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:

Background:Segregation studies using genomic polymorphisms on F2progeny obtained from hypertensive rat models showed that a putative hypertensive gene is located close to the angiotensin converting enzyme (ACE) gene. However, it was suggested that additional major genes should contribute to the pathogenesis of hypertension.Methods:F2rats were obtained from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats of Izumo colony. Blood pressure was measured with a photoelectronic oscillometric tail-cuff method before and during salt loading. Genomic DNA was extracted from livers and digested with Haelll or Rsal. DNA fingerprinting was performed with 26 32P-labelled human variable number of tandem repeats markers.Results:Eighty-seven fingerprint bands polymorphic between SHRSP and WKY were obtained. When the distribution of these bands in the F2progeny was studied, one fingerprint band (1/MCT96.1) showed a distorted distribution between the high- and low-blood pressure subpopulations of the F2rats, suggesting that the band cosegregated with blood pressure. When blood pressure was compared between the F2rats with [( + ) rats] and without [( - ) rats] the 1/MCT96.1 band, it was found that (-) rats had significantly higher basal and salt-loaded blood pressures than ( + ) rats. The 1/MCT96.1 locus was also shown to have no positive linkage with the ACE locus.Conclusion:The present study showed that examination of the allele distribution between subpopulations with extreme phenotype can be used in the screening of loci cosegregating with blood pressure. Furthermore, a locus not in the ACE region, showing cosegregation with blood pressure in F2progeny from SHRSP and WKY rats, was found.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objectives:The SA-gene shows markedly higher levels of expression in the kidneys of spontaneously hypertensive rats (SHR) than in their non-hypertensive reference strain, the Wistar-Kyoto (WKY) rat. Based on the important role of the kidney in blood pressure regulation, the possibility has been raised that this gene, the translational product of which remains unknown, may participate in the pathogenesis of primary hypertension. The present study was conducted to test this hypothesis and to ascertain the chromosomal localization of the SA-gene.Design:A cosegregation study was performed using an F2intercross between strokeprone SHR (SHRSP) and WKY rats, and a previously described restriction fragment length polymorphism of the SA-gene for characterization of genotype. Mapping of the SA-gene was accomplished by screening a somatic cell-hybrid panel and by linkage group analysis.Results:A statistically significant difference in systolic blood pressure was found after sodium loading, but not under basal conditions between groups of rats defined by zygosity at the SAlocus, consistent with a hypertensive effect of the SHRSP allele. No effect of SAgenotype on diastolic blood pressure was observed. The SA-gene was localized on rat chromosome 1.Conclusions:This study establishes the SAlocus on chromosome 1 as a region in which a gene or genes contributing to blood pressure regulation in this model are localized, and provides further evidence for a possible role of the SA-gene in the pathogenesis of hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To determine whether elevated microviscosity is associated with elevated arterial pressure in segregating (F2) hybrids produced by crossing stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats.Methods:SHRSP and WKY rats were obtained from the colony at the University of Heidelberg. F2progeny were obtained by brother—sister mating of the F1progeny of the cross between SHRSP and WKY rats. Membrane microviscosity (the inverse of fluidity) was measured as a fluorescence anisotropy of trimethylammonium diphenylhexatriene incubated with the erthrocyte membranes. The measurements were made using a luminescence spectrometer with computer-controlled excitation and emission polarizers.Results:Membrane microviscosity was significantly greater (fluidity was lower) in erythrocyte membranes obtained from SHRSP than in those obtained from WKY rats. In the F2cohort there were no significant correlations between membrane microviscosity and systolic blood pressure, diastolic blood pressure, salt-loaded systolic blood pressure or salt-loaded diastolic blood pressure. A similar lack of relationship between these parameters was shown in a subgroup analysis, in which males or females with a male WKY rat progenitor and males or females with a male SHRSP progenitor were analysed separately.Conclusions:Erythrocyte membrane microviscosity is elevated in SHRSP compared with WKY rats. In segregating F2hybrid rats the membrane microviscosity trait does not correlate with blood pressure. These results eliminate the microviscosity trait as being directly related to the cause of genetic differences in blood pressure between WKY rats and SHRSP.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To study the effects of renin-angiotensin system blockade by a novel non-peptide angiotensin II receptor antagonist, losartan, on development of hypertension and acceleration of end-organ damage in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP).Design and methods:One hundred and eighty-one male SHRSP were fed a 4% sodium diet from 6 to 18 weeks of age. Seventy-eight SHRSP were treated orally with losartan, 30 mg/kg per day. One hundred and three rats constituted untreated controls. Blood pressure, plasma renin activity (PRA), renal function and end-organ damage were monitored during the transition to malignant hypertension.Results:Losartan prevented a blood pressure rise during the first 4 weeks of salt loading. Thereafter, blood pressure rose slowly in losartan-treated rats; however, at each time-point studied blood pressure was significantly lower in losartan-treated rats than in control rats. Losartan treatment increased PRA during the first 4 weeks, but this effect was not sustained. Thereafter, PRA decreased to control (week 0) levels. In contrast, 2 weeks after high-sodium feeding started, untreated SHRSP failed to suppress PRA appropriately; thereafter, PRA rose significantly. Losartan affected renal pathophysiology by blunting the decline in glomerular filtration rate, controlling proteinuria and preventing or delaying the appearance of malignant nephrosclerosis. Losartan treatment significantly increased survival and completely prevented cerebrovascular infarcts.Conclusions:The results indicate that angiotensin II blockade markedly reduces both hypertension and end-organ damage in chronically salt-loaded SHRSP and that the renin—angiotensin system may play an important role in the development of hypertensive cardiovascular disease in SHRSP.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objectives:Recent studies have found vasopressin to be antinatriuretic as well as antidiuretic. We therefore wished to determine the endogenous renal activity of vasopressin in spontaneously hypertensive rats (SHR) and one-kidney, one clip hypertensive (1K1C) rats.Methods:The renal effects of a vasopressin (V2) antagonist, [d(CH2)5,D-lle2,lle4]-arginine vasopressin (0, 10 or 30nmol/kg), were compared in SHR and 1K1C rats and their respective controls, the Wistar-Kyoto (WKY) rat and the Sprague-Dawley rat.Results:The V2antagonist produced a dose-related increase in urine flow rate and free water clearance in all groups studied (WKY rats, SHR, Sprague—Dawley rats and 1K1C rats). Sodium excretion and osmolar clearance were increased only in the WKY rats and 1K1C rats. The response in the SHR was significantly less than that observed in the WKY rats. At both doses of V2antagonist investigated, the urine flow rate was two- to threefold greater in the WKY rats than in SHR, in spite of similar control levels. Conversely, the response oobserved in the acquired model of hypertension (1K1C rats) at the one dose of V2 antagonist investigated (30nmol/kg) was similar to that found in the control Sprague-Dawley rats, suggesting that the decreased response observed in SHR was not secondary to the increased blood pressure.Conclusions:These data demonstrate that the endogenous level of renal activity of vasopressin in SHR is suppressed compared with control WKY rats.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To clarify the role of calcium-binding proteins (CaBP) in hypertension.Design:CaBP from several organs of spontaneously hypertensive rats (SHR) and age-matched Wistar—Kyoto (WKY) rats were purified and their characteristics compared between the two strains. The CaBP were purified by applying the soluble cytosolic fractions from mesenteric vessels, heart, kidney and brain of 4- and 10-week-old SHR and WKY rats to a phenyl-Sepharose column. Felodipine binding to the purified CaBP was then measured.Results:The fluorescence intensity of felodipine increased in a calcium-dependent manner when it bound to CaBP. The pK0.5 Ca2+ values derived from the calcium ion—felodipine fluorescence curves for each CaBP preparation from organs of the two strains were similar, indicating that the calcium sensitivities of the CaBP to the felodipine binding process are similar in SHR and WKY rats. In 10-week-old SHR the mean levels of felodipine-bound CaBP in heart, brain and kidney were significantly altered compared with those in WKY rats. No such alterations were observed in heart, kidney and brain from 4-week-old SHR and WKY rats. Conversely, the mean levels of felodipine-bound CaBP in mesenteric vessels from 4- and 10-week-old SHR were reduced significantly compared with those of age-matched WKY rats.Conclusions:These results suggest that the levels of cytosolic felodipine-bound CaBP from heart, kidney and brain are altered in response to elevated blood pressure, and that reduced levels of felodipine-bound CaBP in the mesenteric vessels of SHR might be a primary characteristic of this rat strain.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objectives:Calcium blockade has been reported to inhibit the contraction of the vascular smooth muscle and the liberation of vasoactive substances by endothelial cells. We tested the effects of calcium blockade on the mechanical properties of the carotid artery in normotensive Wistar—Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) in the presence and in the absence of endothelium.Methods:The pressure-volume relationships of isolated carotid arteries were recorded in situ in SHR (n=20) and WKY rats (n=20) before and after calcium blockade by local incubation with clentiazem.Results:With intact endothelium, calcium blockade induced a significant shift in the pressure—volume curve in both strains, volume being significantly higher after calcium blockade than under control conditions. In WKY rats the carotid mechanical properties were similar after calcium blockade and after abolition of the smooth muscle tone by potassium cyanide (KCN) poisoning. In SHR the carotid compliance measured after incubation with clentiazem was significantly lower than that measured after KCN poisoning. Removal of the endothelium induced a significant shift in the pressure-volume curve towards the volume axis in both strains, and an increase in carotid compliance. Local incubation with clentiazem or KCN did not induce further modifications of the pressure-volume relationship either in WKY rats or in SHR. Furthermore, in SHR and WKY rat carotid arteries, the pressure-volume relationship and the compliance measured after incubation with clentiazem were identical in the presence and in the absence of endothelium.Conclusions:In WKY rat and SHR carotid arteries, acute calcium blockade increases the arterial compliance independently of the endothelium integrity. Furthermore, part of the compliance enhancement induced by the calcium antagonist could be related to an antagonizing mechanism of the production of endothelial constricting factor or factors.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To examine whether elevated intravascular pressure in chronic hypertension alters responses of vascular smooth muscle to agents of endothelial origin.Methods:Coarctation hypertensive, sham normotensive control, and one-kidney, one clip hypertensive (1K1C) rats were used. Tail systolic, carotid and femoral arterial pressures were measured. Responses to histamine, endothelin-1 and the prostacyclin analog iloprost were evaluated in isolated helically cut strips of thoracic and abdominal aortas, with and without endothelium, from all groups. Responses to nitroglycerin were also evaluated in strips of abdominal aortas.Results:Thoracic aortas from 1K1C and coarctation hypertensive rats, as well as abdominal aortas from 1K1C rats, but not abdominal aortas from coarctation hypertensive rats were exposed chronically to elevated arterial pressure. Endotheliumdependent maximal relaxation by histamine was significantly depressed in thoracic aortas from both groups of rats, as well as in abdominal aortas from 1K1C rats. Maximal relaxation and sensitivity to histamine were normal in abdominal aortas from coarctation hypertensive rats. Sensitivity to nitroglycerin was impaired in abdominal aortas from 1K1C rats but not in those from coarctation hypertensive rats; maximal relaxation to nitroglycerin was similar in all groups. Relaxation to iloprost was independent of the endothelium, observed only in thoracic aortas and impaired in hypertensive rats. Responses to endothelin-1 were similar in the groupsConclusion:Vasorelaxation by histamine, iloprost and nitroglycerin are impaired in hypertension. The impaired relaxation by histamine results from exposure of the vascular endothelium to chronically elevated pressure. This impairment may be related to effects of high pressure in reducing the ability of the endothelium to produce endothelium-derived relaxing factor and inhibit cyclic CMP-dilator mechanisms.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID