[New concept of cardiovasology: vascular remodeling].
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Biomedical subjects
Publications and source records attributed to D F Su.
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The effects of silybin and tetrandrine on the survival of spontaneously hypertensive rats subjected to acute coronary artery occlusion were investigated. The mortality after acute coronary occlusion in spontaneously hypertensive rats (66.7%) was higher than that of control Wistar-Kyoto rats (20%, P < 0.05). Oral administration of silybin (300 mg/kg daily) for 8-12 days reduced mortality in spontaneously hypertensive rats (0, P < 0.01 in comparison with untreated spontaneously hypertensive rats). Administration of tetrandrine 40 mg/kg daily for 8-12 days reduced the mortality to some extent (22.2%, P = 0.051, as compared with control rats). Silybin reduced blood pressure and the incidence of post-occlusion arrhythmias in spontaneously hypertensive rats to the same extent as tetrandrine. Both silybin and tetrandrine decreased the severity of ventricular hypertrophy. Although there were significant decreases in risk zone and infarct zone in silybin- and tetrandrine-treated rats, the ratio of infarct to risk zone was not changed. The results implies that silybin may be beneficial when used in hypertensive patients who develop acute myocardial infarction.
The effects of ketanserin on blood pressure and heart rate were studied in sinoaortic denervated (SAD) rats. It was found that the dose-effect curves for blood pressure and heart rate were the same in anesthetized SAD and sham-operated rats. However, SAD sharpened the dose-effect curves in conscious freely moving rats. It is concluded that the lack of hypotensive effect of ketanserin in conscious normotensive animals is due in large part to the integrity of the arterial baroreflex.
1. The short-term (within 30 min periods) and the long-term (among 30 min periods) variabilities, expressed as variation coefficients, of blood pressure (BP) and heart period (HP) were studied using a computer analysis of BP recordings in freely moving genetically hypertensive (LH), normotensive (LN) and low BP (LL) rats of Lyon strains at ages 5, 9, 21 and 40 weeks. The baroreflex control of HP was estimated with the slope of the linear relationship between systolic BP (SBP) and HP (SBP-HP slope) computed after phenylephrine and nitroglycerin injections. 2. Short-term variability of BP increased between 5 and 9 weeks of age and then remained stable. Hypertension was accompanied by an increase in both short- and long-term variabilities of diastolic BP in adult rats. 3. A sharp increase in SBP-HP slope was observed between 5 and 9 weeks of age in LN rats. SBP-HP slope of LH rats increased slightly up to 21 weeks but remained lower than that of normotensive controls. 4. The weak inverse correlation existing between SBP-HP slope and BP variability appeared to be mediated by the BP level. In addition, atropine which is known to abolish almost completely the SBP-HP slope, did not increase BP variability. It is concluded that SBP-HP slope is not linearly associated with BP variability in conscious rats.
1. Intra-aortic blood pressure was recorded continuously in freely moving genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) rats of the Lyon strain during two 11 h periods (08:00-19:00 h). During the first period (control), the animals were left undisturbed and during the second period (stress), a jet of air was applied for 20 min every hour. Urine was collected simultaneously and analysed for its content in norepinephrine and epinephrine. 2. The first exposure to the stressor induced larger increases in blood pressure and heart rate in LH than in LN and LL rats. However blood pressure and heart rate responses to the 10 following stressors decreased in LH rats while they remained stable in LN and LL animals. 3. Repeated stress exposure induced significant increases in epinephrine excretion in both LN and LL but not in LH rats. 4. It is concluded that LH rats exhibit marked cardiovascular habituation to repeated stress. Taken together with the lack of stress-induced sympathoadrenal activation, this suggests a reduced level of emotional responsiveness in Lyon hypertensive rats.
The antihypertensive effects of atenolol (Ate) or nitrendipine (Nit) alone or in combination (Ate+Nit) were studied in conscious experimental hypertensive rats. The hypotensive effects of single ig of Ate 20 + Nit 10 mg.kg-1 were rapid and persistent in spontaneously hypertensive rats (SHR). In renovascular hypertensive rats (RVHR) and DOCA-salt hypertensive rats (DHR), Ate+Nit (6 + 3, 20 + 10, 60 + 30 mg.kg-1) given ig once a day for 10 d reduced the blood pressure in a dose-dependent manner. But Ate 20 mg.kg-1 or Nit 10 mg.kg-1 alone given ig once a day for 10 d caused no obvious reduction in blood pressure in RVHR, DHR, and SHR q = 1.32. These results revealed that the synergy is present in the antihypertensive action of Ate+Nit.
The effect of ketanserin on arterial baroreflex-blood pressure control (ABR-BP) were studied in conscious freely-moving spontaneously hypertensive rats (SHR) and renovascular hypertensive rats (RVHR). The ABR-BP was measured by using a new method comparing with the pressor responses (in area) to angiotensin II before and after blocking the baroreflex efferent pathway by guanethidine and methyl atropine. It was found that ketanserin enhanced markedly the ABR-BP in both groups of hypertensive rats (SHR: 51% to 74%; RVHR: 59% to 77%). This suggests that the enhancement of ABR-BP may be involved in the anti-hypertensive effects of ketanserin.
Computerized analysis of blood pressure (BP) was used to study for the effects of ketanserin (Ket) on BP and blood pressure variability (BPV). Rats were instrumented chronically and BP was sampled every 4 ms by a computer from 2:00 to 14:00. Then a single dose of Ket (3 mg.kg-1) was given iv. BP and heart period (HP) were recorded for the next 30 min. The results showed that Ket lowered systolic BP (26.7 kPa to 21.1 kPa), diastolic BP (20.5 kPa to 15.8 kPa), and systolic BPV (1.3 kPa to 0.94 kPa). Otherwise, a positive relationship was found between antihypertensive effects of Ket and BPV. These findings may be of importance in antihypertensive treatment.
To determine the vascular selectivity, the inhibitory effects of verapamil (Ver), neferine (Nef), and tetrandrine (Tet) on the spontaneous contractile force of portal vein and contractile force of the paced papillary muscle of left ventricle were studied in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The vascular selectivity was expressed by the IC50 ratio (IC50 for papillary muscle/IC50 for portal vein). The results showed that the vascular selectivity values of Ver, Nef, and Tet were 1.15, 0.32, and 0.20, respectively in WKY and 0.80, 0.24, and 0.10, respectively in SHR. It is concluded that Nef and Tet, in contrast with Ver which is devoid of selectivity for either tissue, are more liable to inhibit the myocardium than the vascular smooth muscle. In addition, the IC50 value of Tet for inhibition of the portal vein in SHR was nearly 10-fold higher than that in WKY (237 and 27 mumol.L-1, respectively). This indicates that the response of portal vein to Tet is decreased in SHR.
Effects of serotonin (5-HT) and norepinephrine (NE) on neuronal activities of the nucleus tractus solitarii (NTS) were investigated in rat medullary slice preparations. The spontaneous discharges after perfusion of slices with 5-HT (1 mumol.L-1, 3 min) were increased in 25 (58.1%), reduced in 13 (30.2%), and unchanged in 5 (11.7%) neurons. Afer perfusion of slices with NE (1 mumol.L-1, 3 min), the spontaneous discharges were reduced or ceased in 27 (62.8%), increased in 13 (30.2%), and unchanged in 3 (7.0%) neurons. Responding to both 5-HT and NE were 38 (88.4%) neurons, among which 21 were selected for studying the effect of ketanserin (a new 5-HT2 blocker). The spontaneous discharges were more increased in 10 (47.6%) and reduced in 4 (19.0%) neurons after perfusion of ketanserin+NE than after perfusion of NE alone. These results indicate that there is an interaction between 5-HT2 receptor and alpha 2 adrenoceptor at NTS level, suggesting that the central action of ketanserin may be one of its antihypertensive mechanisms.
The effects of silybin (Sil) on myocardial infarction size and ischemia- and reperfusion-induced arrhythmias were studied in anesthetized open chest Sprague-Dawley rats. It was found that pretreatment with Sil 20, 50, and 80 mg.kg-1 iv reduced significantly infarct size by 34.7%, 35.0%, and 50.6% respectively at 4 h after ligation. Sil prevented ischemic arrhythmia only at the dose of 80 mg.kg-1. In reperfusion experiment, pretreatment with Sil 20 mg.kg-1 decreased significantly reperfusion-induced arrhythmia.
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Tetrandrine (Tet) 5 mg.kg-1 i.v. inhibited the pressor action of norepinephrine (NE) release induced by electric stimulation (10 V, 0.5-16 Hz) of spinal cord T11-L2. However, Tet 5 mg.kg-1 ia did not obviously attenuate the hypertensive responses to NE 0.51-16.91 micrograms.kg-1 i.v., indicating that Tet did not affect the alpha 1-adrenoceptors-mediated vasoconstriction. Tet 5 mg.kg-1 ia decreased the pressor responses to NE 0.05 and 0.17 micrograms.kg-1 i.v. and markedly reduced the dose-dependent hypertensive responses to B-HT920 i.v., a selective alpha 2-adrenoceptor agonist, proving that Tet reduced alpha 2-adrenoceptors-mediated vasoconstriction.
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1. Cardiac baroreflex sensitivity (BRS) and its sympathetic and vagal components were studied after atropine and propranolol administrations in conscious genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) rats of the Lyon strain at 5, 9, 13 and 70 weeks of age. 2. LH rats older than 9 weeks exhibit a lower BRS than age-matched LN and LL controls. 3. The vagal component of cardiac baroreflex is predominant. In LN rats, this component increases up to 9 weeks of age. 4. The sympathetic component of cardiac baroreflex is small and identical in the three strains and does not alter with age. 5. Thus, in normotensive rats, the increase in BRS during maturation reflects mainly the vagal component. The development of hypertension prevents this physiological increase in the sensitivity of the vagal component of cardiac baroreflex leading to a reduced BRS.
The influence of blood pressure (BP) level and age on the baroreflex sensitivity (BRS) and its autonomic nervous components was studied in genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) rats of the Lyon strains at 5, 9, 13 and 70 weeks of age. BRS was computed as the slope of the closest relationship, according to the cardiac response delay, between systolic blood pressure (SBP) and heart period changes induced by phenylephrine injections (3 micrograms/kg, i.v.) BRS and the relative importance of vagal and sympathetic components were determined in 4 conditions: 1) basal; 2) after beta-adrenergic blockade (propranolol, 2 mg/kg i.v.); 3) after vagal blockade (atropine, 2 mg/kg i.v.); 4) after vagal and beta-adrenergic blockade (atropine and propranolol, 2 mg/kg, i.v. each). At 5 weeks of age, BRS did not differ between the 3 strains (0.50 +/- 0.05, 0.69 +/- 0.10 and 0.62 +/- 0.09 ms/mmHg in LH, LN and LL rats respectively). In LN rats, BRS increased sharply between 5 and 9 weeks (1.25 +/- 0.12 ms/mmHg) and then remained stable until 70 weeks of age (1.19 +/- 0.14 ms/mmHg). Such an increase did not occur in LH rats and their BRS value was lower than that of LN and LL controls starting from 9 weeks of age. The vagal component of BRS was found to be more important than the sympathetic one in adult rats whatever the strain (80 p. 100 vs 20 p. 100).(ABSTRACT TRUNCATED AT 250 WORDS)
To determine precisely the influence of high blood pressure and age on the baroreflex sensitivity (BRS), we measured it in conscious genetically hypertensive (LH), normotensive (LN) and low-blood pressure (LL) rats of the Lyon strains. Groups of male rats were studied at the age of 5, 9, 13, 21 and 40 weeks. Using our previously described technique, their blood pressure (BP) and heart period (HP) were recorded beat by beat, in the conscious unrestrained state. Each animal received 2 or 3 i.v. injections of phenylephrine (PHE, 5 micrograms/kg) and nitroglycerin (NG, 100 micrograms/kg). The BRS (msec/mmHg) was computed as the slope of the closest relationship found between systolic BP (SBP) and HP changes. Otherwise, in the 13-week-old rats, BRS had been measured in basal conditions, after vagal blockade (atropine: 2 mg/kg i.v.) and after beta-adrenergic blockade (propranolol: 2 mg/kg) so as to determine the relative importance of vagal and sympathetic components of the baroreflex. In LN and LL rats, the BRS measured with PHE and NG increased markedly between 5 and 9 weeks of age and then remained stable in LN rats or decreased between 21 and 40 weeks of age in LL rats. In LH rats, BRS remained stable between 5 and 9 weeks of age and increased slightly up to 21 weeks of age. Significant differences between LH and LN rats were observed starting from 9 weeks of age when BRS was measured with PHE and only at 9 weeks of age when it was measured with NG injections. In 13-week-old rats, the cardiac baroreflex response was estimated to depend for 82 p. 100 and 18 p. 100 upon vagal and sympathetic components respectively when BRS was measured with PHE injections and of 68 p. 100 and 32 p. 100 when it was measured with NG injections.(ABSTRACT TRUNCATED AT 250 WORDS)