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

The Y chromosome in spontaneously hypertensive rats (SHR) and stroke-prone rats has been shown to contain a locus that contributes to the hypertensive effect; both the sympathetic nervous system and testosterone may be involved. The objective of this study was to look at the effects of testosterone on renal norepinephrine (NE) release and content in the isolated perfused kidney in different Y chromosome backgrounds. The study involved male SHR, Wistar-Kyoto rats (WKY), and 2 consomic strains with different Y chromosomes (n=5 to 8 per group). Adult animals were castrated, and implants containing testosterone propionate were placed at the base of the neck. Blood testosterone levels were measured by radioimmunoassay 2 weeks after castration. The left kidney was isolated and perfused with oxygenated Krebs solution at a constant flow and temperature with KCl and electrical stimulation of the renal nerves. Perfusate was collected and analyzed for NE by high-performance liquid chromatography. Lactate dehydrogenase analyses were performed as a marker for potential tissue damage. Renal perfusate and renal tissue NE levels were significantly elevated by testosterone. The average NE increase with a single testosterone implant was 13.2 ng/mL, and for a double testosterone implant it was 29.8 ng/mL. The Y chromosome from the SHR produced a significant increase in renal NE release compared with the WKY Y chromosome. Significance was shown between all groups: 1 versus 2 implants, P=0.0067; 1 versus sham implants, P=0.015; 2 versus sham implants, P<0.001. In conclusion, testosterone caused an enhanced renal NE release that was strain-specific, with the Y chromosome raising renal NE content and release.
Hypertension 1998 Nov
PMID:Testosterone effects on renal norepinephrine content and release in rats with different Y chromosomes. 982 48

Genetic variation in the Y chromosome has significant effects on male blood pressure in experimental animals, but the effects in humans are unknown. We examined the relationship between blood pressure and a polymorphic HINdIII restriction site in the nonrecombining region of the Y chromosome in 409 randomly selected men from the general population. Carefully standardized measures of systolic and diastolic blood pressures were made. The HINdIII restriction site was significantly more common (43.2%) in men in the lowest decile of the diastolic blood pressure distribution than men in the highest decile (15.9%, P=0.007). No significant difference in genotype frequency was observed between the lowest and highest deciles for systolic pressure (32.4% versus 27.8%, P=0.66). In the entire group, men with the HIN:dIII restriction site had significantly lower diastolic blood pressures (81.2 mm Hg, SD:8.3, versus 83.2 mm Hg, SD:8.7, P=0.03). No significant differences in systolic blood pressure (130.6 mm Hg, SD:14.7, versus 128.3 mm Hg, SD:13.6) were observed in relation to genotypes. Our results indicate that genetic variation in the human Y chromosome is associated with high blood pressure and contributes significantly to the quantitative variation of male diastolic blood pressure in the general population.
Hypertension 2000 Nov
PMID:Association of the human Y chromosome with high blood pressure in the general population. 1108 35

We have previously demonstrated that the SHRSP Y chromosome contains a locus that contributes to hypertension in SHRSP/WKY F2 hybrids and that SHRSP exhibit an increased vulnerability to focal cerebral ischemia after permanent middle cerebral artery occlusion (MCAO). This increased vulnerability is inherited as a codominant trait, and a putative role for the Y chromosome has been suggested in F1 hybrids. The objective of this study was to investigate further the role of Y chromosome in blood pressure (BP) regulation and in the vulnerability to cerebral ischemia. We have constructed consomic strains by selectively replacing the Y chromosome from WKY rats with that of SHRSP, and vice versa, by using a marker-assisted breeding strategy. Permanent MCAO was carried out by electrocoagulation, with infarct volume expressed as a percentage of the ipsilateral hemisphere. Systolic blood pressure was measured by radiotelemetry during a baseline period of 5 weeks followed by a 3-week period of salt loading. We observed that the transfer of the Y chromosome from WKY onto SHRSP background significantly reduced systolic BP in consomic strains, SP.WKYGlaY(w) (n=6) versus SHRSP (n=6) (209.2+/-10.4 mm Hg versus 241.7+/-7.7 mm Hg, F=5.88, P=0.038) during the salt-loading period. In the reciprocal consomic strain, WKY.SPGlaY(s) (n=5), systolic BP was increased compared with WKY parental strain (n=6) (147.6+/-2.4 mm Hg versus 132.6+/-5.1 mm Hg, F=6.11, P=0.035) during baseline. Infarct volumes in consomic strains were not significantly different from their respective parental strain: WKY.SPGlaY(s) (n=7) versus WKY (n=7), 22.8+/-3.7% versus 22.2+/-8.0%, 95% CI=-12.7, 4.2, P=0.3; SP.WKYGlaY(w) (n=7) versus SHRSP (n=6), 37.7+/-4.4% versus 33.6+/-7.6%, 95% CI=-20.3, 12.1, P=0.5. We conclude that the SHRSP Y chromosome harbors a locus contributing to systolic BP, whereas no contribution to vulnerability to cerebral ischemia can be detected.
Hypertension 2001 Feb
PMID:Reciprocal consomic strains to evaluate y chromosome effects. 1123 Mar 6

Previous studies with chromosome-Y consomic strains of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats suggest that a quantitative trait locus for blood pressure regulation exists on chromosome Y. To test this hypothesis in the SHR-Brown Norway (BN) model and to study the effects of chromosome Y on lipid and carbohydrate metabolism, we produced a new consomic strain of SHR carrying the Y chromosome transferred from the BN rat. We found that replacing the SHR Y chromosome with the BN Y chromosome resulted in significant decreases in systolic and diastolic blood pressures in the SHR.BN-Y consomic strain (P<0.05). To elicit possible dietary-induced variation in lipid and glucose metabolism between the SHR progenitor and chromosome-Y consomic strains, we fed rats a high-fructose diet for 15 days in addition to the normal diet. On the high-fructose diet, the SHR.BN-Y consomic rats exhibited significantly increased levels of serum triglycerides and decreased levels of serum HDL cholesterol versus the SHR progenitor rats. Glucose tolerance and insulin/glucose ratios, however, were similar in both strains on both normal and high-fructose diets. These findings provide direct evidence that a gene or genes on chromosome Y contribute to the pathogenesis of spontaneous hypertension in the SHR-BN model. These results also indicate that transfer of the Y chromosome from the BN rat onto the SHR background exacerbates dietary-induced dyslipidemia in SHR. Thus, genetic variation in genes on the Y chromosome may contribute to variation in blood pressure and lipid levels and may influence the risk for cardiovascular disease.
Hypertension 2001 Apr
PMID:Y-chromosome transfer induces changes in blood pressure and blood lipids in SHR. 1130 17

The objective of this study was to compare strain and gender differences in kidney and heart norepinephrine (NE) content and turnover rate in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR, SHR/a, and SHR/y). Our laboratory has shown that the Y chromosome has a significant effect on blood pressure in the SHR model of hypertension through the use of two new rat stains, SHR/a and SHR/y, to study the Y chromosome. SHR/a have a SHR autosomal genetic background with a WKY Y chromosome, whereas the SHR/y rats have a WKY autosomal genetic background with a SHR Y chromosome. Tissues were homogenized after alpha-methyl-DL-p-tyrosine injection and analyzed for NE. The male kidney NE content was significantly lower in the WKY compared with the SHR, SHR/y, and SHR/a. Kidney and heart NE content was significantly higher in females compared with males in all strains except the SHR/y. The WKY and SHR/y females had significantly lower kidney NE turnover rates, and the SHR and SHR/a females had significantly higher kidney NE turnover rates than strain-matched males. This study suggests both a strain and gender difference in sympathetic nervous system activity through noradrenergic neurotransmission.
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PMID:Noradrenergic content and turnover rate in kidney and heart shows gender and strain differences. 1179 65

Higher blood pressure (BP) in males compared with females is well documented and is thought to be influenced in part by the Y chromosome. To examine whether there is an association between BP and a polymorphic HindIII biallelic marker in the nonrecombining region of the Y chromosome, we genotyped 155 males from a Polish study group and 762 males from a Scottish study group. We also tested for possible interaction between the Y chromosome and a mutation in the steroidogenic factor binding site of the aldosterone synthase gene by genotyping the same group from Scotland. There was no significant difference in age or body mass index between 2 Y chromosome genotypes in both study groups. Men with the HindIII(+) genotype had significantly higher systolic and diastolic pressures than those with the HindIII(-) genotype in both the Polish and Scottish studies. This difference between the genotypes was 5.27 mm Hg (P=0.0014) and 3.14 mm Hg (P=0.0005) for adjusted systolic BP and 2.6 mm Hg (P=0.0045) and 1.44 mm Hg (P=0.0084) for adjusted diastolic BP in the Polish and the Scottish studied, respectively. On binary logistic regression analysis, males with the HindIII(+)/TT SF1 genotype combination had an odds ratio for elevated BP of 3.92 (CI 1.21 to 12.68, P=0.023). Our results indicate that the Y chromosome harbors a locus or loci that contribute to BP variation in hypertensive and normotensive men. The polymorphism in the aldosterone synthase gene may interact with the Y chromosome to increase the odds of an individual's developing higher BP.
Hypertension 2002 Feb
PMID:The Y chromosome effect on blood pressure in two European populations. 1188 72

There is an inherited paternal predisposition to hypertension. Y chromosome alphoid satellite variation was recently reported to be linked to diastolic blood pressure. To determine whether there is also a Y chromosome marker linked to hypertension, we investigated the prevalence of the Y chromosome Alu insertion polymorphism (YAP) at DYS287 and its association with hypertension in the Aomori population in the northern area of Honshu Island, Japan. YAP was present in 98 of 285 male residents and absent in the rest. The YAP prevalence in the present study would appear to suggest that the present study population represents the general male population in central Japan. Within the study population, there were 110 hypertensive subjects and 104 normotensive subjects. YAP frequency in the hypertensive subjects was not different from that in the normotensive subjects. These results suggest that the YAP is not likely to be a genetic-susceptibility factor for hypertension in the Aomori population.
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PMID:Lack of association between Y chromosome Alu insertion polymorphism and hypertension. 1192 14

We previously detected by linkage analysis in segregating populations derived from crosses between the Sabra hypertension-prone rat (SBH/y) and the hypertension-resistant strain (SBN/y) two QTLs for salt susceptibility on chromosome 1, with sex specificity: in males SS1a and SS1b, and in females SS1b only. To provide support for a functional role of these QTLs in relation to hypertension, we constructed congenic strains by replacing most of or selected segments from chromosome 1 from SBN/y with the homologous chromosomal regions of SBH/y, or reciprocally from SBH/y with segments of SBN/y, leaving the other chromosomes unperturbed. Genetic screening with over 150 microsatellite markers confirmed the homozygosity of the targeted genomic inserts and of the remainder of the genomic background. The phenotype of the congenic strains was tested by salt loading with DOCA-salt over a 4-wk period and measuring blood pressure by tail-cuff (in all animals) or radiotelemetry (in select groups) at baseline and during salt loading. In the congenic strains in which a chromosomal segment incorporating QTL SS1a from SBN/y was introgressed onto the genomic background of SBH/y, the blood pressure response to salt loading, as measured by tail-cuff, was decreased by 16 mmHg in both males and females compared with the parental SBH/y; replacing the QTL SS1b reduced the blood pressure response by 30 and 21 mmHg, respectively. In the congenic strains in which both SS1a and SS1b were introgressed from SBN/y onto the genomic background of SBH/y, the reduction in blood pressure was 34 mmHg in males and 38 mmHg in females; these latter results were confirmed by radiotelemetry. When either one or both QTLs together were introgressed from SBH/y onto the SBN/y genomic background, tail-cuff measurements failed to detect an increase in blood pressure above baseline; telemetric measurements in the congenic strains introgressing both QTLs together, however, detected a significant rise in blood pressure after 3 and 4 wk of salt loading. Neither the origin of the Y chromosome nor the sex of the parental strain had any significant impact on the magnitude of the blood pressure response to salt loading. We conclude that the congenic rat strains that we constructed for the chromosome 1 QTLs provide functional evidence for the role of gene systems within QTLs SS1a and SS1b in the blood pressure response to salt loading. The unexpected finding was that QTL SS1a contributes to the hypertensive response also in females. The data indicate the lack of a Y chromosomal effect or of parental imprinting.
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PMID:Congenic strains confirm the presence of salt-sensitivity QTLs on chromosome 1 in the Sabra rat model of hypertension. 1244 4

Being male or female can make a vital difference to many important biological functions and can lead to disparities in health. The Y chromosome carries the sex-determining sex reversal Y (SRY) gene and recent studies show that it might also harbor genes that have important biological functions other than sex determination. One such example is the emerging evidence from animal models and humans that supports the presence of cardiovascular genes on the Y chromosome. A significant amount of work remains to identify these genes; however, we report here observations linking the Y chromosome to hypertension, which could explain the higher incidence of cardiovascular disease in males compared with females.
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PMID:Y is there a risk to being male? 1271 76

Although important advances have been made over past decades in studying the mechanisms of hypertension, the nature of cellular signaling patterns involved and their relationship remain unclear. High cGMP production rates in isolated renal glomeruli have been presented as a characteristic of spontaneously hypertensive rat (SHR) even before the development of hypertension, which suggests that this event might be a cause of the increase in blood pressure. Using cross-breeding between SHR and WKY parental strains to obtain F1 and F2 hybrids, we have investigated the patterning of high blood pressure and cGMP production rates. We have found that, in the F2 population, the mean blood pressure and both basal and ANP(1-28)-stimulated cGMP production are similar to the parental SHR. In addition, we have found a positive correlation between blood pressure and high cGMP production rates in the F2 population. The higher cGMP production was not a consequence of hypertension, since in DOCA-salt hypertensive rats cGMP production was similar to that observed in normotensive WKY rats. These observations suggest that high cGMP production is a characteristic linked to hypertension. Finally, reciprocal crosses between the SHR and WKY parental strains showed that in the F1 population blood pressure but not cGMP production are associated with the Y chromosome.
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PMID:Patterning of renal cGMP production by the natriuretic peptide receptor type A and blood pressure in spontaneously hypertensive rats. 1509 96


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