ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo assess whether the pressure-independence of renin release by isolated kidneys of Lyon hypertensive (LH) rats could result from long-term exposure to high blood pressure, sodium retention or an altered regulation of intracellular calcium through L-type voltage operated channels.DesignRenin release was studied in kidneys from LH rats, either controls or chronically (aged 3–7 weeks) treated with hydralazine or deprived of sodium. The influence of L-type calcium channels was studied acutely using a specific activator (BAY K8644) or modulator (verapamil). Lyon low blood pressure (LL) rats served as controls.MethodsKidneys were isolated from LH or LL rats aged 7 weeks and single-pass perfused at three pressure levels: 70, 85 and 160mmHg.ResultsLH rat kidneys differed from LL rat kidneys in having elevated vascular resistances, decreased glomerular filtration rate, pressure natriuresis and pressure-dependent renin release. Hydralazine treatment and sodium deprivation did not significantly modify the pressure-independence of renin release by LH rat kidneys. BAY K8644 (1 × 10-8and 5 × 10-8mol/l) induced significantly greater vasoconstrictor effects in LH than in LL rat kidneys but did not affect the renin release already stimulated by low perfusion pressure. Verapamil (5 × 10-6mol/l) dilated LH more than LL rat kidneys. It did not change the renin release observed at low, but enhanced it at high, perfusion pressure. This effect was more marked in LL than in LH rat kidneys.ConclusionsThe poor stimulation of renin release by low perfusion pressure in LH rat kidneys does not appear to be a consequence of high blood pressure level, sodium retention and alteration in L-type calcium channels. However, results demonstrate that these channels participate in the increased vascular resistances exhibited by LH rat kidneys.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo investigate the mechanism of tissue uptake of renin.DesignAngiotensin peptide formation in tissues is dependent on kidney-derived renin, leading us to hypothesize that tissues possess a mechanism for uptake of renin from plasma.MethodsThe binding of [125l]-labelled renin to membranes prepared from various rat tissues was examined. [125l]-labelled renins were cross-linked to membranes with disuccinimidyl suberate and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by autoradiography.ResultsMesenteric artery membranes bound both [125l]-labelled rat renin and [125l]-labelled mouse submandibular gland renin. Cross-linking experiments showed two bands, one of relative molecular mass approximately 105 000 and the other of approximately 75 000. After taking into account the molecular weight of renin, these bands represent renin-binding proteins of relative molecular mass approximately 70 000 and approximately 40 000, respectively. The highest level of these binding proteins was in the mesenteric artery; lower levels were found in the aorta, lung and renal medulla. Renin-binding proteins were also identified in membranes prepared from cultured rat aortic smooth muscle cells. No binding proteins were identified in the kidney cortex, heart, adrenal capsule, adrenal medulla, periaortic brown adipose tissue, uterus or pituitary. Binding of renin to mesenteric artery membranes was prevented by inhibitors of renin enzymatic activity (H-77 and SQ 30697); this effect of H-77 showed a dose-dependence parallel to the inhibition of renin activity by this compound, suggesting that the binding of H-77 to the active site of renin prevents its binding to the membranes.ConclusionsThese studies provide evidence for a vascular renin-binding mechanism, which may play a role in the generation of angiotensin peptides in vasculature, and may thus be a determinant of blood pressure. Moreover, one of the actions of inhibitors of renin enzymatic activityin vivomay be to prevent the binding of renin to the vasculature.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo establish equivalent doses of four non-steroidal anti-inflammatory drugs (NSAID) in normotensive and hypertensive rats using inhibition of the fall in blood pressure produced by the injection of arachidonic acid as the measure of equivalence.DesignAn experimental study using two rat models of hypertension and their normotensive controls.MethodsTwo rat models of hypertension (spontaneously hypertensive rats and two-kidney, one clip rats) and their normotensive controls were studied. The change in blood pressure after intravenous injection of arachidonic acid was measured in anaesthetized rats. Blood pressure was measured from a carotid artery cannula, attached to a pen-recorder. Dose-response curves for the effect of arachidonic acid were established in each type of rat, then the effects of different doses of four NSAID (indomethacin, piroxicam, naproxen and sulindac) on these responses were measured.ResultsArachidonic acid produced a dose-dependent fall in blood pressure in all rats. However, both types of hypertensive rats sustained a larger fall in blood pressure for a given dose of arachidonic acid than did the normotensive controls. Doses of NSAID were found that inhibited this response in Wistar rats. However, the doses of NSAID that were equivalent in normotensive rats were not equivalent in either type of hypertensive rat; indomethacin had a greater inhibitory effect. As far as could be established, this was not due to differences in the metabolism of the NSAID between normotensive and hypertensive rats.ConclusionsThe arachidonic acid response can be used as a method of establishing equivalent doses of NSAID in normotensive and hypertensive rats. Hypertensive rats appear to be more sensitive to the effects of arachidonic acid than normotensive rats, independent of the model of hypertension. Doses of NSAID that are equivalent in normotensive rats are not equivalent in hypertensive rats. Indomethacin is more effective in attenuating the effect of arachidonic acid, possibly due to actions other than inhibition of cyclo-oxygenase.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo examine renal and intestinal calbindin-D in relation to calcium metabolic changes in three different models of experimental hypertension. Design: Spontaneously hypertensive rats (SHR), hypertension-prone Dahl salt-sensitive (Dahl-S) rats and the Goldblatt two-kidney, one clip rat model of renovascular hypertension were examined.ResultsBoth prehypertensive and hypertensive SHR had significantly lower concentrations of both renal calbindin-D28k and intestinal calbindin-D9k than Wistar control rats. This was accompanied by hypocalcaemia, hypomagnesaemia and increased plasma 1,25(OH)2vitamin D levels. Induction of hypertension in Dahl-S rats reduced intestinal calbindin-D9k and increased plasma levels of 1,25(OH)2vitamin D, while renal calbindin-D28k levels, plasma calcium levels and plasma magnesium levels were unchanged. Renovascular hypertension was associated with a significant increase in the intestinal calbindin-D9k, plasma 1,25(OH)2vitamin D, parathyroid hormone and magnesium levels, while renal calbindin-D28k, plasma calcium and phosphorus levels were unaffected.ConclusionsThese three models of experimental hypertension have clearly demonstrated three separate patterns in the regulation of renal and intestinal calbindin-D, which relate to different alterations of factors involved in calcium and magnesium metabolism. In all three models hypertension was accompanied by a significant increase in plasma concentrations of 1,25(OH)2 vitamin D. Only rats with renovascular hypertension showed increased intestinal calbindin-D9k levels, whereas reduced concentrations were found in the SHR and in the hypertensive Dahl-S rats. This indicates the existence of a resistance at the cellular level to 1,25(OH)2vitamin D affecting the expression of calbindin-D in both SHR and Dahl-S rats.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo investigate whether and how renin-angiotensin inhibition attenuates renal injury seen in salt-induced hypertension in Dahl salt-sensitive (Dahl-S) rats.MethodsDahl-S rats fed a high-salt (4% sodium chloride) diet for 6 weeks were treated with the angiotensin converting enzyme (ACE) inhibitor alacepril or the angiotensin receptor antagonist losartan for 4 weeks. Functional and morphological alterations in the kidney were investigated.ResultsAlacepril decreased systolic blood pressure (SBP). This SBP reduction was associated with the attenuation of cardiac and aortic wall hypertrophy and that of proteinuria and urinary N-acetyl-β-D-glucosaminidase excretion. Kidney injuries, e.g. glomerular, arterial and tubular damage, were improved with alacepril treatment. Losartan decreased SBP to the same extent as alacepril, but neither renal function nor morphological structure was improved as was the case with alacepril. The response of the renal eicosanoid system to alacepril was inadequate, but cyclic GMP excretion, an indicator of nitric oxide formation, was significantly enhanced and lipid peroxidation in the kidney was decreased.ConclusionsThe beneficial effects of ACE inhibition on the renal injury in Dahl-S rats outrange those induced by the receptor antagonism. This might be due to multiple factors including an increased vasodepressor eicosanoid system, enhanced nitric oxide formation and possible inhibition of oxygen radical generation in the injured renal tissues.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo test the hypothesis that an imbalance in intrarenal prostaglandins plays a role in cyclosporin-induced nephrotoxicity.Methods and resultsIndomethacin was given in combination with cyclosporin to healthy volunteers. Cyclosporin alone (10mg/kg twice a day) for 4 days had no effect on effective renal plasma flow (ERPF) and glomerular filtration rate but 4 days of therapy with cyclosporin (10mg/kg twice a day) and indomethacin (50 mg twice a day) in combination resulted in a 37% fall in glomerular filtration rate and a 32% fall in ERPF. This suggests that autoregulatory mechanisms, possibly involving renal prostaglandins, may participate in counteracting the tendency for cyclosporin-induced renal vasoconstriction in humans. Cyclosporin increased systemic blood pressure acutely, and this was not influenced by indomethacin even though indomethacin on its own caused sodium retention. This suggests that, in contrast to the renal vasculature, the systemic vascular response to cyclosporin is neither augmented nor buffered by prostaglandins.ConclusionThe reduction in intrarenal prostaglandins clearly played a key role in the development of cyclosporin-induced renal vasoconstriction, but we could not demonstrate a role for prostaglandins or for sodium retention in the initiation of cyclosporin-induced hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo determine whether soluble E-selectin levels were raised in hypertension and whether such levels correlated with those of von Willebrand factor.DesignForty-five consecutive patients with uncontrolled hypertension (blood pressure >140/90 mmHg) and 33 consecutive patients with controlled hypertension (blood pressure <140/90 mmHg, i.e. normotension) were examined and compared with 40 normotensive age- and sex-matched controls.MethodsLevels of von Willebrand factor and soluble E-selectin were measured by enzyme-linked immunosorbent assay in venous blood serum. Resting systolic (SBP) and diastolic (DBP) blood pressures were measured before venepuncture.ResultsSoluble E-selectin levels were raised in hypertension compared with controls and normotension. The levels of von Willebrand factor were raised in hypertension and normotension compared with controls. In multivariate analysis of all subjects, von Willebrand factor levels correlated with SBP (P< 0.001) and soluble E-selectin level correlated with DBP (P< 0.001), but levels of von Willebrand factor and soluble E-selectin did not correlate. There was no clear relationship between levels of either endothelial cell index or the class of drug therapy used or its dosage.ConclusionsWe suggest that raised levels of soluble E-selectin in hypertension do not indicate endothelial cell injury but may be related to endothelial cell activation. The stimulus for release of soluble E-selectin might be different from that for von Willebrand factor.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID