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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasoactive hormones acting as endocrine, neuroendocrine, or local hormonal systems (intracrine, autocrine, and paracrine) are an important component of the many factors that regulate blood pressure. Hypertension may be the result of an alteration in the balance between vasodepressor and vasopressor hormonal systems. Changes in this balance could be due to genetic factors such as mutations in one of the genes of the vasoactive system or environmental factors that alter the synthesis and release of one or more vasoactive hormones. Endocrine and neuroendocrine vasopressor hormonal systems, such as the renin-angiotensin system and catecholamines, play a well-established and important role in the regulation of blood pressure and the pathogenesis of some secondary forms of hypertension. The blockade of such systems has already resulted in effective antihypertensive treatment. The role of local hormonal systems is less well established; however, recent evidence suggests they also play an important role in the regulation of blood pressure and the pathogenesis of hypertension. Some vasopressor hormonal systems, such as the renin-angiotensin system, can act as both endocrine or local hormonal systems. Work using transgenic rats harboring the mouse Ren-2 gene has conclusively demonstrated that the renin-angiotensin system, acting as a local hormonal system, has the capability to cause severe hypertension. Whether this model of experimental hypertension mimics any type of human hypertension is not known. Vasodepressor hormones such as kinins, prostaglandins, and endothelium-derived relaxing factor (EDRF) act mainly as local hormonal systems, with the notable exception of atrial natriuretic factor, which may act as both an endocrine and a local hormone. The tissue kallikrein-kinin system, acting either directly or via paracrine eicosanoids or EDRF, participates in local regulation of the circulation, renal function, and the acute antihypertensive effect of angiotensin converting enzyme inhibitors. A restriction fragment length polymorphism (RFLP) that distinguishes the kallikrein gene family of a strain of spontaneously hypertensive rats (SHR) from normotensive Brown Norway rats has been identified. In a set of 32 recombinant inbred strains derived from these SHR and Brown Norway strains, the RFLP marking the kallikrein gene family of SHR cosegregated with an increase in blood pressure. Also, in a study of Utah families it was found that a dominant-allele kallikrein gene expressed as high urinary kallikrein excretion was associated with a decreased risk of essential hypertension. In conclusion, vasopressor and vasodepressor hormones, acting not only as endocrine but also as local hormones, play an important role in the regulation of blood pressure and the pathogenesis of hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Local hormonal factors (intracrine, autocrine, and paracrine) in hypertension. 188 59

The subject of the work is to assess the clinical parameters and diastolic function in patients with mild or moderate essential hypertension after 5-month treatment with guanfacine 0.5-3 mg/day, mean 1.7 mg. In the group there were 8 women and 8 men, mean age 53.7 +/- 7.6. The diastolic function of the left ventricle was assessed from the echocardiographic M-mode paper sweep of the left ventricle by the method of Gibson and Brown. In clinical parameters systolic, diastolic and mean blood pressure was found to decrease significantly, the heart rate was unchanged. Essential improvement of the markers of relaxation was received while amelioration of filling was not significant. The before treatment data were compared with the similar ones of the 60 persons of the control group. The significant differences were found in values of blood pressure, markers of relaxation and indices Iv and Ip.
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PMID:[Indices of left heart ventricle relaxation after 5-months of hypotensive therapy with guanfacine]. 836 74

Renal kallikrein is one of the tissue kallikreins, and the distal nephron is fully equipped as an element of the kallikrein-kinin system. Although a low excretion of urinary kallikrein has been reported in essential hypertension, the results from studies on patients with hypertension are not consistent. Congenitally hypertensive animals also excrete lowered levels of urinary kallikrein, but the effects of this are yet unknown. Extensive genetic and environmental studies on large Utah pedigrees suggest that the causes of hypertension are closely related to the combination of low kallikrein excretion and the potassium intake. Mutant kininogen-deficient Brown Norway-Katholiek rats, which cannot generate kinin in the urine, are very sensitive to salt loading and to sodium retention by aldosterone released by a non-pressor dose of angiotensin II, which results in hypertension. The major function of renal kallikrein-kinin system is to excrete sodium and water when excess sodium is present in the body. Failure of this function causes accumulation of sodium in the cerebrospinal fluid and erythrocytes, and probably in the vascular smooth muscle, which become sensitive to vasoconstrictors. We hypothesize that impaired function of the renal kallikrein-kinin system may play a pivotal role in the early development of hypertension. Inhibitors of kinin degradation in renal tubules and agents, which accelerate the secretion of urinary kallikrein from the connecting tubules and increase the generation of urinary kinin, may be novel drugs against hypertension.
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PMID:Pivotal role of renal kallikrein-kinin system in the development of hypertension and approaches to new drugs based on this relationship. 886 49

The spontaneously hypertensive rat (SHR) is the most widely studied animal model of essential hypertension. Despite > 30 yr of research, the primary genetic lesions responsible for hypertension in the SHR remain undefined. In this report, we describe the construction and hemodynamic characterization of a congenic strain of SHR (SHR-Lx) that carries a defined segment of chromosome 8 from a normotensive strain of Brown-Norway rats (BN-Lx strain). Transfer of this segment of chromosome 8 from the BN-Lx strain onto the SHR background resulted in substantial reductions in systolic and diastolic blood pressure and cardiac mass. Linkage and comparative mapping studies indicate that the transferred chromosome segment contains a number of candidate genes for hypertension, including genes encoding a brain dopamine receptor and a renal epithelial potassium channel. These findings demonstrate that BP regulatory gene(s) exist within the differential chromosome segment trapped in the SHR-Lx congenic strain and that this region of chromosome 8 plays a major role in the hypertension of SHR vs. BN-Lx rats.
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PMID:Genetic isolation of a region of chromosome 8 that exerts major effects on blood pressure and cardiac mass in the spontaneously hypertensive rat. 904 57

The genes that determine the baseline hematocrit level in humans and experimental animals are unknown. The spontaneously hypertensive rat (SHR), the most widely used animal model of human essential hypertension, exhibits an increased hematocrit when compared with the normotensive Brown Norway (BN-Lx) strain (0.54 +/- 0.02 vs. 0.44 +/- 0.02, p < 0.01). Distribution of hematocrit values among recombinant inbred (RI) strains derived from SHR and BN-Lx progenitors was continuous, which suggests a polygenic mode of inheritance. The narrow heritability of the hematocrit was estimated to be 0.32. The Eno2 marker on Chromosome (Chr) 4 showed the strongest association (p < 0.0001) with the observed variability of hematocrit among RI strains. The erythropoietin (Epo) gene, originally reported to be syntenic with Eno2, has been mapped to Chr 12, thus excluding it as a potential candidate gene for the increased hematocrit in the SHR. The current linkage data extend homologies between rat, mouse, and human chromosomes.
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PMID:Mapping genes controlling hematocrit in the spontaneously hypertensive rat. 916 79

It has been proposed that one of the primary events in the development of essential hypertension is a growth-related process initiated as early as during fetal development. Differences in kidney size have been observed between most rat models of hypertension and their respective controls. In this study, we analyzed relative kidney size (kidney weight/body wt) in a set of rat recombinant inbred strains (RIS) (N = 27) and their progenitors, the spontaneously hypertensive rat strain (SHR/Ola) and Brown Norway congenic strain (BN.1x), at two different ages, at birth and at 15 weeks. In the progenitors, the relative kidney weight was higher in the hypertensive than in the normotensive strain of both the newborn (P < 0.001) and adult (P < 0.001) animals. In the RIS, a significant correlation was found between the newborn and adult relative kidney weight (r = 0.49, P = 0.01), indicating that the two phenotypes share some of their genetic determinants. A total genome search of newborn and adult relative kidney weight was performed with a total of 453 genetic markers. These analyses revealed several suggestive quantitative trait loci (QTL), some of which were, indeed, significant for both newborn and adult relative kidney weight (such as, D3Mit9 on rat chromosome 3; r = -0.50, P < 0.01; r = -0.47, P < 0.01; respectively). Others, such as the locus on rat chromosome 1 (Rt6; r = -0.43, P < 0.05), were significant only for the adult relative kidney size. This QTL was found in close proximity to a region previously related to susceptibility to hypertensive renal disease in the fawn-hooded rat and, similarly to that study, its effect was found to be independent of blood pressure. Furthermore, a growth pattern of the kidneys after birth, evaluated as the difference between the newborn and adult relative kidney weight, was also subjected to total genome scan. Several suggestive QTL were identified. One of the most significant loci was found at the D1a marker on rat chromosome 17 (r = -0.51, P < 0.01), which was previously related to the determination of adult heart weight in the RIS. In conclusion, the current study demonstrates the usefulness of RIS in studies of hypertension-related phenotypes, some of which are abnormal before the development of high blood pressure. To better understand their role in the pathogenesis of hypertension, studies at different ages are needed, which are uniquely feasible in RIS.
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PMID:Newborn and adult recombinant inbred strains: a tool to search for genetic determinants of target organ damage in hypertension. 960 80

Hypertensive disorders complicate approximately 10% of all pregnancies, about half due to transient and essential hypertension and the rest due to preeclampsia that continues to be a major contributor to maternal and perinatal mortality. However, when hypertensive pregnancies are carefully monitored, the neonatal mortality is low. Therefore, identification of women destined to have preeclampsia is essential, and it is the major purpose of the new classification proposed by M. A. Brown and M. L. Buddle to better stratify those hypertensive pregnant women who are at high risk and need intensive inpatient management. Prophylactic low-dose aspirin appeared to prevent preeclampsia in some studies and to be reasonably safe; however, the effectiveness in reducing the incidence of severe preeclampsia and improving pregnancy outcome remains uncertain. The basic therapy for hypertension during pregnancy is now hydralazine, labetalol and methyldopa; for preeclampsia the cornerstone for treatment is magnesium sulphate and hydralazine intravenously, and small doses of diazoxide, if necessary. Diuretics have a dubious place in treatment of hypertension during pregnancy, and ACE-inhibitors are contraindicated. In severe preeclampsia and eclampsia, the only solution is delivery; better knowledge of etiology and pathogenetics is needed for effective and safe treatment of gestational hypertension, as well as careful blood pressure monitoring and adequate laboratory control.
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PMID:[Hypertension and its treatment in pregnancy]. 974 46

Tissue kallikrein and low molecular weight kininogen are localized in the particular cells of the connecting tubules, indicating that kinin is immediately generated in the lumina of the lower nephrons. The role of the renal kallikreinkinin system was studied using mutant kininogen-deficient Brown NorwayKatholiek (BN-Ka) rats, and compared with that in normal BN-Kitasato rats of the same strain. Mutant BN-Ka rats showed no visible changes, but they were very sensitive to excess sodium ingestion and to the tendency of sodium to accumulate in the body by aldosterone released by angiotensin II, so that sodium was accumulated in erythrocytes and cerebrospinal fluid in BN-Ka rats and hypertension was induced. After four days infusion of 0.3 M NaCl solution to conscious and unrestrained mutant BN-Ka rats, the sensitivity of the vascular smooth muscle to norepinephrine and angiotensin II increased 30-fold and 10-fold, respectively. Bradykinin was degraded by neutral endopeptidase (NEP) and carboxypeptidase Y-like exopeptidase (CPY) in rat and human urine. Daily oral administration of a selective inhibitor of CPY, ebelactone B, or that of NEP, BP1O2, prevented development of deoxycorticosterone acetate-salt hypertension in Sprague-Dawley rats. These results indicate that: 1) the renal kallikrein-kinin system allows excretion of excess sodium in the body, 2) decreased sodium excretion due to reduced excretion of urinary kallikrein in patients with essential hypertension or in genetically hypertensive rats may cause hypertension, and 3) urine kininase inhibitors such as ebelactone B may emerge as a new antihypertensive drug.
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PMID:Crucial suppressive role of renal kallikrein-kinin system in development of salt-sensitive hypertension. 983 May 1

Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR. BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypertension in the SHR model. Thus, the ability of chromosome 4 to influence multiple cardiovascular risk factors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR. BN-Il6/Npy strain.
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PMID:Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension. 1037 71

Abnormalities in carbohydrate and lipid metabolism are common in patients with essential hypertension and in the spontaneously hypertensive rat (SHR). To identify chromosome regions contributing to this clustering of cardiovascular risk factors in the SHR, we searched for quantitative trait loci (QTL) associated with insulin resistance, glucose intolerance, and dyslipidemia by using the HXB/BXH recombinant inbred (RI) strains. Analysis of variance in RI strains suggested significant effects of genetic factors. A genome screening of the RI strains with more than 700 markers revealed QTL significantly associated with insulin resistance on Chromosomes (Chrs) 3 and 19. The Chr 19 QTL was confirmed by testing a previously derived SHR-19 congenic strain: transfer of a Chr 19 segment delineated by markers D19Rat57 and D19Mit7 from the Brown Norway (BN/Cr) strain onto the genetic background of the SHR/Ola was associated with decreased insulin and glucose concentrations and ameliorated insulin resistance at the tissue level. These findings suggest that closely linked genes on Chr 19, or perhaps even a single gene with pleiotropic effects, influence the clustering of metabolic disturbances in the SHR-BN model.
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PMID:Genetic analysis of metabolic defects in the spontaneously hypertensive rat. 1201 13


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