ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:The genetic divergence of inbred Dahl salt-sensitive (SS/Jr) rats from inbred Dahl salt-resistant (SR/Jr) rats and various other inbred strains was measured.Design:Structural differences in DNA between strains were evaluated.Methods:Genetic variants were sought (1) by restriction fragment length polymorphism (RFLP) analysis, using 19 DNA probes, (2) by the polymerase chain reaction around microsatellites and (3) by DNA sequencing.Results:It was estimated that 1 in 1532 bases of DNA were different between the SS/Jr and SR/Jr strains. In comparing SS/Jr and SR/Jr rats, it was also observed that one DNA probe in 10 will yield multiple RFLP, presumably as the result of large insertion/deletion events. A comparison of SS/Jr rats with seven other inbred strains showed that the percentage of loci that carry alleles different from SS/Jr rats varies from about 23% for Albino Surgery rats to 71% for Brown Norway rats. Conclusions: Although the SR/Jr strain is an appropriate contrasting strain for the genetic analysis of hypertension in SS/Jr rats, a genetic analysis involving crosses of SS/Jr rats and unrelated inbred strains is also likely to be useful in identifying genes that cosegregate with blood pressure because more informative genetic markers will be available than in a cross of SS/Jr with SR/Jr rats

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:The present investigation was undertaken to determine whether p34cdc2, a cell-cycle regulatory kinase, is involved in the manifestation of the altered proliferation evident in fibroblasts isolated from spontaneously hypertensive rats (SHR).Design:Experiments were performed on quiescent aortic adventitial fibroblasts stimulated to re-enter the cell cycle in order to examine the timing of cell cycle-related events.Methods:The cell-cycle phase was determined by flow cytometry and was related to the cellular content and kinase activity of p34cdc2.Results:SHR fibroblasts displayed a heightened basal level of p34cdc2at quiescence relative to Wistar-Kyoto (WKY) rat cells. Both SHR and WKY fibroblasts showed a cell cycle-dependent increase in p34cdc2content, beginning in S phase. However, the SHR adventitial fibroblasts exited Go—G-] several hours earlier than the WKY fibroblasts as indicated by the time of initiation of DNA synthesis and increase in activity of p34cdc2. Conclusions: SHR aortic adventitial fibroblasts appear to have a heightened proliferative capacity relative to WKY fibroblasts, which is evident in a quicker exit from Co and faster transition to DNA synthesis, followed by the earlier activation of p34cdc2

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:The aim of the study was to evaluate the influence of renal sympathetic nerves on the production of interleukin (IU-6 in the kidney of normotensive Wistar rats and spontaneously hypertensive rats (SHR).Design:In acute studies, the left kidney was exposed and the renal nerves were electrically stimulated to decrease renal blood flow by either 15 or 30% for 1 h. The changes in renal function induced by nerve stimulation were measured and IL-6 production estimated at the end of the experiment.Method:Pentobarbitone anaesthetized rats were prepared for the measurement of renal blood flow, glomerular filtration rate and water and sodium excretion. IL-6 production was estimated by the level of IL-6 messenger (m)RNA present in the kidney tissue.Results:At the lower level of nerve stimulation there were reductions in the glomerular filtration rate of 12 and 24% in Wistar and SHR, respectively, and a decrease in sodium excretion of approximately 30% in both rat strains. At higher rates of stimulation these haemodynamic and tubular responses were proportionately larger. The mRNA for IL-6 and P-actin were measured by densitometric analysis of Northern blot gels following hybridization. Renal IL-6 mRNA levels in the Wistar rat demonstrated that the gene was actively expressed and was increased some threefold by renal nerve stimulation. By contrast, IL-6 mRNA was extremely low in SHR compared with that found in the kidneys of Wistar rats and did not appear to be changed by renal nerve stimulation.Conclusions:These findings suggest that the renal sympathetic nerves are an important regulatory mechanism for IL-6 production under normal conditions. However, in the SHR, production of IL-6 in the kidney appears to be suppressed.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To characterize [125l]-atrial natriuretic factor [ANF-(99-126)l binding sites in the renal preglomerular microvasculature of Sprague-Dawley rats.Methods:Renal preglomerular microvessels were isolated by infusion of a magnetized iron oxide solution into the renal arteries and detachment from non-vascular tissue by a magnetic field. In order to characterize [125l]-ANF-(99-126) binding sites, saturation and competitive binding experiments were performed. To evaluate the proportions of ANF receptor subtypes (ANF-R1, ANF-R2), competition curves were charted in the presence of 10-6mol/l C-ANF-(4-23), a specific ligand of ANF-R2 (ANP-C).Results:[25I]-ANF binding to vascular membranes was saturable and of high affinity. Equilibrium saturation binding curves suggested the presence of one group of high-affinity receptors [equilibrium dissociation constant (Kd) 22±6pmol/l; binding capacity (Bmax) 118±6fmol/mg protein]. In competitive inhibition experiments, no significant differences were found in binding capacity between experiments performed either in the presence or in the absence of an excess (1 u,mol/l) of C-ANF (94 ± 27 versus 151±35fmol/mg protein, respectively), suggesting that most receptors in the renal vasculature are of the subtype ANF-R1. Incubation of renal microvessels with ANF-(99-126) stimulated cyclic GMP production in a dose-related manner. In parallel studies, the proportion of ANF-R1 (ANP-A, -B) and ANF-R2 (ANP-C) receptors in glomeruli, calculated from competitive inhibition experiments, was 86 ± 2 and 14 ±2%, respectively (P<0.005).Conclusions:These results indicate that rat renal preglomerular microvessels contain a high proportion of guanylate cyclase-coupled ANF-R1 (ANP-A, -B) and a low density of ANF-R2 (ANP-C) receptors. This difference in the proportion of ANF receptor subtypes, compared to that reported in glomeruli and other vascular beds, may have physiological significance.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objectives:Abnormalities in platelet calcium handling have been reported in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats. Furthermore, several reports have indicated that WKY rats differ from both SHR and Wistar rats. The objectives of the present study were to investigate platelet calcium handling in three normotensive stains and in SHR, and to confirm the abnormal calcium mobilization in SHR.Design and methods:We compared calcium handling in fura-2-loaded platelets of SHR, Wistar, Sprague-Dawley (SD) and WKY rats.Results:The basal cytosolic free Ca2+concentration in platelets was significantly higher in SHR and significantly lower in SD rats than in the other strains. The intracellular Ca2 +response to thrombin in the presence of extracellular Ca2+was greater in SHR than in the three normotensive strains. The thrombin-induced intracellular Ca2+rise in the absence of extracellular Ca2+was also greater in SHR and lower in SD rats than in the other strains. However, there was no significant difference among SHR, WKY and Wistar rats at higher doses of thrombin. The intracelluiar ionomycin-released calcium fraction, which may indicate the size of intracellular calcium stores, was similar in SHR, WKY and Wistar rats, and was greater than in SD rats. No difference was detected between WKY and Wistar rats in resting and peak agonist-evoked intracellular Ca2 +concentrations.Conclusions:These results show that calcium handling in WKY rats is similar to that in Wistar rats with respect to platelet calcium metabolism and confirm the abnormality in SHR. Furthermore, the enhanced intracellular Ca2+response to thrombin in SHR was not dependent on the size of ionomycin-released Ca2+stores. In addition, substantial differences in platelet calcium handling may occur even among normotensive strains if the strains are not related.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:The present study was designed to investigate the influence of hypertension and of long-term treatment with the dihydropyridine calcium antagonist isradipine on the morphology of the femoral artery in spontaneously hypertensive rats (SHR).Design:Systolic blood pressure (SBP), body weight and morphology of the femoral artery were evaluated, and the ultrastructure of the endothelium was analysed by transmission and scanning electron microscopy.Methods:SHR were divided into three groups, a control group which was left untreated and two isradipine treatment groups, one at 0.01 mg/kg per day and the other at 0.1 mg/kg per day. Two age-matched groups of Wistar–Kyoto (WKY) rats were included in the study; one group was left untreated and was used as a normotensive reference group and the other was treated with isradipine at 0.1 mg/kg per day. The study lasted 12 weeks.Results:SBP did not change in the WKY rats, whether treated with isradipine or not, but was significantly increased in SHR as a function of age. The lower dose of isradipine did not alter SBP in the SHR, but the higher dose brought SBP values into the normal range after the first week of treatment.Light microscopy of sections of the femoral artery did not reveal any structural differences in the five rat groups examined. Both transmission and scanning electron microscopy showed endothelial alterations in the SHR, together with thickening of the internal elastic lamina. Treatment with isradipine significantly improved the morphology of the endothelium in SHR. The higher dose was more effective, but the lower dose partly countered the hypertension-dependent changes in the morphology of the endothelium. No significant modifications to the structure of the endothelium were noticed in isradipine-treated WKY rats compared with untreated WKY rats.Conclusions:The results show that structural changes occur in the endothelium of the femoral artery of SHR and that isradipine treatment has a protective effect. This protective effect is probably only partly dependent on the antihypertensive properties of the compound.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To determine whether the reduced baroreceptor-heart rate reflex sensitivity in genetically hypertensive rats is related to the level of cardiac or vascular hypertrophy.Design:Young spontaneously hypertensive rats (SHR), stroke-prone hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats were treated chronically with the angiotensin converting enzyme (ACE) inhibitor perindopril in different regimens in order to produce a wide-ranging combination of cardiac and vascular hypertrophy.Methods:All strains were treated with perindopril (0.1, 0.3, 1 or 3 mg/kg per day) in their drinking water from 4 until 9 weeks of age. Additional groups of SHR were treated with perindopril (3 mg/kg per day) from 4 until 12 weeks and from 4 until 14 weeks of age. At 13 weeks of age all animals were chronically instrumented with arterial and venous catheters. One week later, steady-state sigmoidal mean arterial pressure-heart rate reflex curves were obtained in the conscious rats by the injection of pressor and depressor agents before and after the administration of atenolol (1 mg/kg, intravenously) to determine the vagal component. The minimum and the maximum blood pressure produced by nitroprusside and methoxamine, respectively, after simultaneous ganglion and p-adrenoceptor blockade were used as an index of whole body vascular hypertrophy. The left ventricular to body weight ratio was measured at the end of the experiment.Results:At 14 weeks of age, mean arterial pressure, the maximum and minimum autonomically blocked blood pressure and the left ventricular to body weight ratio were 34, 20, 9 and 17% higher, respectively, in SHR, and 56, 35, 27 and 39% higher, respectively, in SHRSP than in WKY rats. Perindopril treatment dose-dependently reduced both cardiac and vascular hypertrophy but to different extents. The highest doses reduced mean arterial pressure and the autonomically blocked maximum and minimum blood pressure in both hypertensive strains to the levels of untreated WKY rats but approximately 50% of the cardiac hypertrophy was still present. The left ventricular to body weight ratio was normalized in SHR only with the longer term perindopril treatments. A comparison of the baroreflex function curves in untreated SHR and SHRSP showed that the vagal component of the heart rate range was markedly reduced compared to that in WKY rats. Treated SHRSP had a normal mean arterial pressure and a normal autonomically blocked maximum and minimum blood pressure, but their vagal heart rate range was only 63% of that in WKY rats. The heart rate range in SHR treated from 4 to 9 weeks of age was only marginally greater than that of untreated SHR, despite prevention of hypertension and vascular hypertrophy. In SHR treated from 4 until 12 weeks of age, which prevented cardiac hypertrophy, the vagal heart rate range was markedly greater. With perindopril from the age of 4 to 14 weeks, the vagal baroreflex heart rate range was similar to that of WKY rats. Thus the improvement in the vagal heart rate range was more closely related to the prevention of cardiac hypertrophy (r=0.73, P< 0.001) than vascular hypertrophy or a blood pressure elevation. Since there were no further changes in the indices of hypertrophy, the presence of the ACE inhibitor was likely to have been responsible for restoring the remaining 35% of the vagal baroreflex not affected by structural factors.Conclusions:These results suggest that prevention of cardiac rather than vascular hypertrophy is the major requirement for normalizing the vagal component of the baroreceptor-heart rate reflex in hypertensive rats. However, structural changes accounted for only about two-thirds of the vagal deficit. The remainder was restored by the presence of an ACE inhibitor, suggesting that the vagal component of the baroreceptor—heart rate reflex is normally suppressed by the renin-angiotensin system

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Aim:To study the spontaneous variability in regional haemodynamics.Methods:Twenty normotensive Wistar-Kyoto rats were chronically instrumented with an arterial catheter and with pulsed Doppler flowmeters on the distal aorta, and the superior mesenteric and left renal arteries. After surgical recovery, the rats were monitored in unrestrained conditions. The recorded signals were analysed beat-to-beat to obtain means and coefficients of variation for mean arterial pressure, heart rate, regional blood flow velocity (consecutive 0.8-s periods) and indices of regional vascular resistance (0.8-s ratio of mean arterial pressure to mean blood flow velocity).Results:Muscle and splanchnic blood flow velocities were markedly variable, with coefficients of variation of 12.8 ±0.8 and 12.2 ±1.7% (means ±SEM), respectively, about twice as large as the coefficient of variation for mean arterial pressure (6.2 ±0.3%). The renal blood flow velocity was slightly less variable than the muscle and splanchnic blood flow velocities, with a coefficient of variation of 10.4 ±0.8%, but still markedly and significantly more variable than systemic arterial pressure. A contingency analysis of paired variations in any two given parameters (arterial blood pressure, heart rate, blood flow velocities and indices of vascular resistance) showed a concordant pattern, the only exception being a distinctly discordant trend for the covariations in muscle and splanchnic blood flow velocities. Conclusions: Regional blood flow velocity and vascular resistance have a larger degree of spontaneous variability than systemic arterial pressure. Renal blood flow velocity is also highly variable, suggesting that short-term stimuli that affect the renal blood vessels are not countered by autoregulation to any great degree. We conclude that while central factors may drive concordant regional haemodynamic variations, some opposing changes in regional blood flow velocity may cancel each other out, thereby reducing the variability in systemic blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID