摘要:

This year marks the 60th anniversary of the publication of Goldblatt's original demonstration that constricting the renal arteries of the dog was capable of causing sustained elevation of arterial pressure [1]. The success of those experiments depended not only on the ingenious design of the adjustable silver clamps which narrowed the arteries, but also on the ability to make accurate recordings of systolic blood pressure from day to day via external carotid loops. Translation from the laboratory to clinical practice was slow, and 20 years elapsed before Howardet al.[2] were able to show amelioration of hypertension after nephrectomy in a series of six patients in whom renovascular disease was suspected. That early series did not use angiography, which only later became established as the main technique for diagnosis.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo determine the effects of hydronephrosis on glomerular number and juxtaglomerular cell synthetic activity and the protective influence of angiotensin converting enzyme inhibition.DesignA comparison of sham and contralateral kidneys with 8-week ipsilateral ureteral ligated hydronephrotic kidneys in BALB/c mice. Enalapril was administered from 5 weeks in additional sham and hydronephrotic kidney groups.MethodsRenin and prorenin immunohistochemistry was applied to sections of perfusion-fixed kidneys at the light and electron microscope level. Glomerular number was estimated by a physical disector-fractionator stereological method. An enzyme kinetic renin assay was performed in kidney tissue and plasma.ResultsGlomerular number in hydronephrotic kidneys decreased significantly compared with sham and contralateral kidneys. Renin content in hydronephrotic kidneys did not change compared with sham or contralateral kidneys, but the renin content in the glomerulus was significantly greater in hydronephrotic than in contralateral kidneys and similar to in sham kidneys. Contralateral kidneys enlarged significantly and their total renin content decreased significantly compared with hydronephrotic and sham kidneys. Plasma renin was unchanged. Fewer juxtaglomerular cells were labelled for renin and prorenin in contralateral than in hydronephrotic or sham kidneys. Granulopoiesis and exocytotic profiles were markedly greater in hydronephrotic than in contralateral or sham kidneys. Following enalapril, glomerular number was significantly higher in hydronephrotic kidneys and renin content increased proportionally more in contralateral than in hydronephrotic or sham kidneys.ConclusionHydronephrosis for 8 weeks results in atrophy of 50% of glomeruli and exerts an inhibitory influence on contralateral juxtaglomerular cells while augmenting ipsilateral renin production per remaining glomerulus with maintenance of plasma renin. Enalapril preserves glomeruli and reverses the contralateral inhibitory influence, suggesting an angiotensin-related mechanism.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveAlthough a decreased responsiveness to acetylcholine, an endothelium-dependent vasodilator, has been reported in arteries isolated from spontaneously hypertensive rats (SHR), the precise role of nitric oxide (NO) in thein vivoregulation of blood pressure is not clear. We investigated the effects of acetylcholine and of NG-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, on mean arterial pressure and the production of NO metabolites (nitrate and nitrite) in SHR and in Wistar-Kyoto (WKY) rats, their normotensive control strain.DesignWe determined serum levels of nitrate and nitrite before and after the intravenous injection of 40 μg/kg acetylcholine following the administration of L-NAME (30mg/kg) or its vehicle in adult SHR and WKY rats.ResultsAcetylcholine administration significantly reduced mean arterial pressure in both SHR and WKY rats, accompanied by a significant rise in serum nitrate and nitrite. Administration of L-NAME significantly increased the mean arterial pressure in SHR and in WKY rats. L-NAME inhibited the hypotension induced by acetylcholine and the rise in serum nitrate and nitrite both in SHR and in WKY rats.ConclusionThe release of NO stimulated by acetylcholine was unaltered in SHR, supporting previousin vitroresults.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo compare the protective effect against cardiac and renal damage of a β-blocker, an angiotensin converting enzyme inhibitor and a calcium antagonist in severely hypertensive rats.MethodsSix-week-old male spontaneously hypertensive rats (n = 24) were given 100 mg/kg deoxycorticosterone and a 4% NaCl diet. They were then treated orally with vehicle, atenolol (70 mg/kg), enalapril (5 mg/kg) or nisoldipine (7 mg/kg) for 8 weeks.ResultsControl (vehicle-treated) rats developed marked hypertension after 8 weeks. The antihypertensive effect of the three drugs was similar, as were the reductions achieved in cardiac weight and aortic thickness. However, histological examination revealed that nisoldipine was significantly more effective than the other drugs in reducing renal arteriolar lesions and renal glomerular sclerosis. Only nisoldipine significantly improved plasma creatinine and the glomerular filtration rate.ConclusionThese findings suggest that calcium antagonists have a renoprotective effect in severely hypertensive rats, which may derive from the inhibition of arteriolar damage and glomerular sclerosis.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveMagnetic resonance imaging (MRI) was used to investigate the therapeutic effects of imidapril, a newly synthesized angiotensin converting enzyme (ACE) inhibitor, on cerebral stroke lesions.DesignPretreatment with ACE inhibitors is known to prevent stroke in stroke-prone spontaneously hypertensive rats, prolonging their lifespan. Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) were treated with imidapril after the onset of stroke.MethodsM-SHRSP with proved stroke were divided into two groups. One group received 40mg/kg per day imidapril and the other group was used as a control. For 4 weeks, neurological symptoms were scored daily, and MRI images were taken and scored once a week.ResultsIn the control group the MRI score for cerebral lesions increased during the experiment, and seven out of eight control rats died within 17 days. In rats treated with imidapril the major finding was that imidapril rapidly ameliorated the damage to the blood-brain barrier and resolved brain oedema within 1 week. At the same time the neurological symptoms observed after stroke disappeared. Furthermore, none of the rats treated with imidapril showed recurrence of stroke, and their survival rate was improved.ConclusionThese results suggest that imidapril has therapeutic effects on stroke lesions, as well as prophylactic effects on the recurrence of stroke.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo investigate the relationship between testosterone and blood pressure during the rapid development phase of blood pressure rise in four strains of rats: Wistar–Kyoto (WKY) rats; spontaneously hypertensive rats (SHR); SHR/y, a substrain with an SHR Y chromosome and WKY rat autosomes and X chromosomes; and SHR/a, a substrain with SHR autosomes and X chromosomes and the WKY rat Y chromosome.MethodsBlood pressure was measured every 2 weeks by the tail-cuff method, and was verified in selected rats at 23 weeks by aortic telemetry. Serum testosterone was measured, by radioimmunoassay, every 2 weeks from 5 to 23 weeks of age.ResultsDuring the rapid phase of blood pressure rise, between 5 and 9 weeks of age, there was a significantly larger rise in serum testosterone in SHR and SHR/y than in WKY rats and SHR/a groups. The hypertensive Y chromosome in the SHR and SHR/y accelerated peak testosterone approximately 4 weeks earlier, and blood pressure was increased in these two groups compared with the SHR/a and WKY rat groups, respectively. A gene on the SHR Y chromosome (Tty) affecting the timing of testosterone in development is proposed. At approximately 15 weeks of age testosterone levels decreased sharply towards prepubertal levels in WKY rats and at 23 weeks in SHR/y, whereas testosterone levels were maintained in SHR and SHR/a, which suggests an autosomal component.ConclusionThe SHR Y chromosome may accelerate the start of puberty and a cascade of molecular and neuroendocrine events that raise blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo examine the mechanism of increased Na–H antiport activity in tissues of the spontaneously hypertensive rat (SHR) by measuring the amount of sodium–hydrogen exchanger isoform 1 (NHE-1) in cultured vascular and striated muscle cells, and in exvivotissue extracts of membranes from the brain, heart, kidney and skeletal muscle.MethodsA polyclonal rabbit antibody was raised against a fusion protein consisting of a section of the carboxyl tail of NHE-1 and β-galactosidase. Cell extracts were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and proteins were transferred to supported nitrocellulose. NHE-1 was detected by Western blotting and quantified by densitometry.ResultsCultured aortic and striated muscle cells from SHR contained similar amounts of NHE-1 on Western blots to those from control Wistar-Kyoto (WKY) rat cells.Ex vivoextracts of crude membranes from SHR tissues also contained quantities of NHE-1 similar to those from WKY rat tissues.ConclusionThe increased Na–H antiport activity observed in SHR cellsin vitroandin vivois not due to an increased amount of NHE-1 protein in SHR cells. This suggests that in this model of hypertension the increased transport activity results from an increased turnover number per NHE-1 molecule.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

DesignThe membrane current mediated by the L-type calcium channel (ICa) was studied for myocytes isolated from the ventricle of 10− to 11-week-old spontaneously hypertensive rats (SHR).ResultsCompared with age-matched normotensive Wistar-Kyoto (WKY) or Sprague-Dawley rats, the amplitude of ICawas greater for the SHR. Two observations suggest that the greater ICaof the SHR was not due to hypertrophy. First, the similarity of membrane capacitance for these three strains of rat indicated lack of hypertrophy. Secondly, the amplitude of ICawas also greater for myocytes isolated from the right ventricle of the SHR. The ICaof the SHR was more sensitive to drugs known to activate calcium channels via phosphorylation. Specifically, extracellular application of 1 μmol/l isoprenaline as well as intracellular dialysis with either 1 mmol/l cyclic AMP or with 1 mmol/l adenosine 5′-O-3-thiotriphosphate increased the mean ICaof SHR myocytes significantly more than that of WKY rat cells. The ICaof SHR myocytes was also more sensitive to BAY K 8644 and its enantiomorphs.ConclusionThe present data suggest that the greater peak amplitude of ICafor SHR myocytes relative to that of myocytes of normotensive rats is due to an increase in current density and enhancement of channel phosphorylation.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo investigate the link between cardiac hypertrophy, elevated blood pressure level and baroreflex impairment, we assessed cardiac baroreflex function in a hypertensive model almost devoid of cardiac hypertrophy, obtained by nitric oxide synthesis inhibition.MethodsThirteen adult male Wistar rats were treated orally withNG-nitro-L-arginine methyl ester (L-NAME, 50mg/kg per 24 h) for 4 weeks. Fifteen control rats received tap water. At the end of the treatment aortic blood pressure was recorded continuously and the baroreceptor–heart rate curve was assessed by bolus injections of phenylephrine and sodium nitroprusside (10 different doses of each).ResultsMean blood pressure was higher in L-NAME rats than in control rats, whereas body weight was similar. Total heart weight and left ventricular weight did not differ between the groups. Cardiac baroreflex was reset in hypertensive rats, as indicated by a rightwards shift of the mean blood pressure-heart rate curve. Its gain was decreased significantly in L-NAME rats, whereas the heart rate range was not different between the two groups.ConclusionL-NAME hypertensive rats exhibit an original impairment of cardiac baroreflex, characterized by a range-independent decreased gain which is not due to cardiac hypertrophy.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo examine the association in Japanese subjects between the salt sensitivity of blood pressure and polymorphic factors.Design and methodsOne hundred and four patients with essential hypertension were classified as salt-sensitive or non-salt-sensitive depending on their blood pressure response to salt restriction. An insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene was examined by detecting analusequence in intron 16. The ACE genotype was classified asII, IDorDDdepending on whether each allele had this sequence. The haptoglobin phenotype was determined by the starch–gel electrophoresis method, and was classified as three phenotypes, 1–1, 2–1 or 2–2 form.ResultsThe response of plasma renin activity to salt restriction was greater in patients with theDDform than in those with other forms, although there were no significant differences in the ratio salt-sensitive: non-salt-sensitive patients among the three ACE genotype groups. However, the ratio was significantly larger in the haptoglobin 2–1 phenotype group than in the 2–2 group.ConclusionsThe salt sensitivity of blood pressure was associated with the haptoglobin phenotype, but was not associated with the ACE genotype. However, the response of plasma renin activity to salt restriction was different according to the ACE genotype.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID