present study was designed to test the hypothesis that inflammation is involved in the end-organ damage (EOD) induced by sinoaortic denervation (SAD) in rats. METHOD: SAD was performed in male Sprague-Dawley rats at the age of 10 weeks. Under anaesthesia, aortic nerves were cut and the sinus region of the carotid artery was stripped and painted with 10% phenol. Pathological evaluation of EOD and the determination of plasma or tissue levels of the factors related to inflammation, including thromboxane B2 (TXB2) interleukin-1 (IL-1), tumour necrosis factor alpha (TNF-alpha) and reactive oxygen species (ROS) were performed at 16 weeks after SAD. Pathological evaluation of EOD included heart weight ratio, myocardial and blood vessel hydroxyproline and collagen volume fraction, glomerular injury score and number of infiltrating inflammatory cells. Indomethacin (20 mg/kg per day, orally) or vitamin E (100 mg/kg per day, orally) was administered for 12 weeks, beginning from 4 weeks after SAD, to observe their effects on SAD-induced EOD. RESULTS: There were significant fibrosis and inflammatory infiltration in the myocardium and blood vessels, represented by higher hydroxyproline and collagen volume fraction, and a large amount of inflammatory cells in the tissues of SAD rats. Heart weight and kidney glomerular injury score were significantly higher in SAD than in sham-operated rats. Plasma TXB2, TNF-alpha, IL-1 and tissue ROS increased significantly after SAD. Indomethacin and vitamin E significantly decreased the contents of some factors related to inflammation in SAD rats. Both drugs also alleviated myocardial and vessel fibrosis, inflammatory infiltration and kidney damage. CONCLUSION: Inflammation is involved in the organ damage induced by SAD in rats.

Animals↗

PubMed2003

Effects of long-term treatment with ketanserin on blood pressure variability and end-organ damage in spontaneously hypertensive rats.

It has been proposed that instability of blood pressure may produce organ damage. Ketanserin is an anti-hypertensive drug with an ability to reduce blood pressure variability (BPV) in acute experiments in spontaneously hypertensive rats (SHRs). The present work was designed to observe the effects of long-term treatment with ketanserin on BPV and end-organ damage in SHRs. Ketanserin was mixed in rat chow at an estimated dose of 10 mg/kg/d. After 5 months of drug administration, BP was continuously recorded in conscious, freely moving rats for 24 h. The heart, kidneys, and abdominal aorta were then isolated and examined by using histologic methods and computer image analysis. In another work, the effects of hydralazine (40 mg/kg/d, for 5 months) on BP, BPV, and organ damage were observed in SHRs. Ketanserin significantly decreased BP and BPV, ameliorated impaired arterial baroreflex function, and significantly prevented the target organs of SHRs from being damaged. This preventive effect was characterized by decrease in left ventricular hypertrophy, diminution of glomerulus damage, and amelioration in vascular lesion. Hydralazine decreased BP but did not lower BPV. No organ protection was found in hydralazine-treated rats. In conclusion, long-term treatment with ketanserin reduced hypertensive organ damage. Lowering BP, decreasing BPV, and ameliorating arterial baroreflex function may contribute together to this effect.

Animals↗

PubMed2003

Effects of long-term treatment with candesartan on organ damages in sinoaortic denervated rats.

The study was designed to observe the effects of long-term treatment with candesartan cilexetil (candesartan) on blood pressure (BP), blood pressure variability (BPV), baroreflex sensitivity (BRS) and end-organ damage (EOD) in sinoaortic denervated (SAD) rats. Candesartan was mixed in rat chow at an estimated dose of 3 mg/kg/day. After 12 weeks of drug administration, rats were instrumented to determine BP, BPV and BRS in conscious state. Organ damage was estimated by observation of morphologic changes. When compared with sham-operated rats, SAD rats exhibited increased BPV, decreased BRS, and normal BP and plasma angiotensin II level. Left ventricular and aortic hypertrophies and renal lesion were found in SAD rats. Candesartan significantly decreased BP and BPV, ameliorated impaired BRS, increased plasma angiotensin II level and obviously diminished the EOD in SAD rats. Multiple-regression analysis shows that decrease in left ventricular hypertrophy was mainly related to decrease in systolic BPV. Decrease in aortic hypertrophy was mainly determined by increase in BRS and decrease in systolic BP. Amelioration in renal lesion was predicted by increase in BRS and decrease in systolic BPV. BRS was the most important determinant for renal lesion and aortic hypertrophy in SAD rats. In addition, plasma angiotensin II level was higher in candesartan-treated rats. In conclusion, long-term treatment with candesartan prevented SAD-induced organ damage. Restoration of arterial baroreflex function, decrease in BPV, and blockade of activated renin-angiotensin system may contribute to the organ protective action of candesartan in SAD rats.

Animals↗

PubMed2003

Role of I1-imidazoline receptors within the caudal ventrolateral medulla in cardiovascular responses to clonidine in rats.

Although it is recognized that imidazoline receptors play an important role in the central regulation of cardiovascular activities, little is known about their role in the caudal ventrolateral medulla. In male Sprague-Dawley rats anesthetized with urethane, we used antagonists of I1-imidazoline receptor or alpha2-adrenoceptor to assess the function of these receptors in the caudal ventrolateral medulla in controlling the cardiovascular effects of clonidine. Unilateral microinjection of clonidine (6 nmol/50 nl) into the caudal ventrolateral medulla significantly (P<0.01) increased blood pressure and the discharge of the rostral ventrolateral medulla presympathetic neurons, while heart rate remained unchanged. Microinjection of yohimbine (a selective alpha2-adrenoceptor antagonist, 500 pmol/50 nl) into the caudal ventrolateral medulla did not modify blood pressure, heart rate, or the discharge of the rostral ventrolateral medulla presympathetic neurons, and failed to attenuate the local caudal ventrolateral medulla clonidine-induced blood pressure elevation. However, unilateral microinjection of idazoxan (a mixed antagonist of imidazoline receptor and alpha2-adrenoceptor, 2 nmol/50 nl) into the caudal ventrolateral medulla significantly (P<0.01) decreased mean arterial pressure, heart rate, and the discharge of the rostral ventrolateral medulla presympathetic neurons, and completely abolished the pressor effect of clonidine. In addition, bilateral microinjection of idazoxan (4 nmol in 100 nl for each side) into the caudal ventrolateral medulla effectively (P<0.01) blocked the depressor effects of clonidine administered intravenously (5 and 50 microg/kg). These results confirm that I1-imidazoline receptors within the caudal ventrolateral medulla are involved in maintaining the tonic cardiovascular activities and in the pressor effect of clonidine in the caudal ventrolateral medulla. In addition, it seems that the caudal ventrolateral medulla plays an important role in the antihypertensive effects of systemically administered clonidine in rats.

Action Potentials↗

PubMed2003

Morphological evidence of reinnervation of the baroreceptive regions in sinoaortic-denervated rats.

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.

Animals↗

PubMed2003

Construction of a recombinant vector based on AAV carrying human endothelial nitric-oxide synthase gene.

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.

Animals↗

PubMed2003

Angiotensin II and AT1 receptor in hypertrophied ventricles and aortas of sinoaortic-denervated rats.

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.

Angiotensin II↗

PubMed2002

The importance of blood pressure variability in rat aortic and left ventricular hypertrophy produced by sinoaortic denervation.

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.

Animals↗

PubMed2002

Determination of arterial baroreflex-blood pressure control in conscious rats.

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.

Angiotensin II↗

PubMed2002

Arterial baroreflex function in conscious rats.

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.

Animals↗

PubMed2002

Candesartan inhibits sinoaortic denervation-induced cardiovascular hypertrophy in rats.

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.

Angiotensin Receptor Antagonists↗

PubMed2002

Importance of blood pressure variability in organ protection in spontaneously hypertensive rats treated with combination of nitrendipine and atenolol.

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.

Animals↗

PubMedDate not supplied

Restoration of arterial baroreflex function contributes to organ protection in spontaneously hypertensive rats treated with long-term hydrochlorothiazide mixture.

1. Hydrochlorothiazide mixture (HCTM) is widely used in China for the treatment of hypertension. This mixture consists of hydrochlorothiazide, triamterene, reserpine, hydralazine and chlordiazpoxide, with small (one-third to one-fifth of normal) doses of each drug. The present study was designed to investigate the effects of this mixture on blood pressure, blood pressure variability (BPV), baroreflex sensitivity (BRS) and end-organ damage in spontaneously hypertensive rats (SHR). 2. The HCTM was mixed in the rat chow and rats were treated for 4 months. After treatment, rats were catheterized and their blood pressure, BPV and BRS were measured in the conscious state. Organ damage was examined after these measurements had been completed. 3. It was found that HCTM not only decreased blood pressure and BPV, but also ameliorated impaired BRS in SHR. The HCTM had an obvious effect on organ protection in SHR. 4. The HCTM prevented left ventricular hypertrophy and this effect was mainly related to a decrease in systolic blood pressure. The effects of HCTM on preventing renal atrophy were mainly determined by BRS. Baroreflex sensitivity was the most important determinant for predicting organ damage in HCTM-treated SHR. 5. In conclusion, long-term treatment of rats with HCTM prevented hypertensive organ damage. Restoration of arterial baroreflex function contributes to organ protection in SHR treated in the long term with HCTM.

Animals↗

PubMedDate not supplied

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.

Animals↗