ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To evaluate the relationship between sudden cardiac death, ventricular arrhythmias and left ventricular hypertrophy in patients with hypertension.Data identification:Epidemiological studies assessing the importance of left ventricular hypertrophy as a risk factor for sudden cardiac death, studies assessing the prevalence of arrhythmias in left ventricular hypertrophy and studies assessing whether there is an electrophysiological substrate in the hypertrophied myocardium for ventricular dysrhythmias.Results of data analysis:Current evidence indicates that left ventricular hypertrophy is a risk factor for sudden cardiac death and that ventricular arrhythmias are more prevalent in hypertensive patients with than in those without left ventricular hypertrophy. However, there is a lack of evidence that these dysrhythmias are important as an underlying mechanism for sudden cardiac death, and there is no clear evidence that the hypertrophied myocardium is, itself, an arrhythmogenic substrate for malignant ventricular dysrthyhmias. One possible mechanism for sudden cardiac death is myocardial ischaemia, either as a consequence of asssociated coronary disease or due to left ventricular hypertrophy, but this remains unproved.Conclusions:There is currently no evidence that the ventricular ectopic activity seen in patients with hypertensive left ventricular hypertrophy is a marker for sudden cardiac death. Clarification of the mechanisms involved in sudden cardiac death will help in selecting appropriate preventive and therapeutic strategies for these patients.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To obtain information about possible pathways mediating the suppression of renin gene expression in the contralateral kidneys of stenosed kidneys.Design:The effects of unilateral renal denervation and of treatment with an angiotensin II antagonist (losartan) on renal renin gene expression were examined in a two-kidney, one-clip model.MethodsRenal renin messenger RNA levels, plasma renin activity, blood pressure and kidney weights were monitored over 10 days in adult male Sprague—Dawley rats with various unilateral reductions of renal blood flow achieved with silver clips of 0.2, 0.3 and 0.4 mm inner diameter.Results:With all the clip sizes used, renin messenger RNA levels increased transiently in the clipped kidneys, the time course and the magnitude of the increase being dependent on the degree of flow reduction. In the contralateral kidneys clipping caused sustained decreases in renin messenger RNA to levels proportional to the clip size. The suppression of renin gene expression in the contralateral kidneys was not related to compensatory growth of the organs nor to changes in plasma renin activity or arterial pressure. Unilateral denervation of the kidney before clipping had no influence on the characteristic increase and decrease in renin messenger RNA in the stenosed and contralateral kidneys, respectively. Treatment of the rats with losartan led to fourfold increases in renal renin messenger RNA levels and to sixfold increases in plasma renin activity in control rats. A 0.3-mm clip did not further increase renin messenger RNA or plasma renin activity in losartan-treated rats but again led to suppression of renin messenger RNA in the contralateral kidney to 50% of the levels found in the clipped kidneys.Conclusions:The results suggest that the suppression of renin gene expression in the contralateral kidneys of stenosed kidneys is not due to compensatory renal growth nor mediated by systemic blood pressure, angiotensin II AT1receptors or renal nerves. We therefore hypothesize that kidneys with reduced perfusion release a humoral factor that acts as a potent inhibitor of renin gene expression.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To test the hypothesis that deuterium oxide (D2O) might induce endothelium-dependent and nitric oxide-mediated vasodilation by altering intracellular calcium concentration ([Ca2+]¡) in vascular endothelial cells.Design:The endothelium-dependent and nitric oxide-mediated regulation of vascular tone by D2O was first examined in perfused rat mesenteric arterial beds. Direct effects of D2O on [Ca2+]¡in cultured vascular endothelial cells were then examined in order to elucidate a cellular mechanism for D2O-induced vasodilation.Methods:Vascular reactivity was assayed by measuring the perfusion pressure of isolated rat mesenteric arterial beds. [Ca2+]¡in cultured bovine and rat vascular endothelial cells was measured with the fura-2 fluorescence technique.Results:D2O relaxed precontracted rat mesenteric arterial beds with an intact endothelium. This effect of D2O was either inhibited by Nco-nitro-L-arginine (a nitric oxide synthase inhibitor) or eliminated by the removal of endothelium. In cultured bovine aortic, rat aortic, and rat tail artery endothelial cells, D2O induced a biphasic increase in [Ca2+]¡, with a characteristic initial transient increase followed by various patterns of sustained [Ca2+]¡increase. The sustained phase was entirely dependent on the extracellular calcium entry.Conclusions:A direct effect of D2O on [Ca2+]¡in vascular endothelial cells may be responsible for the endothelium-dependent, presumably nitric oxide-mediated, vasodilation induced by D2O in precontracted vessels. From these results new mechanisms can be explored for the antihypertensive effect of D2O and new avenues can be developed to study the functional integrity of the endothelium-dependent regulation of the vascular tone.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To determine the roles of vasopressin, the renin—angiotensin system and sex in the pathogenesis of salt-sensitive hypertension in the Dahl rat.Design:The effects of 12 days' treatment with a non-peptide, orally effective V1antagonist (OPC-21 268) and captopril, individually or together, were compared in male and female Dahl salt-sensitive rats after 10 days on a high-salt diet.Methods:OPC-21 268 was given in the food, and captopril was administered with osmotic pumps implanted subcutaneously.Results:Systolic blood pressure (SBP) reached a higher level in untreated males than in untreated females. V1blockade in males prevented any further increase in SBP during the first week of treatment, but SBP rose thereafter towards the levels found in the untreated males. In females OPC-21 268 had no effect. In males captopril prevented any further increase in SBP. There was no effect of captopril in females during the first week of treatment, but SBP fell to pretreatment levels during the second week. Combined treatment with OPC-21 268 and captopril in males had a smaller antihypertensive effect than either drug alone. In females combined treatment prevented any further increase in SBP.Conclusions:These findings suggest that both vasopressin and the renin—angiotensin system contribute to the pathogenesis of Dahl salt-sensitive hypertension, but that other factors, possibly including the sympathetic nervous system, are also involved. Sex also affects the severity of this form of hypertension and influences the relative roles of vasopressin and the renin—angiotensin system. It is likely that the gonadal steroid hormones modulate the activity of the pathogenetic factors in this form of hypertension at a central or peripheral level.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To determine whether immunoreactive tissue kallikrein levels in cerebrospinal fluid (CSF) of spontaneously hypertensive rats (SHR) and desoxycorticosterone acetate (DOCA)—salt-treated hypertensive rats are elevated compared with normotensive Wistar—Kyoto (WKY) and Sprague—Dawley rats.Design:The present study was designed to test the hypothesis that the activity of the brain tissue kallikrein—kinin system is enhanced in hypertensive states.Methods:Age-matched 18- to 19-week-old SHR and WKY rats, and Sprague—Dawley rats treated for 6 weeks either with 2 mg/kg per day DOCA subcutaneously and 0.9% saline in the drinking water, or with vehicle and tap water to drink, were studied. CSF was collected from a cannula inserted into the cisterna magna, and was frozen until the tissue kallikrein in the samples was measured by radioimmunoassay. Arterial pressure in the SHR and WKY rats was measured directly via a cannula inserted in the femoral artery or by tail-cuff plethysmography.Results:In adult 18- to 19-week-old SHR the CSF kallikrein concentration was higher than in WKY rats. The CSF flow rate in SHR was also higher than in WKY rats. The rate of appearance of kallikrein in the CSF of SHR was twice that in WKY rats. Moreover, CSF kininogenase activity in SHR was significantly higher than that in age-matched WKY rats. In DOCA—salt hypertensive rats the CSF kallikrein concentration was higher than in vehicle-treated control rats. Acute elevation of blood pressure with a 120-min intravenous phenylephrine infusion did not change the CSF kallikrein concentration in 50 rats compared with vehicle-treated control rats. This is the first study to quantitate immunoreactive tissue kallikrein in the CSF of rats and to show elevated levels of CSF kallikrein in hypertensive rats compared with normotensive rats.Conclusion:The present data suggest that higher brain kallikrein activity in hypertensive rats may play a role in the development of elevated blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To investigate the involvement of the heat-shock protein 70 (hsp70) locus, located in the rat major histocompatibility complex (RT1), in hypertension of the spontaneously hypertensive rat (SHR). Previous studies have shown abnormal expression of hsp70 in the SHR and an association of the SHR hsp70 allele with increased blood pressure in recombinant inbred strains derived from a cross of SHR with Brown—Norway rats.Design:SHR were crossed with normotensive Wistar—Kyoto (WKY) rats to produce a large cohort of F2rats segregating for blood pressure and hsp70 alleles. Two hundred and thirty-three rats were maintained on a normal-salt diet and 167 were put on a high-salt diet (1% sodium chloride in drinking water) from 16 to 26 weeks of age.Methods:Blood pressure was measured indirectly at 12, 16 and 20 weeks of age in rats on the normal-salt diet and at 16 (pre-salt), 18 and 20 weeks in rats on the high-salt diet. Both groups had direct conscious blood pressure measurements at 25-26 weeks of age. Genotyping was carried out for a BamH1 polymorphism in the hsp70 gene by Southern blotting.Results:The hsp70 genotype had no effect on any of the blood pressure measurements in rats on either diet.Conclusions:We find no evidence of linkage between the hsp70 gene locus, and by implication other genes located within the rat RT1 complex, and blood pressure in our cross of SHR and WKY rats.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:Linkage studies have shown that the gene locus for angiotensin converting enzyme (ACE) is associated with the expression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). We tested the hypothesis that the conversion of angiotensin I (Ang I) to angiotensin II (Ang II) in blood vessels is elevated in SHRSP.Design:We measured the conversion rate of Ang I to Ang II during one pass through an isolated resistance vessel bed. We used the same substrains of SHRSP and Wistar—Kyoto control rats (WKY) that had been employed in the earlier linkage studies.Methods:Isolated hindquarters from young and adult (10- to 12- and 36- to 38-week-old) rats were perfused with an artificial medium and then infused with Ang I at 0.5 and 2pmol/ml. Ang I and II were measured with high-performance liquid chromatography and radioimmunoassay in hindquarter effluent and in blank control channels. Conversion and extraction rates were calculated from angiotensin levels in hindquarter and blank perfusion channels, respectively.Results:The conversion rates of Ang I to Ang II did not differ between SHRSP and WKY in young or in adult rats. Captopril completely abolished the formation of Ang II in all groups of rats. During infusion at the higher dose of Ang I, the extraction of Ang I was significantly decreased in SHRSP compared with WKY.Conclusions:Our results are consistent with the notion that the metabolism of angiotensin is decreased in spontaneously hypertensive rats. However, we found no support for the hypothesis that vascular ACE is responsible for high blood pressure in SHRSP. These findings suggest that other genes close to the ACE locus or the hyperexpression of the enzyme in other areas may contribute to hypertension in these rats.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:Nerve growth factor (NGF) is a neurotrophic protein which acts on peripheral sympathetic nerves. Elevated NGF in vascular tissues of young spontaneously hypertensive rats (SHR) has been reported. The aim of the present study was to compare the amount of NGF secreted from cultured vascular smooth muscle cells (VSMC) and mesenteric artery and thoracic aorta segments from SHR and Wistar—Kyoto (WKY) rats.Methods:VSMC prepared by the enzyme digestion method from the thoracic aortic media of 14-week-old SHR and age-matched WKY rats were subcultured in Dulbecco's modified Eagle's medium containing 10% fetal calf serum. Segments of mesenteric artery and thoracic aorta from 4-week-old SHR and age-matched WKY rats were similarly cultured. The NGF content in conditioned medium was measured using an enzyme immunoassay. The protein content of VSMC was measured by the Lowry method.Results:Total NGF content in the cell culture medium was increased during an exponential growth phase and then gradually decreased during a quiescent phase in both rat strains. There were no significant differences in the levels of NGF secreted from mesenteric artery and thoracic aorta segments between the SHR and WKY rats. The differences in cellular protein content between SHR and WKY rats were very small.Conclusions:In contrast to the reports of increased NGF in SHR tissues, our data demonstrate that NGF secretion was lower in VSMC from SHR, and was equivalent in mesenteric artery and thoracic aorta segments from SHR and WKY rats. We have no clear explanation for these observations, but the present results indicate that upregulation of NGF in SHR tissues is not responsible for a simple enhancement of NGF synthesis in VSMC, and suggest a breakdown of the regulatory mechanism or mechanisms of NGF gene expression in SHR tissues.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To characterize an ATP-sensitive K+channel at the single-channel and tissue level in the vascular smooth muscle of normotensive and genetically hypertensive rats.Methods:Age- and sex-matched Wistar—Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) were used. Patch-clamp single-channel recording was used to measure K+channel activity in dissociated tail artery cells. The effect of the K+channel-opener diazoxide and the specific ATP-sensitive K+channel antagonist glyburide on isometric force development in isolated tail artery strips was determined by a standard muscle bath technique.Results:The concentration of ATP that caused half-maximal reduction in channel activity was greater in the SHRSP than in the WKY rats. Tail artery strips and cells from SHRSP were more sensitive to the effect of diazoxide on relaxation and channel activity, and less responsive to the effect of glyburide, than were those from WKY rats.Conclusions:The decreased ATP sensitivity of this K+channel may partly compensate for the increased vascular reactivity in hypertension, and the change in this property of the channel may be responsible for the altered sensitivity to diazoxide and glyburide in SHRSP.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID