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

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo identify the site of the increased expression of the SAgene in the kidney of the spontaneously hypertensive rat (SHR) compared with the Wistar-Kyoto (WKY) rat.MethodsIn situ hybridization of SHR and WKY rat kidney sections with a radioactively labelled rat SAcomplementary DNA probe.ResultsCompared with WKY rat kidney sections, the probe bound intensely to the SHR renal cortex. Binding was sensitive to pretreatment of the section with RNAase A. Microscopic examination after autoradiography showed the increased signal in the SHR to be localized over proximal tubules. Background signal was observed over glomeruli, distal tubules, interlobular arteries and afferent arterioles.ConclusionsThe localization of the increased expression of the SAgene in the SHR kidney compared with the WKY rat kidney to the proximal tubule suggests that it might influence blood pressure through effects on tubular function. Several differences in proximal tubular function have already been described between the SHR and WKY rat, and the relationship of these to tubular SAgene expression now need to be investigated. However, in the absence of any known functions for the SAgene product it is also possible that it might act through entirely novel, still undefined mechanisms.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo determine whether α1- or β-adrenergic receptors are altered during regression of cardiac hypertrophy produced by antihypertensive agents.Design and methodsCardiac hypertrophy was induced in rats by aortic banding. After 6 weeks banding the rats were treated with an angiotensin converting enzyme (ACE) inhibitor (enalapril), an α1-adrenergic antagonist (bunazosin) or a β-adrenergic antagonist (propranolol) for 6 weeks to induce regression. The numbers of α1- and β-adrenergic receptors, haemodynamics, tissue noradrenaline content and tissue ACE activity were measured.ResultsRegression of cardiac hypertrophy occurred after treatment of aortic banded rats with a high dose of enalapril, bunazosin or propranolol, and was accompanied by a reduction in systolic blood pressure. The number of α1- or β-adrenergic receptors was unchanged by propranolol treatment, but the number of α1-adrenergic receptors was increased in the hearts of rats treated with bunazosin. A low dose of enalapril (3 mg/kg body weight) caused regression of hypertrophy without a concomitant reduction in blood pressure, and decreased the number of α1-adrenergic receptors. The dissociation constants for α1- and β-adrenergic receptors were not different among the experimental groups, and the positive derivatives of left ventricular pressure was unaltered in rats treated with a low dose of enalapril but was reduced by the other drugs.ConclusionOf the three drugs tested, only the low dose of enalapril affected adrenergic receptors during regression of cardiac hypertrophy, causing a decrease in α1-adrenergic receptor number without a reduction in blood pressure. This effect may be explained by non-haemodynamic actions of the ACE inhibitor enalapril, probably by modulation of peripheral sympathetic activity.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

IntroductionThe spontaneously hypertensive rat (SHR) has been shown to possess elevated efferent sympathetic nerve activity, and renal denervation delays the development of hypertension in this genetic strain. Evidence that the renal sympathetic nerves have direct effects on tubular function suggests that one of the mechanisms for increasing arterial pressure in the SHR might involve neurally mediated sodium retention.Aims and methodsThe present study examined the relationships between renal sympathetic tone, daily sodium balance and the development of hypertension in SHR over a 4-week period. Conscious, unrestrained, 7-week-old SHR with innervated or denervated kidneys were placed on a fixed sodium intake by intravenous infusion (5.72 μmol/day per 100g body weight). Urinary sodium excretion was determined once a day for 28 consecutive days; systolic blood pressure (SBP) and body weight were monitored twice a week.ResultsRenal denervation delayed the onset of and retarded the development of hypertension. Despite the difference in SBP, daily sodium balance was equal in the innervated and the denervated SHR. The positive sodium balances exhibited by both groups are attributed to the rapid growth observed during the time course of the experiment. The growth rate was also similar in the two groups.ConclusionThe present data indicate that, although the renal nerves may mediate enhanced transient tubular sodium reabsorption, sodium retention does not contribute directly to the development of hypertension in the SHR. Rather, it appears that the elevation of arterial pressure might occur as a requirement to excrete excess sodium and thus maintain a daily sodium balance.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo test the hypothesis that impaired Ca2+recycling by the sarcoplasmic reticulum Ca-ATPase contributes to augmented force development in arteries from stroke-prone spontaneously hypertensive rats (SHRSP).MethodsForce development to caffeine (0.3–30 mmol/l) in the absence of extracellular Ca2+was compared in aortic strips from SHRSP and Wistar-Kyoto (WKY) rats. In another protocol the strips were rinsed at the peak of contraction to caffeine (20 mmol/l) and subsequently restimulated with the alkaloid. The second response, dependent on recycled Ca2+, was used as a measure of sarcoplasmic reticulum function. A third protocol evaluated caffeine-induced contractions after Ca2+depletion and reloading. In these latter experiments the effects of thapsigargin, an inhibitor of the sarcoplasmic reticulum Ca-ATPase, and ryanodine, an activator of sarcoplasmic reticulum Ca2+release channels, were used to evaluate Ca2+buffering. Finally, unidirectional45Ca2+ influx was measured.ResultsContractions to caffeine (0.3–30 mmol/l) were larger in SHRSP aortic strips than in WKY rat strips. After a rinse at the peak of the initial response to caffeine, SHRSP segments contracted more when challenged a second time. Thapsigargin (0.3–10 μmol/l) caused a concentration-dependent contraction during Ca2+loading that was greater in SHRSP than in WKY rat strips, and a concentration-dependent inhibition of caffeine-induced contraction with similar median inhibitory concentrations in the two groups. Ryanodine did not cause contraction during Ca2+loading, but caffeine-induced contractions were reduced after ryanodine treatment in both groups.45Ca2+ influx was increased in SHRSP aortic segments.ConclusionsThe greater force development to caffeine in SHRSP aortic strips probably reflects a greater storage of activator Ca2+in the sarcoplasmic reticulum. On the basis of the pharmacological properties of thapsigargin and ryanodine, it appears that the larger store is caused by enhanced Ca2+influx across the sarcolemma rather than by recycling of Ca2+by sarcoplasmic reticulum Ca-ATPase. Experiments evaluating the secondary response to caffeine also support the interpretation that recycling of activator Ca2+into the sarcoplasmic reticulum does not explain the augmented force development in SHRSP aortic segments.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveA reduced number of nephrons, whether acquired or congenital, as has been observed in certain inbred rat strains, may lead to systemic hypertension. The present study estimated the total number of glomeruli and mean glomerular size in kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats.MethodsUnbiased stereological methods were used on immersion-fixed kidneys from 12-week-old male SHR (n = 9) and age-matched WKY rats (n = 11).ResultsThe total number of glomeruli was significantly reduced in the SHR compared with in the WKY rats. Sclerotic glomeruli were not found in either group. No significant difference in mean glomerular volume was observed, but the total glomerular volume was reduced by 25% in the SHR compared with in the WKY rats.ConclusionSHR have fewer glomeruli than WKY rats, but of similar size, resulting in a reduced total glomerular volume in adult SHR. These findings are consistent with the hypothesis that the kidney plays an important role in the pathogenesis of genetic hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveThe present study investigated the antagonism of the amino-terminal heptapeptide fragment of angiotensin II {[des-Phe8]-angiotensin II; Ang(1–7)} to angiotensin II (Ang II) both in vitro in rabbit aortae and in vivo in rats.Methods and resultsIn rabbit isolated endothelium intact aortic rings Ang(1–7) caused a concentration-related rightward displacement of the Ang II curve and depressed the maximum response to Ang II. By applying the data to a Schild plot an apparent pA2 of 5.5 was calculated. This depression of maximum response could be reversed by co-incubation of Ang(1–7) with the competitive angiotensin antagonist losartan. Ang(1–7) had no effect on the contractile responses of several other agonists. Intravenous infusion of 10 or 100 μg/kg per min Ang(1–7) had no effect on the resting blood pressure in the anaesthetized rat but inhibited Ang II-induced pressor responses.ConclusionThe present results show that Ang(1–7) is a specific non-competitive antagonist of Ang II at type 1 angiotensin II receptors.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID