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:To investigate whether the reported insulin-like properties of vanadate may have hypertensinogenic actions in Sabra rats.Design:Comparison of [3H]-deoxyglucose muscle uptake as well as blood pressure and its response to acute volume expansion and pressors infusions in 16 vanadate-treated (VT) and 12 control rats.Methods:Rats drank either tap water or 0.2 g/l vanadate for 4 weeks. A trace amount of [3H]-deoxyglucose was administered intravenously to evaluate its plasma half-life and tissue uptake, intra-arterial blood pressure was recorded in response to acute intravenous saline (4 ml/100 g body weight) and to incremental bolus injections of noradrenaline and angiotensin II (Ang II).Results:Skeletal muscle uptake of [3H]-deoxyglucose was significantly higher in VT than in control rats. There was no difference between the blood pressure of VT or control rats; however, 2 h after saline loading the mean intra-arterial blood pressure was significantly higher in VT than in control rats. The Ang ll-induced blood pressure rise was also significantly higher in VT rats.Conclusion:The insulin-like activity of vanadate may be associated with salt-sensitive hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objectives:Previous studies on multicellular preparations have shown that hypertrophied cardiac muscle from the spontaneously hypertensive rat (SHR) has a prolonged action potential. The first aim of the present study was to determine whether the action potential of isolated left ventricular myocytes was similarly prolonged and to study the underlying membrane currents that might be responsible. The second aim was to evaluate the L-type calcium current amplitude of SHR myocytes, as we have recently shown that they have an increased contraction and an increase in the calcium trigger entering via the L-type calcium channel might be one possible mechanism for this.Methods:The electrophysiological characteristics of left ventricular myocytes isolated from the SHR were compared with those from normotensive control rats. Action potentials were recorded with microelectrodes. Cells were voltage-clamped and the membrane currents elicited by steps to different potentials were analysed. Blockers of potassium and calcium currents were used to reveal the contribution made by these currents to net membrane currents.Results:SHR myocytes had prolonged action potentials. The action potential duration of SHR myocytes at 90% repolarization was found to be longer, although at 20% and 50% repolarization no difference was found. There was no difference in the resting membrane potential between SHR and control myocytes. Using a voltage clamp we studied the L-type calcium current and potassium currents. The major change in SHR myocytes was a decrease in the magnitude (normalized to the membrane capacitance) of the inward rectifier potassium current elicited by negative potentials. There was no detectable difference in either the transient outward or delayed rectifier potassium currents. We also found no difference in the magnitude, time course or voltage dependence of L-type calcium current in hypertrophied SHR myocytes.Conclusions:First, the action potential of SHR myocytes was prolonged compared with control myocytes. Secondly, the main change in SHR myocytes was that pulses to negative potentials elicited a lower inward rectifier potassium current. A reduction in the density of inward rectifier channels might play a role in prolonging the SHR action potential, since a lower outward repolarizing current will flow through inward rectifier potassium channels during the SHR action potential repolarization. Thirdly, there was no difference in L-type calcium current density or time course between SHR and control myocytes. Thus, a change in L-type calcium current probably plays no role in causing the prolonged SHR action potential or the increased contraction of hypertrophied SHR ventricular myocytes. Finally, the prolonged action potential in SHR myocytes may itself be one factor responsible for the increased contraction of these cells.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:The present study was designed to examine, using isolated preparations of thoracic aorta, the effects of artificial phosphatidylcholine vesicles (liposomes) on vascular endothelium-dependent responses in spontaneously hypertensive rats (SHR) compared with those in Wistar—Kyoto (WKY) normotensive rats.Design:Phosphatidylcholine liposomes, which possess the ability to repair the plasma membrane of living cells, were used in these experiments.Methods:Liposomes were prepared from egg phosphatidylcholine. A suspension of lipid was subjected to ultrasound treatment at 20°C at a frequency of 44 kHz for 45 s. The contraction of vascular smooth muscle was recorded using a force-displacement transducer coupled with a physiograph.Results:It was shown that aortic smooth muscle from SHR demonstrated a loss of endothelium-dependent relaxation in acetylcholine (10-6mol/l) compared with WKY rat aortic smooth muscle. Liposomes in a concentration of 100-125 µg/ml restored these endothelium-dependent responses more effectively than t-arginine (10-5to 10-4mol/l), which is known to be a precursor of endothelium-derived relaxing factor (EDRF). This effect was not observed in denuded aortic rings, and liposomes lost their ability of repairing endothelium-dependent vascular relaxant responses in the presence of methylene blue (5 x 10-5mol/l), which inhibits soluble guanylyl cyclase activation by nitric oxide (NO), and Nco-nitro-L-arginine (t-NNA, 5 x 1O-5to 10-4mol/l), a potent and selective inhibitor of NO synthase.Conclusion:The present results suggest that the loss of vascular endotheliumdependent responses in SHR may be, at least partly, due to endothelial cells membrane damage, and that the phosphatidylcholine liposomes can repair the function of endothelial cells and restore synthesis or release, or both, of EDRF in hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To investigate whether the differences in the growth properties between vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats depend on the type and nature of the growth factor.Design:The growth characteristics of VSMC from SHR and WKY rats were compared in the presence of different growth factors. These were related to growth factor receptor expression on the VSMC.Methods:Growth rates, cell densities at which VSMC become quiescent and [3H]-thymidine incorporation into DNA were examined in VSMC from SHR and WKY rats following exposure to epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) or the three isoforms of platelet-derived growth factor (PDGF-AA, PDGF-AB and PDGF-BB). Receptor expression (receptor binding and Northern analysis) for these growth factors was also examined on VSMC from the two strains.Results:VSMC from SHR exposed to the individual growth factors exhibited growth rates higher than those from WKY rats. For EGF, bFGF, PDGF-AB and PDGF-BB there was no difference in the sensitivity of VSMC to stimulation of [3H]-thymidine incorporation between the strains. In contrast, VSMC from SHR exhibited significantly increased sensitivity to the mitogenic effects of PDGF-AA. VSMC from SHR exposed to PDGF-BB or EGF proliferated and then became quiescent at densities approximately 50 and 200% higher, respectively, than those from WKY rats. In contrast, in the presence of bFGF, proliferating VSMC from WKY rats became quiescent at densities approximately 20% higher than those from SHR. Scatchard analysis of [125l]-labelled growth factor binding to VSMC from the two strains revealed similar receptor numbers and dissociation constants for all growth factors. Steady-state messenger RNA levels for the different receptors were also similar and could not account for the enhanced growth rates of VSMC from SHR.Conclusion:The rate and magnitude of the proliferative response elicited in VSMC cultures from SHR and WKY rats is critically dependent on the nature of the growth factor stimulus.

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 effect of L-arginine administration on patients with essential and secondary hypertension by measuring haemodynamic parameters, neuroendocrine hormones and indicators of nitric oxide (NO) release.Design:Ten patients with essential hypertension and six with secondary hypertension (three with renovascular hypertension and three with primary aldosteronism) were enrolled in the study.Methods:L-Arginine was administered intravenously to the hypertensive patients. During L-arginine administration, blood pressure, heart rate, cardiac output and neuroendocrine hormones such as catecholamines, plasma renin activity and plasma aldosterone were measured. To examine whether L-arginine administration increases NO production, indicators of NO release in vivo such as plasma cyclic GMP, plasma citrulline and urinary excretion of nitrite and nitrate were measured simultaneously.Results:During administration, mean arterial pressure decreased, heart rate increased, cardiac output increased and total peripheral resistance decreased. The indicators of NO release increased simultaneously during administration. Catecholamine and plasma renin activity, rather than increasing in response to L-arginine-induced hypotension as expected, showed no significant changes except in patients with renovascular hypertension. In all patients plasma aldosterone levels decreased significantly in response to L-arginine administration, regardless of basal plasma renin activity and aldosterone levels.Conclusions:These results suggest that exogenous L-arginine produces a vasodilatory effect by increasing NO production and that L-arginine, or released NO, modulates the release of neuroendocrine hormones in hypertensive subjects.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objectives:Whether muscle sympathetic nerve activity (MSNA) is increased in young subjects with mild essential hypertension has not been firmly established, and the potential haemodynamic correlates of any such increase have not been specifically investigated. The objectives of this study were to quantitate MSNA from the peroneal nerve of young subjects with mild hypertension, to determine the haemodynamic and neurohumoral correlates of sympathetic vasoconstrictor nerve traffic in such subjects, and to document the stability of these observations.Design:Twelve young untrained subjects with mild essential hypertension (mean age 31 years, average clinic blood pressure 151/95 mmHg) and 11 age- and weight-matched normotensive subjects were studied on two sessions, at least 1 month apart, at the same time of day and under identical laboratory conditions.Methods:Blood pressure (non-invasive), microneurography (MSNA; peroneal nerve), cardiac output and calculated total peripheral resistance (echocardiography and continuous-wave Doppler) and calf blood flow and resistance (plethysmography) were recorded during supine rest and assessed for condition and study order effects by two-way analysis of variance. Reproducibility of MSNA was quantified by the standard deviation of the mean difference (SDD) between the values obtained on the two study days.Results:Muscle sympathetic nerve burst frequency and incidence, calf vascular resistance and cardiac output and index were significantly higher in hypertensive subjects, whereas heart rate, total peripheral resistance, plasma noradrenaline and plasma atrial natriuretic factor concentrations were similar in the two groups. There was no study order effect, in either group, on mean values for MSNA or these haemodynamic variables, but the SDD (day 1-day 2 variation) in muscle sympathetic burst frequency was significantly greater in hypertensive subjects.Conclusions:Mild essential hypertension in young subjects can be characterized by augmented MSNA as measured from the peroneal nerve, greater between-session variation in sympathetic burst frequency (but no study order effect), and increased calf vascular resistance and cardiac output. These sympathoneural and haemodynamic alterations are potential mechanisms of primary hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To assess the effects of 80 mmol/day reduction in dietary sodium intake on clinic and 24-h ambulatory blood pressure in elderly hypertensive subjects.Design:Double-blind, randomized, placebo-controlled, crossover trial lasting 10 weeks, following a 4-week run-in period. Subjects: Seventeen untreated subjects with essential hypertension [systolic blood pressure (SBP) ≥160mmHg and/or diastolic blood pressure (DBP) ≥ 95 mmHg], mean age 73 years (range 66-79).Interventions:Subjects had clinic blood pressure and 24-h urinary electrolyte excretion measured while on their normal diet. Following a 4-week run-in period on a reduced-sodium diet (80-100 mmol/24h) subjects entered a 10-week crossover trial of 80mmol/24h sodium supplement or matching placebo while continuing on the reduced-sodium diet.Main outcome measures:The within-patient change in clinic and 24-h ambulatory blood pressures at the end of each intervention period.Results:Mean urinary sodium excretion at the end of the run-in phase rose during the high sodium intake phase and was reduced significantly at the end of the low sodium intake phase. There was a significant reduction in clinic supine SBP between the high- and low-sodium phases. There was no significant change in standing SBP, supine or standing DBP or pulse rate between phases. There was a non-significant reduction in mean 24-h SBP and DBP on the low sodium intake. At the end of the low-sodium phase there was a significant increase in plasma renin activity and aldosterone levels, but no change in plasma electrolytes.Conclusions:Overall, moderate sodium restriction in elderly hypertensives resulted in a significant fall in clinic supine SBP only, although marked differences in intersubject responses were found. Moderate sodium restriction may be of benefit in only some elderly hypertensive subjects as part of a non-pharmacological regimen for blood pressure reduction.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID