muramidase and Hypertension

The potential usefulness of analysis of the salivary secretions in diagnosis and prognosis is beginning to be explored in depth. The preliminary work already undertaken indicates that modern methods applied to this secretion may provide information that is different from that obtained in other body fluids. Saliva is collected at the point of its manufacture and, therefore, is unaffected by collection or storage in the body. It is the product both of protein synthesis within the glands and of most of the known water and electrolyte exchange mechanisms. Salivary composition is affected by both autonomic and hormonal stimuli. As the specific influence of each of these factors is better understood, studies of this fluid will provide important clues to the understanding of disease and the evaluation of therapy. There are few places in the body where it is possible directly, utilizing a non-invasive technique, to examine the product of a large number of important biological processes. It is obvious that careful handling of collection and analytic techniques are essential if these secretions are to be utilized. Future investigations in clinical situations should take full advantage of the strong base of knowledge of the physiology of these glands. Development of this field depends on careful clinical investigations designed to make full use of our current knowledge.

Topics: Amylases; Blood Proteins; Cystic Fibrosis; Dental Caries; Digitalis Glycosides; Electrolytes; Glycoproteins; Humans; Hypertension; Immunoglobulin A, Secretory; Mouth Diseases; Muramidase; Parotid Gland; Physical Stimulation; Saliva; Salivary Gland Diseases; Salivary Proteins and Peptides; Secretory Rate; Specimen Handling; Submandibular Gland

Angiotensin-converting enzyme (ACE) inhibitors are important agents in blood pressure (BP) management. It was recently shown that the egg-protein hydrolysate NWT-03 inhibited ACE in Zucker diabetic fatty rats. We therefore designed a dose-finding study to assess the effects of 1, 2 and 5 g NWT-03 on daytime, 36-h, and night-time systolic and diastolic BP (SBP and DBP) in ninety-two generally healthy subjects with normal BP (n 29), high-normal BP (n 34) or mild hypertension (n 29). The study had a cross-over design with six treatment arms (1 g NWT-03 or placebo in period 1 and placebo or 1 g NWT-03 in period 2, 2 g NTW-03 or placebo in period 1 and placebo or 2 g NWT-03 in period 2, or 5 g NTW-03 or placebo in period 1 and placebo or 5 g NTW-03 in period 2). A comparable number of subjects from each BP class were included in each study arm. Duration of both treatments in each arm was 7 d, separated by 5-d wash-out periods. BP was measured with an ambulatory BP monitor before and after the treatments. In mild-hypertensive subjects, 2 g NWT-03 significantly decreased daytime SBP (7·9 mmHg; P=0·006), daytime DBP (4·2 mmHg; P=0·009), 36-h SBP (6·9 mmHg; P=0·015) and 36-h DBP (3·5 mmHg; P=0·035) compared with placebo subjects. In addition, in mild-hypertensive subjects, 5 g NWT-03 significantly decreased night-time SBP (14·8 mmHg; P=0·008) and night-time DBP (8·4 mmHg; P=0·020) compared with that in placebo subjects. To conclude, we found that 2 g NWT-03 lowered daytime and 36-h BP in subjects with mild hypertension, and 5 g NWT-03 lowered night-time BP in subjects with mild hypertension. As no dose-response relationship was evident, these results should be interpreted with care, and additional studies are needed.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Cross-Over Studies; Dietary Supplements; Female; Humans; Hypertension; Male; Middle Aged; Muramidase; Prehypertension; Protein Hydrolysates; Reproducibility of Results; Severity of Illness Index

Whereas circulating levels of C-reactive protein (CRP) have been associated with, for example, arterial stiffness, subclinical atherosclerosis and metabolic syndrome, other inflammatory biomarkers with potential interest for these conditions may not be measurable systemically. The predictive value of salivary biomarkers in these contexts has remained largely unexplored. The aim of the present study was to establish the association of different salivary biomarkers of inflammation with subclinical cardiovascular disease.. Two hundred and fifty-nine individuals were included in the study. Saliva and plasma samples were collected, and each individual underwent carotid ultrasound and measures of pulse wave velocity and blood pressure. Medical history of previous cardiovascular disease, current medications and smoking were collected by questionnaire.. Salivary levels of CRP, leukotriene B4 (LTB4), prostaglandin E2 (PGE2), matrix metalloproteinase 9 (MMP-9), creatinine and lysozyme were measured. Salivary levels of CRP were significantly correlated with plasma levels (r = 0.73, P < 0.0001). In an age-adjusted and sex-adjusted analysis, salivary CRP was significantly and positively correlated with mean arterial blood pressure, pulse pressure, pulse wave velocity, BMI, metabolic syndrome, waist-to-hip ratio and intima-media thickness. Increasing age and sex-adjusted salivary CRP tertiles were in addition associated with carotid plaques. In a multivariate analysis, CRP and MMP-9 were associated with intima-media thickness, LTB4 and PGE2 with arterial stiffness, and lysozyme with hypertension.. Saliva may represent an alternative mean for evaluation of cardiovascular risk.

Topics: Aged; Atherosclerosis; Biomarkers; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Creatinine; Dinoprostone; Female; Humans; Hypertension; Inflammation Mediators; Leukotriene B4; Male; Matrix Metalloproteinase 9; Metabolic Syndrome; Middle Aged; Muramidase; Pulse Wave Analysis; Risk Factors; Saliva; Vascular Stiffness; Waist-Hip Ratio

Angiotensin II (ATII), a potent vasoconstrictor, causes hypertension, promotes infiltration of myelomonocytic cells into the vessel wall, and stimulates both vascular and inflammatory cell NADPH oxidases. The predominant source of reactive oxygen species, eg, vascular (endothelial, smooth muscle, adventitial) versus phagocytic NADPH oxidase, and the role of myelomonocytic cells in mediating arterial hypertension have not been defined yet.. Angiotensin II (1 mg · kg(-1) · d(-1) for 7 days) increased the number of both CD11b(+)Gr-1(low)F4/80(+) macrophages and CD11b(+)Gr-1(high)F4/80(-) neutrophils in mouse aorta (verified by flow cytometry). Selective ablation of lysozyme M-positive (LysM(+)) myelomonocytic cells by low-dose diphtheria toxin in mice with inducible expression of the diphtheria toxin receptor (LysM(iDTR) mice) reduced the number of monocytes in the circulation and limited ATII-induced infiltration of these cells into the vascular wall, whereas the number of neutrophils was not reduced. Depletion of LysM(+) cells attenuated ATII-induced blood pressure increase (measured by radiotelemetry) and vascular endothelial and smooth muscle dysfunction (assessed by aortic ring relaxation studies) and reduced vascular superoxide formation (measured by chemiluminescence, cytochrome c assay, and oxidative fluorescence microtopography) and the expression of NADPH oxidase subunits gp91(phox) and p67(phox) (assessed by Western blot and mRNA reverse-transcription polymerase chain reaction). Adoptive transfer of wild-type CD11b(+)Gr-1(+) monocytes into depleted LysM(iDTR) mice reestablished ATII-induced vascular dysfunction, oxidative stress, and arterial hypertension, whereas transfer of CD11b(+)Gr-1(+) neutrophils or monocytes from gp91(phox) or ATII receptor type 1 knockout mice did not. CONCLUSIONS- Infiltrating monocytes with a proinflammatory phenotype and macrophages rather than neutrophils appear to be essential for ATII-induced vascular dysfunction and arterial hypertension.

Topics: Angiotensin II; Animals; CD11b Antigen; Endothelium, Vascular; Gene Expression; Hypertension; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Monocytes; Muramidase; Muscle, Smooth, Vascular; Neutrophils; Nitric Oxide; Oxidative Stress; Reactive Oxygen Species; Receptors, Chemokine; Respiratory Burst; Vasculitis; Vasoconstrictor Agents

One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs) have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns-independent component analysis-to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify major trans-acting regulators. We detected three genomic regions significantly associated with co-regulated gene modules. Association of these loci with multiple expression traits was replicated in Cardiogenics, an independent study in which expression profiles of monocytes were available in 758 subjects. The locus 12q13 (lead SNP rs11171739), previously identified as a type 1 diabetes locus, was associated with a pattern including two cis eQTLs, RPS26 and SUOX, and 5 trans eQTLs, one of which (MADCAM1) is a potential candidate for mediating T1D susceptibility. The locus 12q24 (lead SNP rs653178), which has demonstrated extensive disease pleiotropy, including type 1 diabetes, hypertension, and celiac disease, was associated to a pattern strongly correlating to blood pressure level. The strongest trans eQTL in this pattern was CRIP1, a known marker of cellular proliferation in cancer. The locus 12q15 (lead SNP rs11177644) was associated with a pattern driven by two cis eQTLs, LYZ and YEATS4, and including 34 trans eQTLs, several of them tumor-related genes. This study shows that a method exploiting the structure of co-expressions among genes can help identify genomic regions involved in trans regulation of sets of genes and can provide clues for understanding the mechanisms linking genome-wide association loci to disease.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Celiac Disease; Diabetes Mellitus, Type 1; Female; Gene Expression Profiling; Gene Expression Regulation; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Genome, Human; Humans; Hypertension; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Monocytes; Muramidase; Polymorphism, Single Nucleotide; Proteins; Quantitative Trait Loci; Ribosomal Proteins; Transcription Factors

Salivary lysozyme (SLZ) is a proteolytic enzyme secreted by oral leucocytes and contains a domain that has an affinity to advanced glycation end products (AGE). Thus, we hypothesized that SLZ would be associated with metabolic syndrome (metS), a pro-inflammatory state.. Utilizing cross-sectional data from 250 coronary artery disease (CAD) and 250 non-CAD patients, the association of SLZ with metS was tested by logistic regression analyses controlling for age, sex, smoking, total cholesterol and C-reactive protein (CRP) levels. The analyses were stratified by CAD status to control for the possible effects of CAD.. MetS was found in 122 persons. The adjusted odds ratio (OR) for metS associated with the highest quartile of SLZ was 1.95 with 95% confidence interval (CI) 1.20-3.12, p-value=0.007, compared with the lower three quartiles combined. Among the 40 subjects with metS but without CAD, the OR was 1.63 (CI: 0.64-4.15, p=0.31), whereas in the CAD group, SLZ was significantly associated with metS [OR=1.96 (1.09-3.52), p=0.02]. In both subgroups, CRP was not significantly associated with metS.. SLZ was significantly associated with metS (OR=1.95) independent of CRP level. Future longitudinal research is warranted.

Topics: Age Factors; Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Case-Control Studies; Cholesterol; Cholesterol, HDL; Cohort Studies; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged; Muramidase; Saliva; Salivary Proteins and Peptides; Sex Factors; Smoking; Triglycerides

Although the etiology of essential hypertension is not clearly understood, endothelial dysfunction from chronic infection and/or impaired glucose metabolism may be involved. We hypothesized that salivary lysozyme, a marker for oral infection and hyperglycemia, might display a significant relationship with hypertension, an early stage of cardiovascular disease. Logistic regression analyses of the Kuopio Oral Health and Heart Study demonstrated that persons with higher lysozyme levels were more likely to have hypertension, after adjustment for age, gender, smoking, BMI, diabetes, the ratio of total cholesterol to HDL cholesterol, and C-reactive protein. The exposure to increasing quartiles of lysozyme was associated with adjusted Odds Ratios for the outcome, hypertension, 1.00 (referent), 1.25, 1.42, and 2.56 (linear trend p < 0.003). When we restricted the sample to the individuals without heart disease (N = 250), we observed a non-significant trend for increasing odds. Our hypothesis--"high salivary lysozyme levels are associated with the odds of hypertension"--was confirmed.

Topics: Aged; Biomarkers; Case-Control Studies; Cohort Studies; Coronary Artery Disease; Cross-Sectional Studies; Female; Finland; Humans; Hyperglycemia; Hypertension; Male; Middle Aged; Muramidase; Odds Ratio; Reference Values; Regression Analysis; Saliva; Statistics, Nonparametric

Topics: Bacteriuria; Glomerular Filtration Rate; Glomerulonephritis; Humans; Hypertension; Kidney Diseases; Muramidase; Pyelonephritis; Uremia; Urinary Calculi

Topics: Adolescent; Adult; Aged; Animals; Chronic Disease; Dogs; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Hypertension; Hypertension, Renal; Immunoelectrophoresis; Kidney Diseases; Male; Middle Aged; Muramidase; Myeloma Proteins; Nephritis, Interstitial; Nephrocalcinosis; Nephrotic Syndrome; Pyelonephritis; Rabbits; Vascular Diseases

Topics: Antibodies; Arteriosclerosis; Blood Vessels; Brain; Cardiovascular Diseases; Cerebrovascular Disorders; Endarteritis; Humans; Hypertension; Muramidase

Topics: Adult; Female; Humans; Hypertension; Kidney Diseases; Muramidase; Pre-Eclampsia; Pregnancy