ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo evaluate the significance of locally synthesized renin in the pathogensis of hypertension, we investigated modulation of the renin gene expression in extrarenal tissues.DesignExpression levels of renin messenger (m)RNA in various tissues were determined in the genetically hypertensive rats and their control strains. Effects of salt, captopril and clonidine upon renin gene expression were also investigated.MethodsDue to the very low expression level of renin mRNA in extrarenal tissues, a competitive polymerase chain reaction method of assessment was applied. Total RNA from various tissues combined with a synthetic deletion-mutated renin RNA were reverse-transcribed and the resultant complementary DNA mixtures were amplified in one reaction in which the same primers were used.ResultsExpression levels of the renin mRNA in various parts of the central nervous system of 4-week-old spontaneously hypertensive rats were approximately twofold higher than those of age-matched Wistar-Kyoto rats and expression levels in the brain were positively modulated by the administration of either captopril or clonidine.ConclusionsThe importance of the brain renin angiotensin system in the pathogenesis of hypertension in spontaneously hypertensive rats was strongly suggested.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectivesTo evaluate differences in left ventricular structural changes related to different hemodynamic patterns.DesignOne-kidney, one clip (1K1C; volume-dependent hypertension) rats were two-kidney, one clip (2K1C; high-resistance hypertension) to determine whether these two types of Goldblatt rats showed different types of left ventricular adaptation.MethodsM-mode echocardiography was used to study 28 2K1C and 19 1K1C Wistar rats 8 weeks after surgery and 55 age-matched control animals.ResultsSystolic blood pressure was equally high in the two models; the 1K1C rats had a larger left ventricular chamber and normal plasma renin activity (PRA), whereas in the 2K1C rats PRA was increased and the left ventricular chamber was normal. The atrial natriuretic factor was significantly increased only in the 2K1C rats and was related to PRA. The left ventricular mass index was increased in both models, but more in the 1K1C than the 2K1C ratsConclusionsIn both models the degree of left ventricular hypertrophy was associated with the interacting effects of the hemodynamic component superimposed on the primary hemodynamic pattern (i.e. blood pressure as an expression of pressure overload in the primarily volume-dependent 1K1C rats and the left ventricular chamber size as an expression of volume overload in the high-resistance 2K1C rats). The interaction between pressure and volume increased the left ventricular wall thickness in both models, with additional chamber enlargement in the 1K1C rats. In these rats, the increase in left ventricular mass was more pronounced due to the greater volume load on the heart.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveThis paper examines the hypothesis that aberrations in vascular smooth muscle univalent ion transport systems play an important role in the pathogenesis of hypertension.DesignBaseline Na+-K+pump and Na+-K+-2CI∼ co-transport activities and the regulation of these ion transport systems by angiotensin II and second messenger molecules have been studied in cultured aortic smooth muscle cells (VSMC) from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).MethodsIon transport was studied using isotopic univalent cations (86Rb and22Na).ResultsBaseline Na+- K+pump activity was comparable between SHR- and WKY-derived VSMC. Baseline Na+-K+-2CI∼ and K+-CI∼∼ co-transport activity as well as K+leakage were significantly greater in SHR VSMC. Baseline Na+-K+-2CI∼ co-transport was sensitive to inhibition by forskolin and ethyleneglycol-bis-(β-amino ethylester)-N,N,N′,N′-tetraacetic acid, whereas cyclic guanosine monophosphate and phorbol 12-myristate, 13-acetate had no effect. Angiotensin ll-stimulated Na+-K+-2CI∼∼ co-transport activity did not differ between WKY and SHR VSMC. Angiotensin II increased Na+- K+-pump activity to a significantly greater extent in SHR VSMC. The stimulatory effect of angiotensin II upon Na+-K+pump activity was reduced under Na+-free buffer conditions and in the presence of the Na+-H+exchange inhibitor, ethylisopropyl amiloride. Na+-K+pump activity was also stimulated by the protein kinase C activator, phorbol 12-myristate, 13-acetate, and this was completely inhibited under Na+-free buffer conditions.ConclusionsSHR VSMC exhibit anomalous Na+-K+-pump and Na+-K+-2Cl-co-transport activities. The influence of these univalent ion transport systems upon cellular Na+and Ca2+homeostasis invoke their participation in the pathogenesis of hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objective and designThe present study was designed to determine whether increases in sodium concentration in the cerebrospinal fluid (CSF) play a role in the augmented hypertension induced by long-term salt loading in spontaneously hypertensive rats (SHR), and whether the enhanced arginine vasopressin (AVP) activity and/or the sympathetic nervous system contribute to the increased hypertension.MethodsMeasurement of CSF sodium concentration and systolic blood pressure of SHR during salt loading, with or without uninephrectomy, for 7 weeks. Assessment of the hypotensive response to AVP antagonist and hexamethonium, and the plasma levels of AVP and catecholamines.ResultsSalt-loading for 7 weeks led to a gradual increase in hypertension in SHR. CSF sodium in the SHR was increased by a combination of uninephrectomy and saline-drinking after 7 weeks, but not 3 weeks. The difference in mean arterial pressure (MAP) among the three groups of SHR disappeared after the combined blockade of AVP and sympathetic nervous function. CSF sodium correlated with both resting MAP and the fall in MAP induced by the combined administration of AVP antagonist and hexamethonium. Plasma levels of AVP were significantly elevated in the salt-loaded uninephrectomized SHR. Plasma catecholamines did not change significantly as a result of treatment.ConclusionsWe tentatively conclude that chronic salt loading may lead to an increase in CSF sodium, in association with an enhancement of sympathetic nerve activity and, to some extent, of AVP release. These events may explain the augmented development of hypertension in SHR.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

IntroductionMyosin isozymes have been known to become altered during the development and regression of myocardial hypertrophy, but the mechanism by which the shifting takes place is not known. The present paper describes the effects of antihypertensive drugs, with a known mechanism of action, upon myocardial mass, blood pressure and myosin isoforms in spontaneously hypertensive rats (SHR).MethodsSHR were treated with antihypertensive drugs and their blood pressure, myocardial mass and myosin isoforms determined.ResultsA shift of myosin isoform from the V3to the V1type and normalization of myocardial hypertrophy were seen in rats treated with captopril but not in those treated with diuretics. Clonidine and guanethidine increased the V3form in association with moderate control of blood pressure and no change in myocardial mass. Treatment with a β-blocker regressed hypertrophy, controlled hypertension but increased the V3form. Treatment with minoxidil normalized blood pressure, increased cardiac mass and increased the V3type.ConclusionsTreatment with different antihypertensive drugs does not cause similar types of shifts in myosin isoform and has divergent effects upon blood pressure and heart weight. Furthermore, there is no correlation between myocardial mass, blood pressure and myosin isozyme shifts. We conclude that factors other than blood pressure, myocardial mass and catecholamines modulate the shifting of myosin isoforms. Since captopril had a greater remedial effect upon myosin isoforms in our study than the more commonly used agents, we recommend that the current criteria for selection of antihypertensive drugs and the relation between those drugs and cardiac function be re-evaluated.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveThe present study was carried out to examine the involvement of dopamine in the pressure-natriuresis phenomenon which has been postulated as a major regulator of extracellular fluid volume and thereby arterial pressure.DesignDopaminergic modulation of the pressure-natriuresis response was studied in the innervated and denervated rat kidney, to allow a distinction between the effects of neural and extraneural dopamine.MethodsThe pressure-natriuresis response was studied in anesthetized Sprague-Dawley rats, in which neural and hormonal influences on the kidney were fixed by denervating the kidney and by intravenous infusion of aldosterone, hydrocortisone, vasopressin and norepinephrine. The innervation to the kidney remained intact in some experiments with the selective dopamine-1 antagonist SCH 23390. Urinary excretion of dopamine during the pressure-natriuresis response was also examined in the innervated and denervated rat kidney.ResultsAlthough infusion of dopamine at a dose of 2 (μ/kg per min had no effect on the pressure-natriuresis response in rats in which neural and hormonal influences on the kidney were fixed, the slopes of the relations between urine flow, sodium excretion and mean arterial pressure in rats given 10 μ/kg per min dopamine were significantly greater than those found in the control rats. Renal plasma flow increased significantly in the dopamine-treated rats whilst glomerular filtration rate did not differ between the control and dopamine-treated rats. The dopamine-induced increase in the slope of pressure-natriuresis relationship and renal plasma flow were completely blocked by 0.5 μ/kg per min SCH 23390. However, infusion of SCH 23390 alone at 0.5 μ/kg per min did not significantly alter the pressure-natriuresis response in rats with either denervated or innervated kidney. In addition, urinary excretion of dopamine derived from neither neural nor extraneural origins was altered in parallel with variations in mean arterial pressure.ConclusionThese results suggest that exogenous administration of dopamine may affect the pressure-natriuresis response by altering the magnitude of arterial pressure-induced changes in tubular sodium reabsorption, via an action of dopamine-1 receptors. However, endogenous dopamine does not appear to be capable of modulating the pressure-natriuresis response.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo investigate the pathological role of platelet neuropeptide Y (NPY) in genetically hypertensive rats, we measured the platelet content and plasma concentration of immunoreactive (ir)-NPY in hypertensive and normotensive rats and examined the aggregating ability of rat platelets and the NPY releasing reaction in each of these rat types. In addition, we purified platelet NPY and determined its amino acid sequence.Design and methodsTo characterize immunoreactive NPY in rat platelets, rat platelet NPY was purified to homogeneity and the purified peptide was analysed by gas-phase sequencer. Platelet content and plasma concentration of NPY was measured by a sensitive radioimmunoassay for NPY. Aggregating ability was examined by a turbidimetric method; aggregation was recorded for 5 min and the maximum aggregation was read.ResultsRat platelet NPY was purified and the amino acid sequence was determined to be YPSKPDNPGEDAPAEDMARYYSALRHYINUTRQRY. The platelet content of ir-NPY in 5-, 10-, and 15-week-old spontaneously hypertensive rats (SHR) was higher than that in Wistar-Kyoto (WKY) rats of the same age. The platelet content of ir-NPY in 10-week-old stroke prone-SHR was also higher than that in 10-week-old WKY rats. No differences were observed between any of the pairs in any WKY rats, SHR or stroke-prone SHR group with regard to the plasma concentration of ir-NPY. Ir-NPY was not released from rat platelets when adenosine diphosphate was used for aggregation. However, NPY was released from the platelets when they were aggregated by collagen and, furthermore, in this case the amount of NPY released from platelets was greater in SHR than in WKY rats.ConclusionThat the platelet content of NPY in SHR (and stroke-prone SHR) was higher than that in WKY rats seems to be an important genetic characteristic of SHR. As NPY is a potent vasoconstrictor, it may be involved in the progression of vascular lesions.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID