Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Background-Reports demonstrating sympathetic hyperactivity in hypertension with the use of microneurography have been inconsistent. One possible reason is that previous studies have assessed muscle sympathetic nerve activity (MSNA) from integrated voltage waves ("bursts") recorded from multiunit discharges. We studied single units with defined vasoconstrictor properties (s-MSNA) to further characterize sympathetic output in hypertensive disease. Methods and Results-We examined 74 subjects with a wide range of arterial blood pressure that were considered to be either normal (NT), high normal (HN), or stages 1 to 3 essential hypertension (EHT-1, EHT-2/3). All had their peripheral sympathetic activity measured from both multiunit bursts and single-unit vasoconstrictor impulses. There was a significant correlation between s-MSNA and MSNA, and results of variability studies were similar. The EHT-1 and EHT-2/3 groups had greater s-MSNA and MSNA than did the matched NT group (always P<0. 01). The HN group also had greater s-MSNA and MSNA than did the NT group (mean+/-SEM; 43+/-5 vs 29+/-2 impulses/100 beats, P<0.05; 36+/-4 vs 24+/-2 bursts/100 beats, P<0.05). In addition, the EHT-1 group had significantly greater s-MSNA than did the EHT-2/3 group (63+/-6 vs 51+/-3 impulses/100 beats, P<0.05), which could not be demonstrated with MSNA bursts. Conclusions-Quantification from single vasoconstrictor units has provided additional evidence in established essential hypertension of increased central sympathetic output. Furthermore, in the mild or early stages of hypertension, this technique has provided new evidence of augmented sympathetic output compared with more severe hypertension.
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PMID:Single-unit sympathetic discharge : quantitative assessment in human hypertensive disease. 1049 75

Previous studies have demonstrated that elevated plasma leptin concentrations are associated with essential hypertension. It has also recently been shown that leptin plays a promoting role in angiogenesis, and the vascular endothelium expresses the long form of leptin receptor. Those data led us to hypothesize that leptin might contribute to end-organ damage in hypertension. Thus, in the present study we evaluated the relationship between plasma leptin concentrations and hypertensive retinopathy (HR). One hundred and eleven patients newly diagnosed with essential hypertension [EHT; mean age, 43.5 +/-10.7 yr; body mass index (BMI), 28.1 +/- 4.4 kg/m2; male/female ratio, 71/40] and 79 healthy normotensive control subjects (NT; mean age, 43.6 +/- 9.2 yr; BMI, 28.2 +/- 3.3 kg/m2; male/female ratio, 50/29) were enrolled in the study. For the assessment of retinopathy according to the Keith-Wagener classification, direct and indirect ophthalmoscopy were performed in all subjects after dilatation of the pupils. Plasma leptin levels were significantly higher in EHT (11.8 +/- 11.1 ng/mL) than in NT (7.2 +/- 5.1 ng/mL) (P = 0.003). Plasma leptin concentrations were strongly correlated with BMI in both EHT (r = 0.45; P = 0.001) and NT (r = 0.38; P = 0.001) groups. Plasma leptin in patients with grade 2 HR (24.8 +/- 15.8 ng/mL; n = 22) was significantly higher than that in patients with grade 1 HR (16.1 +/- 4.9 ng/mL; n = 29; P = 0.001), grade 0 HR (5.1 +/- 3.1 ng/mL; n = 60; P = 0.001), and NT (P = 0.001). Plasma leptin in patients with grade 1 HR was also significantly higher than that in patients without retinopathy (P = 0.001) or in NT (P = 0.001). The estimated threshold of plasma leptin concentration for HR was 10.2 ng/mL. This critical leptin level served largely to separate patients with retinopathy from those without retinopathy. In summary, our results show that plasma leptin concentrations increase progressively with higher grades of hypertensive retinopathy even after correction for BMI, suggesting that a critical leptin level is needed for the development of retinopathy. Elevated concentrations of plasma leptin might be secondary to release of leptin by the vascular endothelium damaged by high blood pressure, as an epiphenomenon. However, a pathogenic role for leptin in hypertensive retinopathy cannot be excluded.
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PMID:Is leptin associated with hypertensive retinopathy? 1069 Aug 76

The clinical features of preeclampsia have been traditionally ascribed to a generalized vascular endothelial cell dysfunction. The present study investigates the effect of sera from preeclamptic women and normal pregnancy on the metabolism of intracellular Ca(2+) concentration ([Ca(2+)](i)) in normal cultured vascular smooth muscle cells (VSMC). Sera were obtained from normotensive pregnant women (NTP) (n = 17), preeclamptic women (PE) (n = 15), pregnant women with chronic (essential) hypertension (pregnant EHT) (n = 8), non-pregnant women with essential hypertension (non-pregnant EHT) (n = 12), and age-matched non-pregnant normotensive women (NNP) (n = 18). Serum (10%) was applied to both primary cultures of rat aortic smooth muscle cells and to the A-10 vascular muscle cell line. Levels of [Ca(2+)](i) were determined fluorometrically. After a 4-h incubation with serum, basal [Ca(2+)](i) was not significantly altered. However, compared with normal pregnant sera, PE sera markedly reduced hormonally induced Ca(2+) transients. Thus, following acute stimulation of rat VSMC (primary cultures) with 10(-8)M angiotensin II, peak [Ca(2+)](i) responses (% increment over baseline) were 443 +/- 22, 184 +/- 18, 259 +/- 12, 274 +/- 23, and 255 +/- 15% in NTP, PE, pregnant EHT, non-pregnant EHT, and NNP, respectively (P <0.01 PE versus NTP, P <0.05 PE versus NNP and pregnant and non-pregnant EHT). These effects of sera on [Ca(2+)](i) were qualitatively reproduced in platelets obtained from healthy volunteers. Also, depolarization-activated Ca(2+) influx in VSMC was affected by the different sera groups in a manner similar to that seen with hormonally induced [Ca(2+)](i) responses. The altered [Ca(2+)](i) changes by PE sera disappeared 5 wk after delivery. The effect of the different sera groups on hormonally triggered Ca(2+) transients in normal VSMC, as well as the normalization of [Ca(2+)](i) responses after delivery, suggest the presence of a circulating serum factor in PE. Inasmuch as [Ca(2+)](i) is the major determinant of VSMC tone, it is possible that consequent to the attenuation of [Ca(2+)](i) responses, this putative circulating factor counterbalances the intense vasoconstriction in PE.
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PMID:Differential effects of sera from normotensive and hypertensive pregnant women on Ca(2+) metabolism in normal vasular smooth muscle cells. 1086 74

The human renin gene (REN) is a good candidate in studies aimed at unravelling the genetic basis of essential hypertension and stroke. We previously established that both a BglI and an MboI dimorphisms (located respectively in the first and ninth introns of the REN gene) were associated with essential hypertension in a population of hyperlipidaemic US subjects. In this association (retrospective case-control) study, we investigated the haplotype distribution of alleles defined by the combination of REN BglI and MboI dimorphic sites in 329 hyperlipidaemic US Caucasian subjects referred to UCSF Medical Center (140 hypertensives, 141 normotensives, and 48 hypertensive patients who had suffered a stroke). A statistically significant association was found between alleles determined by both (BglI(-)/MboI(+)) and (BglI(+)/MboI(+)) haplotypes and clinical diagnosis of EHT (combined odds ratios, OR = 3.35, corrected P < 10(-7)). Haplotypes (-,+) and (+,+) were also found to be associated with clinical diagnosis of stroke (OR = 4.31, P < 10(-7)). These associations do not occur through the effects of classical risk factors related to lipid, lipoprotein and apolipoprotein levels. We conclude that variations of the REN (or of a nearby) gene that may be in linkage disequilibrium with REN (BglI(-)/MboI(+)) and (BglI(+)/MboI(+)) alleles could play a role in contributing to increased individual's genetic susceptibility to EHT and to stroke. Journal of Human Hypertension(2001) 15, 49-55
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PMID:Haplotypes of the human renin gene associated with essential hypertension and stroke. 1122 2

Candidate genes offer one approach to the identification of the genetic susceptibility to hypertension. A common gene variant of the low-density lipoprotein (LDL) receptor gene (LDLR) that affects plasma LDL metabolism within the normolipidaemic range, may be such a candidate gene. A common mutation of LDLR, C1773T, was associated with lipid metabolism such that the T1773 allele increased plasma LDL levels in a Caucasian population. The present study examined whether C1773T/LDLR was associated with essential hypertension in a Japanese population. Subjects with essential hypertension (EHT, n = 300) with a family history of hypertension, and controls (NT, n = 310, sex- and age-matched with EHT) were recruited from among out-patients at Osaka University Hospital. A C1773T substitution at codon 570 in LDLR was determined using PCR-Hinc II-RFLP. It was revealed that the C1773 allele was significantly more frequent (0.89) among hypertensive patients (chi2 = 9.58, P < 0.01) than normotensives (0.83), the calculated odds ratio being 1.7 (95% CI: 1.2-2.4). The effect of the T1773 allele on increasing cholesterol was significant in normotensives without antihyperlipidaemic medication, but not in hypertensives. After adjustments of confounding factors, the estimated odds ratio for hypertension in the subjects with C1773 homozygote increased to 2.1 (95% CI: 1.3-3.5), suggesting that this polymorphism is an independent risk factor for hypertension. Our results show that the C1773 mutant of LDLR increases susceptibility to hypertension, but not via hypercholesterolaemia.
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PMID:A common mutation of low-density lipoprotein receptor gene is associated with essential hypertension among Japanese. 1131 92

Lipocalin-type prostaglandin D synthase (L-PGDS) reportedly well predicts cardiovascular injuries in humans. However, little is known about the implications of L-PGDS in hypertension. In the present study, we investigated the alterations of serum and urinary L-PGDS in hypertensive patients with or without renal dysfunction. A total of 111 patients with hypertension (EHT; 65 with normoalbuminuria, 23 with microalbuminuria, 12 with macroalbuminuria, 11 with renal failure) and 102 normotensive, nomoalbuminuric subjects (NT) were studied. L-PGDS was measured by enzyme-linked immunosorbent assay, and L-PGDS in the kidney was localized using immunohistochemical methods. Blood pressure was higher in EHT groups than in the NT group (P<0.0001). There were no differences in age, gender, BMI, TC, TG, and HbA1c levels among the groups. Serum creatinine and urinary albumin levels were higher in the group with renal failure. Serum levels of L-PGDS were increased in EHT with normoalbuminuria, as compared with NT (0.88 +/- 0.05 versus 0.65 +/- 0.02 microg/mL; P<0.001). Serum levels of L-PGDS increased with the renal function worsened and positively correlated with serum creatinine, particularly in patients with renal impairments (r=0.76, P<0.0001). Similarly, the urinary L-PGDS excretions in EHT with normoalbuminuria were higher than that in NT (2.31 +/- 0.29 versus 1.16 +/- 0.14 mg/gCr, P<0.001), whereas there were no differences in urinary albumin excretion between the 2 groups. Moreover, urinary L-PGDS excretion increased dramatically with an increase in albuminuria or proteinuria. L-PGDS was stained in the tubules and the interstitium of the kidney in nephrosclerosis. In conclusion, patients with hypertension exhibited a higher level of L-PGDS in serum and urine, and this became increasingly obvious along with advance in renal dysfunction. These data suggest that L-PGDS metabolism is related to blood pressure and kidney injuries associated with hypertension.
Hypertension 2002 Feb
PMID:Lipocalin-type prostaglandin d synthase in essential hypertension. 1188 88