Metabolic Syndrome Blood Pressure Research Articles

Effects of Omega-3 Fatty Acids Supplementation on Serum Lipid Profile and Blood Pressure in Patients with Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The purpose of this study was to explore the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation on serum lipid profile and blood pressure in patients with metabolic syndrome. We searched PubMed, Web of Science, Embase, and the Cochrane library from database inception to 30 April 2022. This meta-analysis included eight trials with 387 participants. We found that supplementation of n-3 PUFAs has no significant reduction in TC level (SMD = -0.02; 95% CI: -0.22 ~ 0.18, I2 = 23.7%) and LDL-c level in serum (SMD = 0.18; 95% CI: -0.18 ~ 0.53, I2 = 54.9%) of patients with metabolic syndrome. Moreover, we found no significant increase in serum high-density lipoprotein cholesterol level (SMD = 0.02; 95% CI: -0.21 ~ 0.25, I2 = 0%) in patients with metabolic syndrome after consuming n-3 PUFAs. In addition, we found that n-3 PUFAs can significantly decrease serum triglyceride levels (SMD= -0.39; 95% CI: -0.59 ~ -0.18, I2 = 17.2%), systolic blood pressure (SMD = -0.54; 95% CI: -0.86 ~ -0.22, I2 = 48.6%), and diastolic blood pressure (SMD = -0.56; 95% CI: -0.79 ~ 0.33, I2 = 14.0%) in patients with metabolic syndrome. The results from the sensitivity analysis confirmed that our results were robust. These findings suggest that n-3 PUFA supplementation may serve as a potential dietary supplement for improving lipids and blood pressure in metabolic syndrome. Given the quality of the included studies, further studies are still needed to verify our findings.

Metabolic Syndrome and Its Components: A Cross-Sectional Analysis of Its Distribution among Pre- and Post-Menopausal Women from Northern India.

This study aims to determine the prevalence of Metabolic Syndrome (MS) and recognize its abnormal components in pre and postmenopausal women. We also aim to recognize the abnormal components in postmenopausal women with regard to duration since menopause. The cross-sectional study was undertaken among pre- and post-menopausal women between 40 and 65 years. Women with MS were identified as per the modified National Cholesterol Education Program Adult Treatment Panel III. A total of 220 women were enrolled comprising 112 premenopausal and 108 postmenopausal women, the prevalence of MS among them being 33% and 51.85%, respectively. Postmenopausal status was found to be independently associated with MS when adjusted for potential confounders (adjusted odds ratios = 14.77, 95% confidence intervals: 1.77-23.33). All the components were proportionately higher in postmenopausal group, the rise in blood pressure (BP) (P = 0.003) and low high-density lipoprotein (HDL) (0.027) being statistically significant. The risk of MS, abdominal obesity, and high BP were highest in <5 years since menopause and decreased thereafter. The risk for low HDL and high triglyceride increased with the number of years since menopause, reaching the peak level in the 5-9-year group and then decreased while the risk of high fasting blood sugar increased reaching peak in the 10-14 years' group. The prevalence of MS is significantly high in postmenopausal women. Screening of women in premenopausal period will give an opportunity to intervene and prevent the menace of MS in Indian women predisposed to abdominal obesity, insulin resistance, and cardiovascular adverse events.

Влияние синдрома Х на развитие сердечно-сосудистой патологии (обзор литературы)

Metabolic syndrome, also known as syndrome X, is defined by WHO as a pathological condition characterized by abdominal obesity, insulin resistance, hypertension and hyperlipidemia. While there are some differences in definitions adopted by other health organizations, the differences are minor. Successfully defeating infectious diseases, this new noncommunicable disease has become a leading cause of morbidity and mortality not only in the developed world, but also in underdeveloped countries. As highlighted in the literature, multiple factors such as obesity, abnormal lipid profiles and insulin resistance play a key role in the onset of cardiovascular disease. In this brief review, we present an updated hypothesis that insulin resistance and compensatory hyperinsulinemia are major factors in elevated blood pressure in metabolic syndrome and obesity. Obesity is a worldwide epidemic closely linked to the development of type 2 diabetes and CVD. Obesity-related visceral and epicardial obesity are the main causes of heart disease in these individuals. Obesity has a major impact on changes in blood pressure, lipid profile, and factors associated with systemic and vascular inflammation, as well as endothelial dysfunction.

Intra‐Abdominal Lipectomy Reduces Large Arterial Stiffness and Blood Pressure in Metabolic Syndrome

Increased intra‐abdominal (visceral) adipose tissue is a key feature of the metabolic syndrome. Expansion of visceral adipose tissue and the associated altered adipokine profile are linked to the development of hypertension. While reduction in visceral adipose tissue volume offers cardioprotective effects, the mechanisms underlying these effects remain understudied and unclear. In this study, we removed ~90% of visceral adipose tissue (=~5% body weight) by intra‐abdominal lipectomy and assessed large arterial stiffness, large artery structural matrix components, and blood pressure in a metabolic syndrome rat model (JCR:LA‐cp, JCR). Large artery compliance was significantly decreased in JCR vs. normal (Sprague Dawley, SD) rats (75±2% JCR vs. SD (carotid)) with a concomitant significant increase in MMP12‐dependent elastin degradation (3–6 fold vs. SD). Intra‐abdominal lipectomy normalized large artery stiffness, blocked MMP12 activation and reduced elastin degradation in JCR animals (~75% (carotid) vs. untreated JCR). Likewise, hypertension in JCR animals was significantly attenuated by intra‐abdominal lipectomy (MABP=156±3 mmHg JCR vs. 90±6 mmHg SD vs. 132±4 mmHg JCR+lipectomy). 20‐hydroxyeicosatetraeonic acid (20‐HETE), an arachidonic acid metabolite known to be a potent vasoconstrictor in resistance arteries, was significantly elevated in the visceral adipose tissue of JCR rats (~6 fold vs. SD). Like intra‐abdominal lipectomy, 20‐HETE antagonists restored large artery elasticity, blocked MMP12 activation and elastin degradation and significantly decreased blood pressure (125±3 mmHg JCR+20‐HETE antagonists) in JCR rats. Thus, 20‐HETE may be an important adipokine that mediates, in part, the adverse effects of expanded visceral fat volume in the metabolic syndrome. Its removal and inhibition may provide therapeutic and pharmacological approaches, respectively, for the management of central obesity‐driven large artery stiffness and hypertension in the metabolic syndrome.Support or Funding InformationNational Heart, Lung and Blood Institute (NHLBI): 1F31HL137356‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract 122: 20-HETE Antagonists Normalize Large Artery Stiffness and Systolic Blood Pressure in Metabolic Syndrome

Large artery stiffness is a causal factor in development of systolic hypertension. 20-hydroxyeicosatetraeonic acid (20-HETE), a cytochrome CYP450-derived arachidonic acid metabolite, is known to be elevated in resistance arteries in hypertensive animal models and in obesity in humans, but the role of 20-HETE in regulation of large artery remodeling in metabolic syndrome has not been investigated. Unlike normal (Sprague-Dawley (SD)) rats, large arteries (aorta, carotid and &gt;100μM mesenteric arteries) of metabolic syndrome rats (JCR:LA-cp, JCR) express CYP4A and 4F, CYP450s which make 20-HETE in rats (2-fold increase vs. SD). Consequently, 20-HETE production is elevated in large arteries of JCR rats. We hypothesized that this elevated 20-HETE increases matrix metalloproteinase 12 (MMP12, an elastase) activation leading to increased degradation of elastin, increased large artery stiffness and increased systolic blood pressure. A 3-4 fold increase in 20-HETE production in large arteries of JCR vs. SD rats correlated with increased elastin degradation (3-6 fold) and increased arterial stiffness (~75%). 20-HETE antagonists blocked elastin degradation in JCR rats concomitant with blocking MMP12 activation. Importantly, 20-HETE antagonists and MMP12 inhibition (pharmacological and MMP12-shRNA-Lnv) significantly decreased (~60% vs. untreated JCR) large artery stiffness in JCR rats. 20-HETE antagonists also decreased systolic (182±3 mmHg JCR, 145±3 mmHg JCR+20-HETE antagonists) but not diastolic (125±4 mmHg JCR, 124±4 mmHg JCR+20-HETE antagonists) blood pressure in JCR rats. Whereas diastolic pressure was fully angiotensin II (Ang II)-dependent, systolic pressure was only partially Ang II-dependent, and large artery stiffness in JCR rats was Ang II-independent. These results suggest that 20-HETE-dependent regulation of systolic blood pressure may be a unique feature of metabolic syndrome related to high CYP4A/4F expression and resultant high 20-HETE production in large conduit arterial stiffness, which is a primary determinant of systolic blood pressure. These findings may have implications for management of systolic hypertension in patients with metabolic syndrome.

Ambulatory blood pressure response to a bout of HIIT in metabolic syndrome patients.

The effectiveness of exercise to lower blood pressure may depend on the type and intensity of exercise. We study the short-term (i.e., 14-h) effects of a bout of high-intensity aerobic interval training (HIIT) on blood pressure in metabolic syndrome (MetS) patients. Nineteen MetS patients (55.2±7.3years, 6 women) entered the study. Eight of them were normotensive and eleven hypertensive according to MetS threshold (≥130mmHg for SBP and/or ≥85mmHg for DBP). In the morning of 3 separated days, they underwent a cycling exercise bout of HIIT (>90% of maximal heart rate, ~85% VO2max), or a bout of isocaloric moderate-intensity continuous training (MICT; ~70% of maximal heart rate, ~60% VO2max), or a control no-exercise trial (REST). After exercise, ambulatory blood pressure (ABP; 14h) was monitored, while subjects continued their habitual daily activities wearing a wrist-band activity monitor. No ABP differences were found for normotensive subjects. In hypertensive subjects, systolic ABP was reduced by 6.1±2.2mmHg after HIIT compared to MICT and REST (130.8±3.9 vs. 137.4±5.1 and 136.4±3.8mmHg, respectively; p<0.05). However, diastolic ABP was similar in all three trials (77.2±2.6 vs. 78.0±2.6 and 78.9±2.8mmHg, respectively). Motion analysis revealed no differences among trials during the 14-h. This study suggests that the blood pressure reducing effect of a bout of exercise is influence by the intensity of exercise. A HIIT exercise bout is superior to an equivalent bout of continuous exercise when used as a non-pharmacological aid in the treatment of hypertension in MetS.

GW27-e0570 The predictive risk factors of silent ischemic stroke event is nocturnal blood pressure and central aortic systolic blood pressure in Metabolic Syndrome

GW27-e0570 The predictive risk factors of silent ischemic stroke event is nocturnal blood pressure and central aortic systolic blood pressure in Metabolic Syndrome

20‐HETE Increases Large Artery Stiffness and Systolic Blood Pressure in Metabolic Syndrome

Hypertension is a risk factor that is associated with the metabolic syndrome. Large artery stiffness, which is in part a result of elastin degradation, plays a causal role in the development of isolated systolic hypertension, which is especially common in the elderly. Levels of 20‐hydroxyeicosatetraeonic acid (20‐HETE), a cytochrome (CYP)‐derived arachidonic acid metabolite, are greatly elevated in hypertensive animal models and loosely associated with obesity in humans, but 20‐HETE's role in the regulation of arterial stiffness in the metabolic syndrome has not been investigated. We hypothesized that elevated 20‐HETE in metabolic syndrome increases matrix metalloproteinase 12 (MMP12) activation leading to increased elastin degradation, increased large artery stiffness and increased systolic blood pressure. Our study shows that elastin degradation was increased ~4 fold in large arteries of metabolic syndrome rats (JCR:LA‐cp, JCR) vs. Sprague‐Dawley (SD) control rats. This correlated with increased large artery stiffness (75%±2% JCR vs. SD). 20‐SOLA (2,5,8,11,14,17‐hexaoxanonadecan‐19‐yl 20‐hydroxyicosa‐6(Z),15(Z)‐dienoate) a 20‐HETE antagonist, blocked elastin degradation in JCR rats, concomitant with decreasing MMP12 activation. Importantly, both 20‐SOLA and MMP12 inhibition (pharmacological and MMP12‐shRNA‐Lnv) decreased large artery stiffness in JCR rats (3%±2% JCR+20‐SOLA vs. SD, 18%±4.3% JCR+MMP12 inhibition vs. SD). 20‐SOLA and MMP12 inhibition also decreased systolic but not diastolic blood pressure in JCR rats (113±6 mmHg SD, 159±4 mmHg JCR, 130±4 mmHg JCR+20‐SOLA, 139±5 JCR+MMP12 mmHg inhibition). These data suggest that a portion of the systolic but not diastolic component of hypertension in the metabolic syndrome JCR rats is 20‐HETE‐sensitive and dependent on large artery stiffness/compliance. The source(s) of 20‐HETE and MMP12 responsible for increased elastin degradation and large artery stiffness are likewise unknown. Intra‐abdominal lipectomy (removal of visceral fat=5% body weight) in JCR rats decreased MMP12 activation, elastin degradation and large artery stiffness to levels achieved with 20‐SOLA and observed in SD control rats, suggesting: 1) that this 20‐HETE is largely derived from visceral (intra‐abdominal) adipose tissue, and 2) that MMP12 involved in the regulation of vascular stiffness is also derived primarily from visceral adipose tissue. Future implications of these findings may be important for systolic hypertension management through 20‐HETE and/or MMP12 inhibition.Support or Funding InformationSupported by NIH R01HL093052.

Individual nutritional counseling with monitoring home blood pressure improve anthropometric factors and home blood pressure in metabolic syndrome

Individual nutritional counseling with monitoring home blood pressure improve anthropometric factors and home blood pressure in metabolic syndrome

Effects of Lesions to Capsaicin-Sensitive Nerves on Blood Pressure in Metabolic Syndrome in Rats

The effects of lesions to capsaicin-sensitive nerves (capsaicin, 150 mg/kg, s.c.) on arterial blood pressure (BP) were studied in rats with metabolic syndrome induced by fructose (12.5% solution as drinking water, 10 weeks); plasma glucose, triglycerides, and lipid peroxidation products were also measured in these animals. Systolic BP was measured using a noninvasive method (Coda, Kent Scientific, USA). The fructose diet induced impairment to glucose tolerance, arterial hypertension, and increases in the levels of triglycerides and peroxidation products. Fructose consumption by animals previously given capsaicin (deafferentation of capsaicin-sensitive nerves) was not accompanied by abnormalities in glucose tolerance or increases in BP or triglyceride concentrations. Deafferentation did not alter the increase in peroxidation product levels in fructose-consuming rats. These studies lead to the conclusion that capsaicin-sensitive nerves are involved in the mechanisms of development of insulin resistance and arterial hypertension in metabolic syndrome.

Relationship between obstructive sleep apnea and markers of cardiovascular alterations in never-treated hypertensive patients

We addressed a question if there is a relationship between severity of newly diagnosed obstructive sleep apnea (OSA) and markers of cardiovascular alterations in middle-aged untreated hypertensive patients. In 121 consecutive patients with never-treated essential hypertension (mean age 35.9±10.1 years; 97 men and 24 women) evaluation of office and ambulatory blood pressure (BP) measurements, metabolic syndrome (MS) components and markers of alterations in cardiovascular system including left ventricular structure and function, carotid artery wall intima-media thickness (cIMT) and urinary albumin excretion (UAE) was performed. OSA was classified as mild (apnea/hypopnea index (AHI) 5-15 events h(-1)) or moderate-to-severe (AHI >15 events h(-1)). Mild and moderate-to-severe OSA were diagnosed in 30% and 20% of patients, respectively. No differences in nighttime BP levels and decline between patients with and without OSA were observed. The patients with moderate-to-severe OSA were characterized by higher cIMT (0.74±0.16 vs. 0.60±0.15 mm; P=0.001), UAE (14.5±6.9 vs. 10.0±8.0 mg 24 h(-1); P=0.014), relative wall thickness (0.42±0.05 vs. 0.39±0.05; P=0.023) and by a higher degree of diastolic dysfunction (E'-wave velocity 11.4±3.2 vs. 15.5±3.8 m s(-1); P<0.001) as compared with the patients without OSA. In multivariate analysis, AHI independently of BP and MS components correlated with UAE, relative wall thickness and E'-wave velocity. In the middle-aged never-treated hypertensive patients, moderate-to-severe OSA correlates with markers of cardiovascular alterations independently of BP levels and MS components.

Effects of an isocaloric healthy Nordic diet on ambulatory blood pressure in metabolic syndrome: a randomized SYSDIET sub-study

Dietary pattern is central in the prevention of hypertension and blood pressure (BP)-related diseases. A diet based on healthy Nordic foods may have a favourable impact on BP. The objective was to clarify whether a Nordic alternative for a healthy food pattern would have beneficial effects on ambulatory BP in subjects with metabolic syndrome (MetS). In total, 37 subjects were randomized to either a healthy Nordic diet or a control diet. A healthy Nordic diet embraced whole grains, rapeseed oil, berries, fruits, vegetables, fish, nuts and low-fat dairy products of Nordic origin. The mean nutrient intake in the Nordic countries formed the control diet, embracing wheat products, dairy fat-based spread and a lower intake of fruits, vegetables and fish. Diets were isoenergetic. Ambulatory BP was monitored and 24-h urine was collected before and after 12 weeks of intervention. After 12 weeks, ambulatory diastolic BP (-4.4 mm Hg; P=0.001) and mean arterial pressure (-4.2 mm Hg; P=0.006) were lowered by the healthy Nordic diet compared with the control diet, whereas changes in ambulatory systolic BP did not differ significantly between diets (-3.5 mm Hg; P=0.122). Heart rate tended to be lower in those on the healthy Nordic diet (P=0.057). Urinary sodium and potassium excretions were unaffected by diets and consequently not associated with the healthy Nordic diet-induced lowering of BP. Consumption of Nordic varieties of health-enhancing foods for 12 weeks decreased diastolic ambulatory BP and mean arterial pressure in subjects with features of MetS during weight-stable condition, suggesting beneficial effects of a healthy Nordic dietary pattern on ambulatory BP.

Assessing clustering of metabolic syndrome components available at primary care for Bantu Africans using factor analysis in the general population

BackgroundTo provide a step-by-step description of the application of factor analysis and interpretation of the results based on anthropometric parameters(body mass index or BMI and waist circumferenceor WC), blood pressure(BP), lipid-lipoprotein(triglycerides and HDL-C) and glucose among Bantu Africans with different numbers and cutoffs of components of metabolic syndrome(MS).MethodsThis study was a cross-sectional, comparative, and correlational survey conducted between January and April 2005, in Kinshasa Hinterland, DRC. The clustering of cardiovascular risk factors was defined in all, MS group according to IDF(WC, BP, triglycerides, HDL-C, glucose), absence and presence of cardiometabolic risk(CDM) group(BMI,WC, BP, fasting glucose, and post-load glucose).ResultsOut of 977 participants, 17.4%( n = 170), 11%( n = 107), and 7.7%(n = 75) had type 2 diabetes mellitus(T2DM), MS, and CDM, respectively. Gender did not influence on all variables. Except BMI, levels of the rest variables were significantly higher in presence of T2DM than non-diabetics. There was a negative correlation between glucose types and BP in absence of CDM. In factor analysis for all, BP(factor 1) and triglycerides-HDL(factor 2) explained 55.4% of the total variance. In factor analysis for MS group, triglycerides-HDL-C(factor 1), BP(factor 2), and abdominal obesity-dysglycemia(factor 3) explained 75.1% of the total variance. In absence of CDM, glucose (factor 1) and obesity(factor 2) explained 48.1% of the total variance. In presence of CDM, 3 factors (factor 1 = glucose, factor 2 = BP, and factor 3 = obesity) explained 73.4% of the total variance.ConclusionThe MS pathogenesis may be more glucose-centered than abdominal obesity-centered in not considering lipid-lipoprotein , while BP and triglycerides-HDL-C could be the most strong predictors of MS in the general population. It should be specifically defined by ethnic cut-offs of waist circumference among Bantu Africans.

Soybean or Fish Oil Increases Adiponectin and Nitric Oxide Levels and Decreases Blood Pressure in Metabolic Syndrome

Sixty five women (mean age 47,9 ± 9,98 y) were studied in a 90 days parallel randomized design. A control group maintained their usual diet; the second group received 29 g/day of soy bean (kinako); the third group received 3 g/day of fish oil n‐3 fatty acids; and the fourth group received fish oil (3 g/day) and kinako (29 g/day). Anthropometric, blood pressure, inflammatory markers, anti‐inflammatory marker (adiponectin) and nitric oxide (NO) concentrations were evaluated. In relation to the baseline values, the group that received fish oil and kinako concomitantly presented statistically significant decrease in systolic blood pressure (p&lt;0,05), whereas there was a significant decrease in diastolic blood pressure (DBP) in the control group (p&lt;0,05), kinako group (p&lt;0,01), and fish oil group (p&lt;0,01) after 90 days, There was a significant increase in adiponectin (p&lt;0,01) and NO values (p&lt;0,05) after 90 days in the kinako and fish oil groups. Differences between treatment groups verified a significant decrease (p&lt;0.05) in DBP in kinako group after 90 days when compared to the results obtained from fish oil and kinako group. In conclusion, the findings of increased serum adiponectin and NO metabolite levels after 90 days both in fish oil and soy groups reinforce the importance of the influence of adiponectin and NO levels on blood pressure decrease in patients with MetS.

Oral Administration of Bis(aspirinato)zinc(II) Complex Ameliorates Hyperglycemia and Metabolic Syndrome-Like Disorders in Spontaneously Diabetic KK-Ay Mice: Structure-Activity Relationship on Zinc-Salicylate Complexes

In recent years, the number of patients suffering from diseases, such as cancer, apoplexy, osteoporosis, hypertension, and type 2 diabetes mellitus is increasing worldwide. Type 2 diabetes, a lifestyle-related disease, is recognized as a serious disease. Various types of pharmaceutics for diabetes have been used. Since the relationship between diabetes and biometals such as vanadium, copper, and zinc ions has been recognized for many years, we have been developing the anti-diabetic metal complexes as new candidates. We found that several zinc(II) (Zn) complexes exhibit glucose-lowering activity for treating type 2 diabetes. High doses of salicylates have been known to reverse hyperglycemia and hyperinsulinemia in type 2 diabetic patients. These findings strongly suggest that the combined use of Zn and salicylates achieves the synergism in treating type 2 diabetes. Because aspirin, acetyl salicylic acid, has a chelating ability, we used it as a ligand to Zn. Several Zn-salicylate complexes were prepared and their biological activities were examined in this study. The complexes with an electron-withdrawing group in the ligand exhibited higher in vitro insulinomimetic activity than those of Zn complexes with an electron-donating group in the ligand. When bis(aspirinato)Zn (Zn(asp)₂) complex was orally administered on KK-A(y) mice with hereditary type 2 diabetes, the diabetic state was improved. In addition, this complex exhibited normalizing effects on serum adiponectin level and high blood pressure in metabolic syndrome. In conclusion, Zn(asp)₂ complex is newly proposed as a potent anti-diabetic and anti-metabolic syndrome agent.

Association of Metabolic Syndrome and Blood Pressure Nondipping Profile in Untreated Hypertension

There is a marked association between metabolic syndrome (MS) and increased cardiovascular risk. Moreover, nondipping (patients with <10% decline in the asleep relative to the awake blood pressure (BP) mean) has also been associated with increased cardiovascular morbidity and mortality. We investigated the association between MS and impaired nocturnal BP decline in 1,770 nondiabetic, untreated hypertensive patients (824 men and 946 women), 48.7 +/- 13.2 years of age. BP was measured by ambulatory monitoring for 48 h to increase reproducibility of the dipping pattern. Physical activity was simultaneously monitored every minute by wrist actigraphy. MS was present in 42.4% of the patients. The prevalence of a nondipper BP profile was significantly higher in patients with MS (46.1% vs. 37.5% in patients without MS, P < 0.001). Patients with MS were characterized by significant elevations in uric acid (5.9 mg/dl vs. 5.2 mg/dl, P < 0.001), fibrinogen (314 mg/dl vs. 304 mg/dl, P = 0.021), and globular sedimentation rate (13.8 mm vs. 11.6 mm, P < 0.001). Nondipping was significantly associated to the presence of MS in a multiple logistic regression model adjusted by other significant confounding factors, including age, serum creatinine, and cigarette smoking. The single most relevant factor in the definition of MS associated to nondipping was elevated waist perimeter. This study documents a significant increase of a blunted nocturnal BP decline in patients with MS. Patients with MS were also characterized by elevated values of relevant markers of cardiovascular risk, including fibrinogen and globular sedimentation rate.

Quantitative trait loci associated with blood pressure of metabolic syndrome in the progeny of NZO/HILtJ × C3H/HeJ intercrosses

In a previous study in 15 inbred mouse strains, we found highest and lowest systolic blood pressures in NZO/HILtJ mice (metabolic syndrome) and C3H/HeJ mice (common lean strain), respectively. To identify the loci involved in hypertension in metabolic syndrome, we performed quantitative trait locus (QTL) analysis for blood pressure with direction of cross as a covariate in segregating F2 males derived from NZO/HILtJ and C3H/HeJ mice. We detected three suggestive main-effect QTLs affecting systolic and diastolic blood pressures (SBP and DBP). We analyzed the first principle component (PC1) generated from SBP and DBP to investigate blood pressure. In addition to all the suggestive QTLs (Chrs 1, 3, and 8) in SBP and DBP, one suggestive QTL on Chr 4 was found in PC1 in the main scan. Simultaneous search identified two significant epistatic locus pairs (Chrs 1 and 4, Chrs 4 and 8) for PC1. Multiple regression analysis revealed three blood pressure QTLs (Bpq10, 100 cM on Chr 1; Bpq11, 6 cM on Chr 4; Bpq12, 29 cM on Chr 8) accounting for 29.4% of blood pressure variance. These were epistatic interaction QTLs constructing a small network centered on Chr 4, suggesting the importance of genetic interaction for development of hypertension. The blood pressure QTLs on Chrs 1, 4, and 8 were detected repeatedly in multiple studies using common inbred nonobese mouse strains, implying substantial QTL independent of development of obesity and insulin resistance. These results enhance our understanding of complicated genetic factors of hypertension in metabolic diseases.