UMLS:C0020538 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) show the synthetic phenotype and exaggerated growth in comparison with VSMCs from normotensive Wistar-Kyoto (WKY) rats. We investigated genes associated with the synthetic phenotype and exaggerated growth of VSMCs from SHR by microarray. Expression of 1300 transcripts was evaluated by microarray with total mRNA extracted from mid-layer aortic smooth muscle of 3-week-old SHR/Izumo and WKY/Izumo rats. mRNAs encoding sodium-dependent neurotransmitter transporter, epidermal growth factor precursor, EEF2, leptin receptor long-isoform b, clathrin assembly protein short form, and preprocomplement 3 (pre-pro-C3) were expressed only in aortic smooth muscle from SHR by microarray and by reverse-transcription polymerase chain reaction analysis. Pre-pro-C3 mRNA was detected only in cultured VSMCs from SHR. Exogenous C3 changed VSMCs to the synthetic phenotype. Antisense oligodeoxynucleotides (ODN) to C3 reduced the higher level of DNA synthesis in VSMCs from SHR. Antisense ODN to C3 increased expression of SM22alpha mRNA and decreased expression of osteopontin and matrix Gla mRNAs. It also decreased expression of growth factor mRNAs in VSMCs from SHR. In conclusion, we have shown that C3, independent of other complement molecules, has direct effects on the phenotype of VSMCs and stimulates growth of these cells. C3 is produced only by VSMCs from SHR. Therefore, C3 may be the gene underlying the synthetic phenotype and exaggerated growth of VSMCs from SHR. C3 may be a new target for the treatment of hypertension.
Hypertension 2004 Jul
PMID:Complement 3 is involved in the synthetic phenotype and exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats. 1512 74

This study examined sensory nerves associated with mesenteric arteries and veins in sham and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Reactivity of arteries and veins to substances released from sensory nerves was also studied in vitro using computer-assisted video microscopy. Co-localization of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactivity (ir) was used to evaluate perivascular sensory nerves. Radioimmunoassay was used to quantify SP- and CGRP-ir content. Immunohistochemical studies revealed a plexus of SP/CGRP-ir nerves associated with arteries and veins. The intensity of SP-ir, but not CGRP-ir labeling was greater in arteries and veins from DOCA-salt compared to sham rats. RIA measurements revealed that the CGRP-ir content of arteries and veins was higher than the SP-ir content but there was a significant increase in SP-ir, but not CGRP-ir, content in arteries and veins from DOCA-salt rats. SP (0.03-1 microM) contracted veins and the NK-3 receptor agonist, senktide, mimicked this effect. There were no differences in SP or senktide reactivity of veins from sham or DOCA-salt rats. SP, but not senktide, relaxed KCl (40 mM) preconstricted arteries. CGRP (0.3 microM), acetylcholine (10 microM) and capsaicin (1 microM) relaxed KCl-preconstricted arteries and veins. The NK-1 receptor agonist, substance P methyl ester relaxed arteries but not veins. These data indicate that DOCA-salt hypertension is associated with upregulation of SP content in perivascular nerves. NK-3 receptors mediate venoconstriction which is unchanged in DOCA-salt hypertension. Increased release of SP from perivenous nerves might contribute to the increased venomotor tone in DOCA-salt hypertension.
...
PMID:Increased substance P content in nerve fibers associated with mesenteric veins from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. 1629 89

1 Effects of intrathecally (i.t.) injected tachykinin NK-1 and -3 receptor agonists and antagonists were measured on mean arterial blood pressure (MAP) and heart rate (HR) in awake unrestrained spontaneously hypertensive rats (SHR,15-week-old) and age-matched Wistar Kyoto rats (WKY). Quantitative in vitro autoradiography was also performed on the lower thoracic spinal cord of both strains and Wistar rats using specific radioligands for NK-1 receptor ([(125)I]HPP[Arg(3),Sar(9),Met(O(2))(11)]SP (3-11)) and NK-3 receptor ([(125)I]HPP-Asp-Asp-Phe-N-MePhe-Gly-Leu-Met-NH(2)). 2 The NK-1 agonist [Sar(9),Met(O(2))(11)]SP (650 and 6500 pmol) decreased MAP and increased HR in WKY. The fall in MAP was blunted in SHR and substituted by increases in MAP (65-6500 pmol) and more sustained tachycardia. The NK-3 agonist senktide (6.5-65 pmol) evoked marked increases in MAP and HR (SHR>>>WKY), yet this response was rapidly desensitized. Cardiovascular effects of [Sar(9),Met(O(2))(11)]SP (650 pmol) and senktide (6.5 pmol) were selectively blocked by the prior i.t. injection of LY303870 (NK-1 antagonist, 65 nmol) and SB235375 (NK-3 antagonist, 6.5 nmol), respectively. Antagonists had no direct effect on MAP and HR in both strains. 3 Densities of NK-1 and -3 receptor binding sites were significantly increased in all laminae of the spinal cord in SHR when compared to control WKY and Wistar rats. The dissociation constant was however not affected in SHR for both NK-1 (K(d)=2.5 nM) and NK-3 (K(d)=5 nM) receptors. 4 Data highlight an upregulation of NK-1 and -3 receptor binding sites in the thoracic spinal cord of SHR that may contribute to the hypersensitivity of the pressor response to agonists and to the greater sympathetic activity seen in this model of arterial hypertension.
...
PMID:Upregulation of tachykinin NK-1 and NK-3 receptor binding sites in the spinal cord of spontaneously hypertensive rat: impact on the autonomic control of blood pressure. 1649 Oct 95

Sexual dysfunction is a highly prevalent condition in ageing men that considerably affects their quality of life, although it is a frequently neglected aspect of healthcare. The main predictors of sexual dysfunction are age and cardiovascular comorbidities such as hypertension, heart disease, hypercholesterolaemia and diabetes. Recently, the severity of lower urinary tract symptoms (LUTS) has also been identified as a crucial risk factor for sexual dysfunction, independent of age and comorbidities. Despite the increased prevalence of sexual dysfunction with age, health-related problems and psychological factors, there is evidence that many older men remain sexually active. Currently available self-administered questionnaires assessing male sexual dysfunction focus almost exclusively on erectile function. There is evidence from recent large-scale epidemiological studies that ejaculatory dysfunction (EjD) is almost as prevalent as erectile dysfunction (ED), affecting nearly half of men aged > or = 50 years. Other domains such as orgasm, desire, and satisfaction with sex life are important and should be considered. There is thus a need to develop and validate more comprehensive and multidimensional instruments for assessing sexual dysfunction in ageing men. A new instrument, the Male Sexual Health Questionnaire (MSHQ), was developed and validated to assess these specific aspects of male sexual dysfunction . It consists of a 25-item self-administered questionnaire including three core domains (erection, ejaculation, satisfaction with sex life) and additional items related to sexual activity, desire and bother related to sexual dysfunction. The MSHQ scale has excellent psychometric properties and is well suited for use in clinical and research settings. A short form of the MSHQ scale is currently under development.
...
PMID:Assessment of sexual dysfunction in patients with benign prostatic hyperplasia. 1650 51

Members of the WNK family of serine/threonine kinases have been implicated as important modulators of salt homeostasis, regulating the balance between renal sodium reabsorption and potassium excretion. Gain-of-expression mutations in the WNK1 gene uncouple Na(+) and K(+) balance and cause a familial disorder of diminished renal potassium excretion, excessive sodium retention, and hypertension (pseudohypoaldosteronism type II or Gordon's syndrome). Alternative splicing of the WNK1 gene produces a kidney-specific short form of WNK1 (KS-WNK1) and a more ubiquitous long form (L-WNK1), but it is not clear how either of these isoforms influence renal potassium excretion. Here we demonstrate that KS-WNK1 and L-WNK1 converge in a pathway to regulate the renal outer-medullary K(+) channel, Kir1.1. Reconstitution studies in Xenopus oocytes reveal that L-WNK1 significantly inhibits Kir1.1 by reducing cell surface localization of the channel. A catalytically inactive L-WNK1 mutant has no inhibitory effect on Kir1.1, indicating that channel inhibition depends on kinase activity. KS-WNK1, lacking an intact kinase domain, does not directly alter Kir1.1. Instead, KS-WNK1 negatively regulates L-WNK1 to release Kir1.1 from inhibition. Acute dietary potassium loading increases the relative abundance of KS-WNK1 to L-WNK1 transcript and protein in the kidney, indicating that physiologic up-regulation of Kir1.1 activity involves a WNK1 isoform switch and KS-WNK1-mediated release from L-WNK1 inhibition. Thus, these observations provide evidence for the physiological regulation of Na(+) and K(+) balance by a kinase isoform switch mechanism.
...
PMID:WNK1 kinase isoform switch regulates renal potassium excretion. 1670 64

Surgical results, economic consequences, and shortterm health of obese patients were evaluated before and after bariatric surgery. Of 35 patients in Mayo Health Plan Arizona eligible for bariatric surgery and scheduled for gastric restriction with Roux-en-Y gastrojejunostomy, 22 (7 men, 15 women) completed pre- and postoperative (6- and 12-mo) short form (SF)-12 Health Surveys. Nineteen patients had open bariatric procedures and 3 had laparoscopic procedures. Comorbid conditions, hospital course, weight loss, and complications were examined. Health care utilization (actual dollars paid by plan) for the preceding year and at 1- and 2-yr follow-up were compared. Major comorbid conditions included diabetes mellitus or impaired fasting glucose, hyperlipidemia, sleep apnea, and hypertension. Mean length of hospital stay was 4.8 d after open procedures and 2 d after laparoscopic procedures. No serious operative or postoperative complications occurred. From a baseline average body mass index (BMI) of 51.9, the 6- and 12-mo BMI averages were 39.6 (23.7% decrease) and 35.3 (32% decrease), respectively. Both physical and mental status improved. From baseline, physical health changed 18 and 21.2 points at 6 and 12 mo, respectively (p < 0.001), and mental health changed 9.3 points at each interval (p =0.003). Each postoperative year, resource utilization decreased (mean= $1300 per patient). Our findings of good surgical outcomes, significant weight loss, improved health status, and potential financial savings in this small sample may help patients, insurers, and self-funded employer groups evaluate the appropriateness of bariatric procedures.
...
PMID:Outcomes, health status, and medical resource utilization after bariatric surgery. 1678 80

Bone morphogenetic protein (BMP) signals regulate the growth and differentiation of diverse lineages. The association of mutations in the BMP type II receptor (BMPRII) with idiopathic pulmonary arterial hypertension suggests an important role of this receptor in vascular remodeling. Pulmonary artery smooth muscle cells lacking BMPRII can transduce BMP signals using ActRIIa (Activin type II receptor). We investigated whether or not BMP signaling via the two receptors leads to differential effects on vascular smooth muscle cells. BMP4, but not BMP7, inhibited platelet-derived growth factor-activated proliferation in wild-type pulmonary artery smooth muscle cells, whereas neither ligand inhibited the growth of BMPRII-deficient cells. Adenoviral gene transfer of BMPRII enabled BMP4, as well as BMP7, to inhibit proliferation in BMPRII-deficient cells. BMP-mediated growth inhibition was also reconstituted by the BMPRII short isoform, lacking the C-terminal domain present in the long form. BMP4, but not BMP7, induced the expression of osteoblast markers in wild-type cells, whereas neither ligand induced these markers in BMPRII-deficient cells. Overexpression of short or long forms of BMPRII in BMPRII-deficient cells enabled BMP4 and BMP7 to induce osteogenic differentiation. Although signaling via BMPRII or ActRIIa transiently activated SMAD1/5/8, only BMPRII signaling led to persistent SMAD1/5/8 activation and sustained increases in Id1 mRNA and protein expression. Pharmacologic blockade of BMP type I receptor function within 24 h after BMP stimulation abrogated differentiation. These data suggest that sustained BMP pathway activation, such as that mediated by BMPRII, is necessary for growth and differentiation control in vascular smooth muscle.
...
PMID:Bone morphogenetic protein (BMP) type II receptor is required for BMP-mediated growth arrest and differentiation in pulmonary artery smooth muscle cells. 1804 51

Mutations in the bone morphogenetic protein receptor type II (BMPrII) gene have been implicated in the development of familial pulmonary artery hypertension (PAH). The function of BMP signal transduction within the pulmonary vasculature and the role BMPrII mutations have in the development of PAH are incompletely understood. We used the monocrotaline (MCT) model of PAH to examine alterations in Smad signal transduction pathways in vivo. Lungs harvested from Sprague-Dawley rats treated with a single 60-mg/kg intraperitoneal (IP) injection of MCT were compared to saline-treated controls 2 weeks following treatment. Smad 4 was localized by immunohistochemistry to endothelial nuclei of the intra-acinar vessels undergoing remodeling. Smad 4, common to both BMP and transforming growth factor beta (TGFbeta) signaling, and BMP-specific Smad 1 were significantly decreased in western blot from whole lungs of treated animals, while no change was found for TGFbeta-specific Smad 2. MCT-treated rats also had increased expression of phosphorylated Smad 1 (P-Smad 1) but not phosphorylated Smad 2 (P-Smad 2). There was a decrease in the expression of the full BMPrII protein but not its short form variant in MCT-treated rat lungs. The type I receptor Alk1 had increased expression. Collectively, our data indicate that vascular remodeling in the MCT model is associated with alterations in BMP receptors and persistent endothelial Smad 1 signaling.
...
PMID:Smad signaling in the rat model of monocrotaline pulmonary hypertension. 1836 43

Studies suggested that hypertension was associated with impaired health-related quality of life and it is important to find a proper and feasible management of hypertension in the community. This study evaluates the effect of a tailored target intervention on influence factors of quality of life in Chinese patients with hypertension. A cross-sectional survey was carried out to investigate 644 patients with hypertension by using the Chinese version of the short form-36, and 195 patients were screened out to participate in the tailored target intervention. Multivariate linear regression analyses showed that age, gender, educational level, high intake of fried food, household income, attitude, knowledge, blood pressure, symptoms, serious events during the past year, duration of hypertension, and number of taking anti-hypertensive medicine were significantly correlated with quality of life. Grade-based management by community physicians and physical exercise had a positive effect on quality of life. After the 6-month intervention, the control rate of hypertension was increased from 32.0% to 39.4%, and the mean systolic and diastolic blood pressure values were significantly decreased to 137.2 and 85.7 mmHg vs. 140.9 and 87.6 mmHg at baseline, respectively. The intervention program resulted in overall improvement on total score of quality of life and mean scores of all the domains except social functioning in patients with hypertension. In view of the influence factors of quality of life, taking the tailored target intervention could not only improve the quality of life of hypertensive patients, but also effectively increase the control rate of hypertension.
...
PMID:A tailored target intervention on influence factors of quality of life in Chinese patients with hypertension. 1917 61

WNK kinases are serine-threonine kinases with an atypical placement of the catalytic lysine. WNK1, the first member discovered, has multiple alternatively spliced isoforms, including a ubiquitously expressed full-length long form (L-WNK1) and a kidney-specific form (KS-WNK1) predominantly expressed in the kidney. Intronic deletions of WNK1 that increase WNK1 transcript cause pseudohypoaldosteronism type 2, an autosomal-dominant disease characterized by hypertension and hyperkalemia. L-WNK1 inhibits renal K(+) channel ROMK, likely contributing to hyperkalemia in PHAII. Previously, we reported that KS-WNK1 by itself has no effect on ROMK1 but antagonizes L-WNK1-mediated inhibition of ROMK1. Amino acids 1-253 of KS-WNK1 (KS-WNK1(1-253)) are sufficient for reversing the inhibition of ROMK1 caused by L-WNK1(1-491). Here, we further investigated the mechanisms by which KS-WNK1 counteracts L-WNK1 regulation of ROMK1. We reported that two regions of KS-WNK1(1-253) are involved in the antagonism of L-WNK1; one includes the first 30 amino acids unique for KS-WNK1 encoded by the alternatively spliced initiating exon 4A, and the other is equivalent to the autoinhibitory domain (AID) of L-WNK1. Mutations of two phenylalanine residues known to be critical for autoinhibitory function of AID abolish the ability of the AID region of KS-WNK1 to antagonize L-WNK1. To examine the physiological role of KS-WNK1 in the regulation of renal K(+) secretion, we generated transgenic mice that overexpress amino acids 1-253 of KS-WNK1 under the control of a kidney-specific promoter. Transgenic mice have lower serum K(+) levels and higher urinary fractional excretion of K(+) compared with wild type littermates despite the same amount of daily urinary K(+) excretion. Moreover, transgenic mice (compared with wild type littermates) displayed a higher abundance of ROMK on the apical membrane of distal nephron. Thus, KS-WNK1 is an important physiological regulator of renal K(+) excretion, likely through its effects on the ROMK1 channel.
...
PMID:Regulation of ROMK channel and K+ homeostasis by kidney-specific WNK1 kinase. 1924 42

<< Previous 1 2 3 4 Next >>