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

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:Studies in genetically hypertensive rats and their normotensive Wistar-Kyoto control rats have revealed a linkage of a chromosomal region containing the angiotensin converting enzyme (ACE) gene with blood pressure. This led to the hypothesis that ACE is a possible candidate gene for primary hypertension in humans. We defined the genotypes and allele frequencies of an insertion—deletion (I/D) polymorphism in parental couples who both had either high or low blood pressure and in their offspringSubjects:Parents (n = 111) and offspring (n = 75) with defined blood pressure status from the Dutch Hypertension and Offspring StudyMethods:Genomic DNA was amplified by polymerase chain reaction using primers flanking the polymorphic region in intron 16 of the ACE gene. Alleles were detected on agarose gels stained with ethidium bromideResults:Allele frequencies for the D-allele were similar in parents with high (0.66) and low blood pressure (0.59) and in their offspring (0.67 and 0.69, respectively). A similar lack of difference was found with respect to the complementary l-alleleConclusion:In the present rather large sample we failed to find a significant association between I/D polymorphism of the ACE gene and blood pressure status in subjects with high or low blood pressure and in their offspring

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:11β-Hydroxysteroid dehydrogenase (11β-HSD), by converting the active steroids cortisol and corticosterone to their inactive metabolites, regulates steroid exposure to the mineralocorticoid and glucocorticoid receptors. We explored the hypothesis that a defect in 11β-HSD could result in overstimulation of either the mineralocorticoid or glucocorticoid receptors with subsequent hypertension in an established animal model of hypertension, the Bianchi–Milan hypertensive (BMH) ratDesign and methods:Groups of BMH rats with established hypertension (42–46 days old) and prehypertensive rats (22 days old) were compared with age-matched normotensive control rats. Kidney and liver 11β-HSD and glucocorticoid receptor messenger RNA (mRNA) levels were assessed by Northern and dot-blot analyses, and 11β-HSD activity as percentage conversion of [3H]-corticosterone to [3H]-11-dehydrocorticosterone by tissue homogenateResults:Hepatic 11β-HSD activity and gene expression were significantly reduced in the hypertensive BMH rat compared with its normotensive genetic control. 11β-HSD activity was also reduced in the prehypertensive BMH rat (aged 25 days) from hypertensive parents, excluding hypertensionper seas the cause of the abnormality. Plasma corticosterone was higher in the hypertensive rats. There was no difference in renal 11β-HSD activity or gene expression between hypertensive and normotensive BMH rats, or in glucocorticoid receptor gene expression in the liver or kidneyConclusions:Normal levels of renal 11β-HSD mRNA and activity are found in the BMH rat. However, the hypertensive BMH rat does demonstrate impaired hepatic 11β-HSD activity which occurs at a pretranslational level, although it is not clear how this relates to the pathogenesis of hypertension in this model

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To determine whether alterations in cardiac G-protein number or function, or both, are involved in the desensitization of adenylate cyclase responsiveness in the hypertensive stateDesign:Quantitation of G-protein subunits in myocardial membranes from four different rat models of hypertension in comparison with respective normotensive ratsMethods:We compared male and female adult spontaneously hypertensive rats (SHR) with age- and sex-matched Wistar-Kyoto (WKY) rats, rats from the highest-pressure quartile from an F2generation of WKY x SHR hybrids with those from the lowest-pressure quartile, and one-kidney, one clip renal hypertensive with shamoperated rats. The function of GSαwas quantitated by reconstitution of cardiac cholate extracts into cyc—cell membranes with subsequent measurement of NaF-stimulated adenylate cyclase activity. The amounts of immunodetectable CSα, Giα,Gqα, and Gβ were determined from quantitative Western blotting experiments with[125l]-protein A detectionResults:None of the parameters investigated differed significantly between hypertensive and normotensive rats in any of the models investigatedConclusion:We conclude that major quantitative alterations in cardiac Gs, Gjor Gqare not a general feature of the hypertensive state

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:Spontaneously hypertensive rat (SHR) myocardium is known to exhibit reduced β-adrenergic agonist-stimulated adenylyl cyclase activity. As G-proteins play a pivotal role in transducing information from the receptor to adenylyl cyclase, a study was undertaken to assess whether changes in G-protein expression and functioning could explain thisDesign:Studies were performed in plasma membrane homogenates from vascular tissue (myocardium) from 11-week-old SHR (weighing 255 g) and control rats from both Wistar-Kyoto (WKY) and Wistar strains. Similar studies were performed in non-vascular tissue (renal cortical plasma membranes) to assess whether any observed changes are part of a more widely distributed membrane defectMethods:G-protein function was inferred from studies of adenylyl cyclase activity and levels of G-protein subunits (Gsα, Giα1, Giα2, Giα3, Goαand β) were assessed by immunoblottingResults:Differences in adenylyl cyclase activity were seen in SHR compared with WKY rat myocardium: in WKY rats adenylyl cyclase activity was greater than in SHR under forskolin-stimulated conditions and in the presence of fluoride and several ligands which couple to the catalytic unit of adenylyl cyclase via Gs, including the receptor-linked species prostaglandin E1glucagon and isoproterenol. However, with the exception of forskolin-stimulated activity, which in SHR was greater than in Wistar rats, SHR myocardial adenylyl cyclase activities were similar to those in Wistar rat membranes. Immunoblotting studies showed similar levels of G-protein subunits in all three strains. Studies of renal cortical plasma membranes failed to identify any differences in adenylyl cyclase activity or in G-protein subunit levelsConclusions:SHR, WKY rats and Wistar rats exhibit differences in myocardial adenylyl cyclase activity which are not seen in renal cortical plasma membranes. These are not related to hypertension or to differences in G-protein levels, and probably reflect strain differences in Gsfunction

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objectives:To clarify the involvement of prostaglandins and renal haemodynamics in the pathogenesis of salt-induced hypertension.Design:Young (6-week-old) spontaneously hypertensive rats (SHR), a salt-sensitive hypertensive model, were used.Methods:The effect of long-term (4-week) administration of cicletanine (50mg/100g in the diet), which stimulates prostaglandins synthesis, was examined concerning the development of hypertension in young SHR fed on 8% salt-containing diet. Whether the cyclo-oxygenase inhibitor indomethacin (3.0 mg/kg per day for the last 4 days of the treatment) attenuates the hypertension was also studied. Renal haemodynamics were examined by clearance of inulin (glomerular filtration rate) and para-aminohippurate (renal plasma flow)Results:Salt loading significantly accelerated the development of hypertension, and the salt-induced blood pressure rise was significantly attenuated by cicletanine, although cicletanine did not attenuate the spontaneous development of hypertension. The hypotensive effect of cicletanine was abolished by indomethacin. Glomerular filtration rate and renal blood flow were not changed with these treatments. However, the changes in renal vascular resistance were parallel to those in mean blood pressure: it was increased with salt loading, reversed by cicletanine and increased by indomethacin. Salt loading decreased urinary prostaglandin E2, cicletanine reversed the effect of salt loading and indomethacin inhibited the effect of cicletanineConclusions:The present findings suggest that the abnormality in prostaglandin E2contributes to the increased salt sensitivity in young SHR, probably through renal haemodynamic changes

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To study the contribution made by central endothelin to cardiovascular regulation in spontaneously hypertensive rats (SHR) and Wistar–Kyoto (WKY) controls.Methods:Central endothelin binding was measured with receptor autoradiography. The baroreceptor heart rate reflex was measured by sigmoidal curve-fitting of the mean arterial pressure and heart rate responses evoked by alternating intravenous injections of nitroprusside or phenylephrine. The baroreflex gain was derived as a function of the heart rate range and the curvature coefficientResults:Autoradiographic experiments with [125I]-endothelin-1 showed low to moderate binding in various medullary nuclei involved in cardiovascular regulation, such as the nucleus tractus solitarius and the ventrolateral medulla. A moderate binding density was found in regions such as the hypoglossal nucleus and the spinal trigeminal nucleus, whereas a high binding density was observed in the molecular layer of the cerebellum. The binding density was significantly lower in the ventrolateral medulla of SHR than in that of WKY rats, but there were no differences in other medullary regions. Compared with WKY rats, the SHR had higher mean arterial pressures and heart rates but tended to have a reduced baroreceptor heart rate reflex gain. This latter change was entirely attributed to a significantly lower heart rate range, caused by an elevated lower heart rate plateau in SHR. The intracisternal injection of endothelin-1 at 25 pmol/kg did not influence the resting mean arterial pressure or heart rate, but it caused a significant increase in baroreflex gain, in both SHR and WKY rats. The extent of the effect was similar in the two strains and was attributed to a significant increase in the curvature coefficient of the sigmoidal baroreflex curve. Consequently, the range over which blood pressure changes evoked reflex changes in the heart rate was reduced by endothelin-1 treatment in both SHR and WKY rats. The heart rate range was not affected and remained different between SHR and WKY rats after the endothelin-1 injection. The intracisternal injection of endothelin-3 at 25 pmol/kg, but not at 2.5 pmol/kg, had effects similar to those of endothelin-1 on the baroreflexConclusions:These results show that binding sites for endothelin-1 are present in various regions of the hindbrain of SHR and WKY rats and that central administration of endothelin-1 sensitizes the baroreceptor heart rate reflex. However, this latter effect is similar in SHR and WKY rats and is mediated by a mechanism which is distinct from that underlying the difference in reflex sensitivity between these strains

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID