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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nature of all of the peptides critical to the mechanism(s) of the antihypertensive action of neutral endopeptidase (NEP) inhibitors is still unclear, but bradykinin is thought to be one such peptide. This study was designed to assess the effectiveness of an NEP inhibitor in deoxycorticosterone acetate (DOCA)-salt treated kininogen-deficient Brown Norway Katholiek (BN-Ka) rats. Oral administration of BP102 (10-100 mg/kg), an NEP inhibitor, increased urine volume and urinary sodium excretion in a dose-dependent manner in anesthetized Sprague-Dawley rats. DOCA-salt hypertension was induced in both BN-Ka and Brown Norway Kitasato (BN-Ki) rats after left nephrectomy. The development of DOCA-salt hypertension in normal BN-Ki rats was prevented, and that in BN-Ka rats was also significantly reduced, by an 8-day administration of BP102. When BP102 was administered for 5 weeks, the high blood pressure of DOCA-salt treated BN-Ka rats was markedly lowered, and their heart weights were reduced. These results suggest that kinins play no role in the antihypertensive effect of this inhibitor and that other factors may be involved in this effect.
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PMID:Effects of a neutral endopeptidase inhibitor, BP102, on the development of deoxycorticosterone acetate-salt hypertension in kininogen-deficient Brown Norway Katholiek rats. 963 1

To examine arterial mechanical changes during aging, pressure-radius and axial force-radius curves were measured in vivo in carotid arteries from 6- and 23-month-old Brown Norway X Fischer 344 rats. Incremental passive circumferential stiffness (measured at 50, 100, and 200 mm Hg) was higher (P<0.01) in the 23- compared with the 6-month-old rats (14.02+/-1.23 versus 6.58+/-1.51; 2.68+/-0.56 versus 0.99+/-0.34; 1.10+/-0.24 versus 0.69+/-0.15 dyne/mm2x10(3), respectively). Incremental passive axial stiffness was increased (P<0.01) in the 23- compared with the 6-month-old rats (7.95+/-0.70 versus 4.24+/-0.81; 1.91+/-0.10 versus 0.61+/-0.16; 0.58+/-0.09 versus 0.36+/-0.06 dyne/mm2x10(3), respectively). Active incremental circumferential arterial stiffness at 100 and 200 mm Hg was increased (P<0.01) in the older rats. In 6-month-old rats, activation of vascular smooth muscle enhanced (P<0.01) the incremental circumferential and axial stiffness measured at 200 mm Hg. In 23-month-old rats, only active incremental stiffness was increased (P<0.01) at 200 mm Hg. Aging increased (P<0.05) media thickness, collagen content, and the collagen/elastin ratio by 12%, 21%, and 38%, respectively. Elastin density and the number of smooth muscle cell nuclei were decreased by 20% and 31%, respectively, with aging. Thus, structural alterations that occur with aging are associated with changes in both active and passive stiffness. Vascular smooth muscle tone modulates arterial wall anisotropy differently during aging.
Hypertension 1998 Sep
PMID:Large artery remodeling during aging: biaxial passive and active stiffness. 974 Jun 8

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

Linkage studies in the spontaneously hypertensive rat (SHR) have suggested that a gene or genes regulating blood pressure may exist on rat chromosome 19 in the vicinity of the angiotensinogen gene. To test this hypothesis, we measured blood pressure in SHR progenitor and congenic strains that are genetically identical except for a segment of chromosome 19 containing the angiotensinogen gene transferred from the normotensive Brown Norway (BN) strain. Transfer of this segment of chromosome 19 from the BN strain onto the genetic background of the SHR induced significant decreases in systolic and diastolic blood pressures in the recipient SHR chromosome 19 congenic strain. To test for differences in angiotensinogen gene expression between the congenic and progenitor strains, we measured angiotensinogen mRNA levels in a variety of tissues, including aorta, brain, kidney, and liver. We found no differences between the progenitor and congenic strains in the angiotensinogen coding sequence or in angiotensinogen expression that would account for the blood pressure differences between the strains. In addition, no significant differences in plasma levels of angiotensinogen or plasma renin activity were detected between the 2 strains. Thus, transfer of a segment of chromosome 19 containing angiotensinogen from the BN rat into the SHR induces a decrease in blood pressure without inducing any major changes in plasma angiotensinogen levels or plasma renin activity. These results indicate that the differential chromosome segment trapped in the SHR chromosome 19 congenic strain contains a quantitative trait locus that influences blood pressure in the SHR but that this blood pressure effect is not explained by differences in plasma angiotensinogen levels or angiotensinogen expression.
Hypertension 1999 Jan
PMID:Effect of chromosome 19 transfer on blood pressure in the spontaneously hypertensive rat. 993 Nov 13

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

Linkage studies in the fawn-hooded hypertensive rat have suggested that genes influencing susceptibility to hypertension-associated renal failure may exist on rat chromosome 1q. To investigate this possibility in a widely used model of hypertension, the spontaneously hypertensive rat (SHR), we compared susceptibility to hypertension-induced renal damage between an SHR progenitor strain and an SHR congenic strain that is genetically identical except for a defined region of chromosome 1q. Backcross breeding with selection for the markers D1Mit3 and Igf2 on chromosome 1 was used to create the congenic strain (designated SHR.BN-D1Mit3/Igf2) that carries a 22 cM segment of chromosome 1 transferred from the normotensive Brown Norway rat onto the SHR background. Systolic blood pressure (by radiotelemetry) and urine protein excretion were measured in the SHR progenitor and congenic strains before and after the induction of accelerated hypertension by administration of DOCA-salt. At the same level of DOCA-salt hypertension, the SHR.BN-D1Mit3/Igf2 congenic strain showed significantly greater proteinuria and histologically assessed renal vascular and glomerular injury than the SHR progenitor strain. These findings demonstrate that a gene or genes that influence susceptibility to hypertension-induced renal damage have been trapped in the differential chromosome segment of the SHR.BN-D1Mit3/Igf2 congenic strain. This congenic strain represents an important new model for the fine mapping of gene(s) on chromosome 1 that affect susceptibility to hypertension-induced renal injury in the rat.
Hypertension 1999 Aug
PMID:Genetic isolation of a chromosome 1 region affecting susceptibility to hypertension-induced renal damage in the spontaneously hypertensive rat. 1045 39

Recent studies indicate that during early phases of life the kallikrein-kinin system (KKS) plays a role in kidney development. In the rat kidney, the spatial and temporal pattern of expression of the genes encoding for kallikrein or bradykinin (BK) B2-receptors parallels postnatal nephrogenesis and blood flow redistribution from the inner to the outer renal cortex. Animal models with genetic dysfunction of the renal KKS show alterations in the functional maturation of the kidney, and ultimately develop salt-sensitive hypertension. Kininogen-deficient Brown Norway Katholiek rats have undetectable urinary kinin levels and show an exaggerated blood pressure sensitivity to chronic excess of salt or mineralocorticoids. Another rat model with genetic reduction in urinary kallikrein excretion is characterized by an altered pressure-natriuresis relationship, with this defect being corrected by infusion of purified rat tissue kallikrein. Knockout mice lacking the BK B2-receptor gene show elevated blood pressure and heart rate under basal conditions and enhanced blood pressure sensitivity to salt. In rats, prenatal blockade of the BK B2-receptor by icatibant leads to a cardiovascular phenotype similar to that of animals with genetic defects of the KKS. Delayed renal maturation is observed when high salt intake is associated with icatibant. Collectively, these findings indicate a relevant role of the KKS in the physiologic maturation of renal and cardiovascular phenotypes. Genetic or environmental factors, able to potentiate the activity of the renal KKS, could protect against the development of arterial hypertension.
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PMID:Role of the kallikrein-kinin system in the maturation of cardiovascular phenotype. 1056 Jul 85

We have previously reported that the renal kallikrein-kinin system suppressed the development of hypertension, using kininogen deficient Brown Norway Katholiek rats. Kinins were degraded in urine mainly by carboxypeptidase Y-like kininase (CPY). Blockade of renal kinin degradation may prevent the experimental hypertension through the facilitation of the renal kallikrein-kinin system. Daily administration of ebelactone B (EB), which is isolated from Actinomycetes and strongly inhibits CPY, from the first day of deoxycorticosterone acetate (DOCA)-salt treatment for 4 weeks completely blocked hypertension in Sprague-Dawley rats. This treatment reduced sodium levels in erythrocytes and cerebrospinal fluids (CSF) significantly. By contrast, an ACE inhibitor, lisinopril did not prevent hypertension. The development of hypertension in young spontaneously hypertensive rats was also blunted by EB with reductions in sodium levels in erythrocytes and in CSF. The arterial kinin levels in rats undergoing DOCA-salt treatment were 2.2 +/- 0.2 pg/ml, which were increased significantly to 4.6 +/- 0.4 pg/ml with captopril (10 mg/kg, s.c.). The increased kinin levels were less than those to show hypotension. EB did not increase the arterial kinin levels, with significant increase in urinary kinin secretion. These results suggested that facilitation of the renal kallikrein-kinin system by inhibition of kinin degradation on the luminal side of the renal tubules may effectively prevent hypertension.
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PMID:Facilitation of renal kallikrein-kinin system prevents the development of hypertension by inhibition of sodium retention. 1060 38

Linkage studies in segregating populations derived from the spontaneously hypertensive rat (SHR) indicate that a blood pressure quantitative trait locus exists on rat chromosome 1 in the vicinity of the Sa gene. On the basis of these findings and the observation of increased renal expression of the Sa gene in SHR versus normotensive rats, the Sa gene has been proposed as a candidate gene for spontaneous hypertension. In SHR congenic strains, we and others have found that replacement of a segment of SHR chromosome 1 that contains the Sa gene with the corresponding chromosome segment from a normotensive Brown Norway (BN) rat or Wistar-Kyoto rat can reduce blood pressure. To test whether the Sa gene is necessary for the effect of this region of chromosome 1 on blood pressure, we studied a new SHR congenic subline that harbors a smaller segment of BN chromosome 1 that does not include the Sa gene. Transfer of this subregion of chromosome 1 from the BN rat onto the SHR background was associated with significant reductions in blood pressure comparable to those previously observed on transfer of a larger region of chromosome 1 that included the Sa gene. Thus, in the SHR-BN model of hypertension, the results of these mapping studies (1) demonstrate that molecular variation in the Sa gene is not required for the effect of this region of chromosome 1 on blood pressure and (2) should direct attention toward other candidate genes within the differential chromosome segment of the new congenic subline.
Hypertension 2000 Jan
PMID:Genetic analysis of rat chromosome 1 and the Sa gene in spontaneous hypertension. 1064 2


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