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

Platelet cytosolic free calcium concentration ([Ca2+]i) and pH (pHi) have been reported to be altered in both human essential and rat spontaneous hypertension. The aim of our study was not only to search for the occurrence of such alterations in platelets of rats with salt-induced hypertension but also to investigate whether these changes might precede blood pressure rise in this form of experimental hypertension. Using fluorescent probes fura-2 and BCECF, basal values and thrombin-induced changes of [Ca2+]i and pHi were determined in platelets of young hypertension-prone (SBH) and hypertension-resistant (SBN) Sabra rats fed either low-salt (0.3% NaCl) or high-salt (4% NaCl) diets. Under the conditions of low salt intake, basal [Ca2+]i values were similar in SBH and SBN rats, whereas pHi was significantly lower in SBH than in SBN animals. Thrombin induced smaller [Ca2+]i elevation but greater pHi rise in SBH rats compared with SBN animals. The initial rate of thrombin-induced Mn2+ entry, which reflects the opening of a particular subclass of thrombin-operated Ca2+ channels, was similar in both strains. The moderate hypertension elicited in SBH rats by high salt intake was not associated with major alterations of basal [Ca2+]i or pHi values. High salt diet feeding did not influence [Ca2+]i and pHi responses to thrombin in either strain. In contrast, high salt intake reduced thrombin-induced Mn2+ entry in SBN but not in SBH rats. Basal platelet [Ca2+]i values correlated positively with systolic but not with diastolic blood pressure. This could be ascribed to a very close relationship of basal [Ca2+]i values with pulse pressure. The abnormalities of [Ca2+]i and pHi handling in platelets of Sabra rats with salt-dependent genetic hypertension differ from those described in essential hypertensive patients or rat strains with spontaneous forms of genetic hypertension. Our study also indicated that alterations of platelet [Ca2+]i do not precede blood pressure elevation in salt hypertension.
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PMID:Abnormal regulation of cytosolic calcium and pH in platelets of Sabra rats in early phases of salt hypertension development. 902 81

Salt-resistant (SBN/y) and salt-sensitive (SBH/y) Sabra rats are a useful model of salt-sensitive hypertension with incompletely explored renal mechanisms. We investigated their pressure-natriuresis curves, with and without deoxycorticosterone acetate (DOCA)-salt treatment. To differentiate between extrinsic neural and hormonal mechanisms and intrinsic renal influences, we performed experiments with neural denervation, adrenalectomy, and infusions of vasopressin, norepinephrine, 17-hydroxycorticosterone, and aldosterone as well as without these maneuvers. In untreated SBN/y without controlled neural and circulating hormonal factors, urine flow and sodium excretion increased from 32 to 95 microL/min per gram kidney weight (gkwt) and from 4 to 17 mumol/min per gkwt, respectively, as renal perfusion pressure was increased from 85 to 146 mm Hg. Renal blood flow and glomerular filtration rate were autoregulated and averaged 7.5 and 1.2 mL/min per gkwt. In untreated SBN/y with controlled neural and circulating factors, pressure-diuresis and -natriuresis curves were shifted toward the right, and renal blood flow and glomerular filtration rate ranged between 4.2 and 9.1 or 1 and 1.3 mL/min per gkwt as perfusion pressure was increased from 99 to 164 mm Hg. In both protocols, values in SBH/y did not differ. DOCA-salt increased blood pressure in SBH/y. In SBH/y without controlled neural and hormonal factors, pressure-diuresis and -natriuresis curves were shifted approximately 20 mm Hg toward the right. Fractional sodium and water excretion curves, renal blood flow, and glomerular filtration rate were shifted rightward in parallel. On the other hand, SBH/y with DOCA-salt and controlled neural and hormonal factors had lower sodium and water excretion rates only at the renal perfusion pressure of 150 mm Hg as well as decreased renal blood flow and glomerular filtration rate compared with DOCA-salt SBN/y. These data suggest that both extrinsic and intrinsic factors are responsible for reduced sodium and water excretory capacity in DOCA-salt SBH/y; however, the extrinsic factors may be more important.
Hypertension 1997 Jun
PMID:Pressure natriuresis in salt-sensitive and salt-resistant Sabra rats. 918 Jun 25

The molecular mechanisms of salt sensitivity and the contribution of the kidney to salt-induced hypertension in Sabra rats are imperfectly defined. We investigated the expression of the nitric oxide (NO) system (endothelial, inducible, and neural NO synthases) and renin-angiotensin system (renin, angiotensinogen, and angiotensin II type 1A receptor) gene components in the kidneys of SBN/y (salt-resistant) and SBH/y (salt-sensitive) Sabra rat substrains, with and without deoxycorticosterone acetate (DOCA)-salt treatment. We also looked for immunocytochemical evidence of angiotensin II, the effector peptide of the renin-angiotensin system. Inducible and neural NO synthase gene expression values were lower in SBH/y than in SBN/y before and after DOCA-salt treatment. The gene expression level of endothelial NO synthase was not different in SBH/y and SBN/y, either with or without DOCA salt. Renin gene expression was significantly higher in kidneys of SBN/y than in kidneys of SBH/y rats, whereas angiotensinogen gene expression was significantly lower in SBN/y. After DOCA-salt treatment, renin gene expression was strongly suppressed in both strains but more so in SBH/y. Angiotensinogen gene expression, on the other hand, was increased by DOCA salt in SBN/y rats so that the two strains were no longer different. Angiotensin II immunoreactivity was significantly higher in SBN/y than in SBH/y; however, after DOCA salt, immunoreactivity in both strains was no longer detectable. Angiotensin II type 1A receptor gene expression was not different between the two strains, either before or after DOCA-salt administration. We conclude that DOCA salt induced a decrease in the activity of the renin-angiotensin system but did not change NO synthase gene expression in SBH/y and SBN/y. Inducible and neural NO synthase gene expression values were less in SBH/y than in SBN/y, independent of DOCA-salt administration. Thus, the NO system could explain, at least in part, the salt resistance of SBN/y.
Hypertension 1997 Sep
PMID:Nitric oxide synthase and renin-angiotensin system gene expression in salt-sensitive and salt-resistant Sabra rats. 931 25

Cationic colloid gold, a polycationic histochemical probe, was used to analyze the distribution of glomerular basement membrane (GBM) polyanions, including heparan sulfate protoglycan in genetic salt-sensitive (SBH/Y) and resistant (SBN/Y) hypertensive rats, with or without high dietary salt intake. GBM morphology, renal function and nitric oxide, as measured by plasma and urine nitrite (NO2) and nitrate (NO3) were also determined. In the salt-sensitive rats the high-salt dietary intake resulted in severe hypertension, proteinuria and decreased glomerular filtration rate. After 1 month of high-salt intake, the average width of the GBM of salt-sensitive rats was higher by 27% than that of salt-resistant rats. The number of GBM anionic sites (lamina rata externa and interna) was much lower in both salt-sensitive and salt-resistant groups after 1 month of salt loading, 8.04+/-0.36 and 7.8+/-0.25 counts/cm, respectively, compared to the respective values of non-salt-loaded animals, 20.58+/-1.08 counts/cm in the SBH/Y (p < 0.001) and 21+/-1.86 counts/cm in the SBN/Y (p < 0.001). A decreased nitric oxide production was found in the salt-sensitive rats before and after salt loading compared with the salt-resistant group. No correlation was found between the nitric oxide changes and the GBM modifications. It is concluded that high-salt intake may be deleterious to the permselectivity of the GBM. It is suggested that salt restriction in hypertension may have a beneficial effect in preventing GBM permselectivity changes and proteinuria.
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PMID:Glomerular basement membrane polyanionic sites and nitric oxide in genetically salt-sensitive and resistant hypertensive rats. 939 26

Random genome screening was initiated in the Sabra rat model of hypertension in search of genes that account for salt sensitivity or salt resistance in terms of the development of hypertension. Female salt-sensitive Sabra hypertension-prone (SBH/y) rats were crossed with male salt-resistant Sabra hypertension-resistant (SBN/y) rats, resulting in an F2 cohort consisting of 100 males and 132 females. Systolic blood pressure (BP) was measured in rats at 6 weeks of age under basal conditions and after 4 weeks of salt loading. Genotypes for 24 polymorphic microsatellite markers localized to chromosome 1 and for 8 markers localized to chromosome 17 were determined in F2 and cosegregation with BP was evaluated by ANOVA and multipoint linkage analysis. Basal BP did not cosegregate with any locus on chromosomes 1 or 17. In contrast, BP after salt loading showed significant cosegregation with three QTLs, two on chromosome 1 and one on chromosome 17, designated SS1a, SS1b, and SS17, respectively; the maximal logarithm of the odds (LOD) scores were 4.71, 4.91, and 3.43, respectively. Further analysis revealed sexual dimorphism. In male F2, BP response to salt loading cosegregated with one QTL (LOD score 4.52) and a second QTL (LOD score 2.98), both on chromosome 1 and coinciding with SS1a and SS1b, respectively. In female rats, BP response cosegregated with one QTL on chromosome 1 (LOD score 3.08) coinciding with SS1b, and with a second QTL on chromosome 17 (LOD score 3.66) coinciding with SS17. In males, the additive effects of the two QTLs on chromosome 1 accounted for most of the BP variance to salt loading, whereas in females the additive effects of the QTLs on chromosomes 1 and 17 accounted for over two thirds of the variance. These results identify three putative gene loci on chromosomes 1 and 17 that contribute importantly to salt sensitivity and/or resistance and uncover sex specificity in the role that salt susceptibility genes fulfill in the development of hypertension.
Hypertension 1998 Jan
PMID:Salt susceptibility maps to chromosomes 1 and 17 with sex specificity in the Sabra rat model of hypertension. 944 2

The Sabra salt-sensitive SBH/y and salt-resistant SBN/y rats constitute a unique experimental model of hypertension in which salt-susceptibility is genetically determined and expressed only after salt-loading, without the development of spontaneous hypertension. To determine the genetic basis of salt-susceptibility in the Sabra rats, the candidate gene and total genome screen approaches were adopted. The likely candidate genes in this model incorporate salt-related physiological mechanisms such as the nitric oxide system, the arginine vasopressin axis and the epithelial sodium channel. In the random genome search scheme for culprit genes, SBH/y and SBN/y were cross-bred. A highly unusual and composite mode of transmission of salt-susceptibility was found in this cross, emphasizing the complexity of the genetic basis of salt-susceptibility. Linkage analysis of the entire rat genome with a large number of widely distributed microsatellite markers identified three putative gene loci on chromosomes 1 and 17 that contribute importantly to salt-sensitivity and/or resistance, and uncovered sex specificity in the role that salt-susceptibility genes fulfill in the development of hypertension.
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PMID:Genetic basis of salt-susceptibility in the Sabra rat model of hypertension. 960 81

Studies in humans have suggested that hyperinsulinemia might play an important role in salt sensitivity and in the later development of high blood pressure. This possibility has been tested in this study on Sabra rats, an animal model of salt-induced hypertension. Salt-sensitive (SBH) and salt-resistant (SBN) Sabra rats have been submitted to either a normal (0.2% NaCl) or a high salt (8% NaCl) diet for 6 weeks. Comparisons of blood pressure, basal glucose and insulin levels, and insulin response to glucose overload (1 g/kg) have been made. As pancreatic alpha2-adrenergic receptors are implicated in the control of insulin release, their densities have been determined on plasma membranes by saturation studies with [3H]-RX-821002 as the specific radioligand. Under normal diet, blood pressures were respectively 133 +/- 9 and 108 +/- 10 mm Hg (n = 6) in SBH and SBN. Basal glucose and insulin levels and insulin response to glucose overload were found to be significantly higher in SBH than in SBN. In contrast, alpha2-adrenergic receptor densities were lower (P < .001) in SBH when compared to SBN. High salt diet increased (P < .01) blood pressure, decreased basal glucose (P < .01) and insulin (P < .001) levels only in SBH. However, when compared to SBN the insulin response to glucose overload was maintained higher in SBH. Alpha2-adrenergic receptor densities and difference between SBH and SBN did not differ from those found in normal diet. In conclusion, the salt-induced high blood pressure of salt-sensitive Sabra rats is not associated with hyperinsulinemia and insulin resistance. Indeed, an improvement in the insulin sensitivity appears to be induced by either a high salt diet or high blood pressure.
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PMID:Insulinemia and pancreatic alpha2-adrenoceptors in salt-sensitive (SBH) and salt-resistant (SBN) Sabra rats: effect of high salt diet. 968 39

We carried out a total genome screen in the Sabra rat model of hypertension to detect salt-susceptibility genes. We previously reported in male animals the presence of 2 major quantitative trait loci (QTLs) on chromosome 1 that together accounted for most of the difference in the blood pressure (BP) response to salt loading between Sabra hypertension-prone rats (SBH/y) and Sabra hypertension-resistant rats (SBN/y). In females, we reported on 2 major QTLs on chromosomes 1 and 17 that together accounted for only two thirds of the difference in the BP response between the strains. On the basis of phenotypic patterns of inheritance in reciprocal F2 crosses, we proposed a role of the X chromosome. We therefore continued the search for the missing QTL in females that would account for the remaining difference in the BP response between the 2 strains using newly developed microsatellite markers and focusing on chromosome X. We screened an F2 cross, consisting of 371 females and 336 males, using 19 polymorphic chromosome X microsatellite markers. We analyzed the averages of BP by genotype using ANOVA and the individual data using MAPMAKER/QTL. In female F2 progeny, we identified a segment on chromosome X that spans over 33.4 cM and shows significant cosegregation (P<0.001) of 14 microsatellite markers (demarcated by DXRat4 and DXMgh10) with systolic BP after salt loading. This segment has 2 apparent peaks at DXRat4 and DXRat13, with a BP effect of 14 mm Hg for each. Multipoint linkage analysis with a free model detected 3 peaks (logarithm of the odds ratio [LOD] score >4.3) within the same chromosomal segment: One between DXMgh9 and DXMit4 (LOD 4.9; 6.1% of variance), a second between DXMgh12 and DXRat8 (LOD 5.2; 7.2% of variance), and a third between DXRat2 and DXRat4 (LOD 5.8; 7.5% of variance). On the basis of these findings and until congenic strains become available, our working assumption is that within chromosome X, 1 to 3 genetic loci contribute importantly to the BP response of female Sabra rats to salt. In male F2 progeny, we detected no significant cosegregation of any region on chromosome X with the BP response to salt loading. We conclude that in the female rat, salt susceptibility is mediated by 3 to 5 gene loci on chromosomes 1, 17, and X, whereas in the male rat, the X chromosome does not affect the BP response to salt.
Hypertension 1999 Jan
PMID:Role of chromosome X in the Sabra rat model of salt-sensitive hypertension. 993 Nov 14

Mechanosensitive ion channels have been suggested to act as endothelial mechanosensors for hemodynamic forces. The present study tested the hypothesis that the pressure-activated cation channel (PAC), a novel type of endothelial mechanosensitive ion channel, is involved in salt sensitivity in the Sabra rat model of hypertension. Groups of Sabra salt-sensitive (SBH/y) and salt-resistant (SBN/y) rats were loaded with deoxycorticosterone-acetate (DOCA)-salt for 8 wk or were fed a regular diet. Single channel function of PAC in SBH/y and SBN/y rats was investigated in intact endothelium of mesenteric artery using the patch-clamp technique. After DOCA-salt treatment, the SBH/y rats showed a full hypertensive response, whereas SBN/y rats were normotensive. Rats of both strains that received a regular diet were normotensive. In endothelium of both Sabra rats, Ca(2+) permeable PAC that was activated by positive pipette pressures was identified. Apparent PAC density (percentage of patches with PAC activity) was reduced in hypertensive SBH/y rats that were loaded with DOCA-salt compared with salt-loaded normotensive SBN/y rats (6 +/- 2% versus 24 +/- 8%, respectively; P < 0.05). In normotensive SBH/y and SBN/y rats that received a regular diet, PAC density was not altered. Mechanosensitivity and unitary conductance of endothelial PAC were similar in both strains under a regular diet as well as salt loading with DOCA-salt. In conclusion, the decreased density of PAC in mesenteric endothelium from hypertensive SBH/y rats indicates an impaired ion channel regulation. The defective PAC function presumably leads to an impaired mechanosensitive Ca(2+) entry and might contribute to endothelial dysfunction and high BP in this type of salt-sensitive genetic hypertension.
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PMID:Impaired function of endothelial pressure-activated cation channel in salt-sensitive genetic hypertension. 1146 34

This study investigates the incidence of high-salt diet in blood pressures, renal alpha(2)-adrenoceptor subtypes distribution, and gene expression in salt-sensitive (SBH) and salt-resistant (SBN) Sabra rats. Comparisons have been made between SBH and SBN rats submitted to a normal or a high-salt diet for 6 weeks. Only alpha(2)B-adrenoceptors are detected in kidneys of SBH rats, whatever the diet. In contrast, mRNA corresponding to alpha(2)A- and alpha(2)B-subtypes are found in this substrain. In these rats, high-salt diet increases blood pressures and up-regulates gene expression and density of only alpha(2)B-adrenoceptors. Inversely, alpha(2)A- and alpha(2)B-adrenoceptors and corresponding mRNA are found in kidneys of SBN rats. In these rats, a high-salt diet does not affect blood pressures but increases gene expression and densities of both alpha(2)A- and alpha(2)B-adrenoceptors. If the up-regulation of renal alpha(2)B-adrenoceptor subtypes is indicative of the hypertensive phenotype, the present study shows that this mechanism is also present in normotensive salt-resistant Sabra rats. In fact, the absence of alpha(2)A-adrenoceptors in SBH could be responsible for the lack of adequate receptor-mediated renal functions predisposing to salt-sensitivity and consequently the development of hypertension. Conversely, the presence of this receptor in SBN rats and its up-regulation could be protective change against the increase of alpha(2)B-adrenoceptors induced by the salt overload and could consequently be responsible for the resistance to salt-induced hypertension.
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PMID:An up-regulation of renal alpha(2)A-adrenoceptors is associated with resistance to salt-induced hypertension in Sabra rats. 1171 78


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