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:

Purpose:To review evidence that essential hypertension is a growth-related disorder with origins in childhood and manifestations in adult life.Principal evidence:Blood pressure rises with age in children and adults. In children, the rise closely relates to growth and to skeletal and sexual maturation. Adolescents with highest pressure are heavier and had as children grown fastest; as adults, they show the greatest increase of pressure with age and are more likely to develop hypertension and coronary heart disease. In adults, the rate of increase of pressure relates to earlier pressure. One interpretation of this is that a self-perpetuating mechanism is at work. Genetic and environmental factors influence these events.Hypothetical mechanisms:Most forms of secondary hypertension have two pressor mechanisms; a primary cause, e.g. renal clip, and a second process, which is slow to develop, capable of maintaining hypertension after removal of the primary cause, and probably self-perpetuating in nature. We suggest that essential hypertension also has two mechanisms, both based upon cardiovascular hypertrophy: (1) a growth-promoting process in children (equivalent to the primary cause in secondary hypertension); and (2) a self-perpetuating mechanism in adults.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Background:Primary hypertension is a hereditary disorder characterized by a complex etiological interplay of multiple genetic and environmental factors, until now defying attempts at identifying pathogenetically important genes. The marriage of classical genetics and molecular techniques is now offering a powerful set of tools to uncover such disease-relevant genes.Summary:Based upon the availability of methods to directly examine chromosomal and genomic DNA structures, molecular genetics has at its disposal today an array of markers far more numerous and specific than the phenotype parameters used in classical genetics. In addition, use of DNA polymorphisms takes the process of genetic analysis immediately to that level of investigation — the genome — from which relevant data will ultimately come forth. The deployment of these tools in the pursuit of elucidating the pathogenesis of hereditary hypertension, and their use for two commonly applied strategies, candidate gene analysis and reverse genetics, are discussed.Significance:Whilst still in its early stages, the application of molecular genetic methods to the study of hereditary hypertension now holds the realistic promise of identifying disease-relevant genes. This will provide the basis for advanced diagnostic, preventive and therapeutic approaches.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objectives:The borderline hypertensive rat (BHR) is the first generation offspring of a mating between a female spontaneously hypertensive rat and a male normotensive Wistar-Kyoto rat. With increased dietary NaCI intake, the BHR develops hypertension and augmented cardiovascular and renal responses to acute environmental stress. This investigation sought to examine the role of extracellular fluid volume (ECFV) in these changes.Design:Three groups of 16-week-old BHR were studied: (1) rats on a 1% NaCI diet for 12 weeks; (2) rats on an 8% NaCI diet for 12 weeks; and (3) rats on an 8% NaCI diet for 12 weeks plus furosemide (50mg/kg, i.p., twice daily) for the preceding 2 days.Methods:Rats were chronically instrumented for the measurement of mean arterial pressure (MAP), heart rate and renal hemodynamic, excretory and sympathetic nerve activity responses to acute environmental stress (acute air jet stress). ECFV was measured as inulin space.Results:BHR fed an 8% NaCI diet had increased MAP, urinary sodium excretion and ECFV compared with those fed a 1 % NaCI diet; they also exhibited augmented pressor, tachycardic, renal sympathetic nerve excitatory and antinatriuretic responses to acute environmental stress. When 8% NaCI-diet BHR were treated with furosemide for 2 days, arterial pressure, urinary sodium excretion, ECFV and cardiovascular and renal responses to acute environmental stress returned to values seen in 1% NaCI-diet BHR.Conclusions:The hypertension and increased cardiovascular and renal responses to acute environmental stress produced by increased dietary NaCI intake in BHR derive from a central nervous system site of action via a mechanism(s) related to ECFV and/or sodium.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objective:The purpose of the present investigation was to compare calcium sensitivity of contractile machinery in aorta and portal vein smooth muscle cells (SMC) in normotensive Wistar—Kyoto (WKY) rats and spontaneously hypertensive Okamoto rats (SHR), and to shed light upon the mechanisms of possible differences.Design:Investigations into calcium sensitivity of SMC myofilaments can only be made on skinned muscular strips.Methods:The vascular strips were made hyperpermeable by detergent skinning with saponin. The isometric calcium-induced contractions of SMC were recorded using a force displacement transducer coupled to a physiograph.Results:It was shown that the pCa-tension (negative logarithm of calcium concentration versus tension) relationship for aorta and portal vein SMC in SHR shifted to the left in comparison with WKY rats. Putative protein kinase C inhibitors 1-(S-isoquionolinyl-sulfonyll)-2-methylpiperasine (H-7) and polymyxin B shifted the pCa-tension relationship more significantly to the right in the SMC of SHR than in WKY rats. It has also been shown that H-7 and polymyxin B sharply reduced the maximum tension developed by SMC in SHR whilst causing a non-significant decrease in maximum tension of SMC from WKY rats. These results are consistent with higher protein kinase C activity in SMC of SHR.Conclusion:These results indicate that the increase in calcium sensitivity of vascular SMC contractile machinery in SHR may be linked with the increase in their protein kinase C activity.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objective:To investigate whether the reported association between insulin resistance and hypertension in spontaneously hypertensive rats (SHR) is a primary defect or a secondary phenomenon in hypertension.Design:Comparisons of glucose metabolism between three groups of hypertensive rats: deoxycorticosterone (DOCA)-salt hypertensive rats; two-kidney, one clip renovascular hypertensive (RVH) rats; SHR; and their respective control groups. There was also an additional group of weight-matched SHR and respective Wistar—Kyoto (WKY) controls.Methods:A trace amount of3H-deoxyglucose (3H-DOG) was administered in vivo to evaluate its plasma half-life and tissue uptake. In vitro adipose tissue segments were incubated with14C-glucose and increasing doses of insulin.Results:Compared with age-matched WKY rats, SHR had significantly higher insulin levels, longer plasma half-life and lower3H-DOC uptake by heart and striated muscle. Plasma glucose levels and incorporation of14C-glucose into CO2, triglycerides and glycogen by adipose tissue in response to increasing insulin concentrations was similar for both groups of SHR and WKY rats. No differences were found between hypertensive rats and controls in either the DOCA or RVH groups.Conclusion:Evidence of insulin resistance in spontaneous, but not secondary, rat hypertension indicates that the resistance is a primary rather than a secondary event in hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objectives:Hypertension in humans and experimental animals is known to be associated with an increase in left ventricular myocardial mass. The development of cardiac hypertrophy is not caused by increased blood pressure alone; the autonomic nervous system may also play an important role.Design:The functional responses to the β-adrenoceptor agonists isoprenaline, dobutamine, salbutamol and terbutaline, and the α1-adrenoceptor agonists methoxamine, cirazoline and phenylephrine were studied in isolated (Langendorff) hearts from spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) controls. The results were compared with data from radioligand binding experiments.Results:There was no significant difference in the increase of left ventricular pressure induced by all β-adrenoceptor agonists studied in SHR and WKY rat hearts. Although there was no significant difference in the response to phenylephrine, the inotropic responses to cirazoline and methoxamine proved to be significantly weaker in hearts from SHR than in those from WKY rats. Binding experiments with3H-prazosin revealed no differences in density or affinity for cardiac tissues from SHR and WKY rats.Conclusions:Long-standing hypertension leads to an impaired response of the isolated heart to α1-padrenoceptor stimulation, without changes in α1-receptor density or affinity. It seems likely that changes in postreceptor events are responsible for the impaired inotropic response to α1-adrenoceptor agonists in hearts from SHR.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objective:Abnormalities in the vascular renin—angiotensin system have been hypothesized to contribute to the pathogenesis and complications of hypertension. In animal models of hypertension, there is wide variation in reported vascular angiotensin converting activity, particularly in cerebral microvessels. In this study, we sought to characterize, quantitate and compare cerebral microvessel angiotensin converting enzyme (ACE) in genetically hypertensive rats and normotensive rats.Design:Brain microvascular ACE from 14-week-old spontaneously hypertensive rats (SHR) was measured and compared with ACE from brain microvessels of normotensive Wistar-Kyoto (WKY) controls.Methods:Isolated cerebral microvascular ACE was measured using two methods, enzyme kinetic assay or radioligand binding assay.Results:In SHR, cerebral microvessel ACE was of similar activity and concentration and had similar ligand binding affinities to WKY rats. Plasma ACE activity was significantly elevated in WKY rats compared with SHR.Conclusion:Cerebral microvascular ACE is similar in SHR and WKY rats. Microvascular ACE is unlikely to participate in the pathogenesis or complications of hypertension in this model.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objective:The goal of the present study was to show that, in contrast to an angiotensin converting enzyme (ACE) inhibitor, Ro 42-5892, a new renin inhibitor, can block the renin-angiotensin system without potentiating skin reactions induced by bradykinin.Design:Potentiation of skin reaction to i.d. injections of bradykinin and histamine was evaluated in guinea pigs in the presence and absence of the drug (placebo, Ro 42-5892 or cilazapril). The elimination rate of radioactive bradykinin in blood was measured in other groups of guinea pigs treated with the same drugs. Maximal effective doses of each drug were used.Methods:Measurements of erythema area induced by bradykinin and histamine injection were performed using a digital planimeter. Radioactive bradykinin was measured in blood by high-performance liquid chromatography and followed over 40 min.Results:The ACE inhibitor cilazapril increased the area of erythema induced by bradykinin but not that induced by histamine. In contrast, Ro 42-5892 did not potentiate the effect of bradykinin. In addition, cilazapril did not change the elimination rate of i.v. radioactive bradykinin in blood.Conclusion:These results suggest that potentiation of bradykinin-induced skin reaction by cilazapril is due to a tissular (and not systemic) inhibition of ACE and does not occur with Ro 42-5892. Thus, side effects such as rash, angioneurotic edema or cough, which have been attributed to bradykinin accumulation by ACE inhibitors, may not occur with the use of specific renin inhibitors such as Ro 42-5892.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID