Accumulating evidence suggests that volume overload in drug-resistant hypertension (RH) may contribute to the high prevalence of obstructive sleep apnea-hypopnea (OSAH). Upon recumbency, leg fluid volume moves rostrally causing an increase in nuchal and peripharyngeal fluid content, subsequently obstructing airflow. Rostral fluid displacement following lower body positive pressure (LBPP) application and occurring spontaneously overnight were evaluated in subjects with RH (n = 25) and controlled hypertension (n = 15). In both groups, the reduction in mean upper airway cross-sectional area with LBPP strongly related to the amount of fluid displaced from the legs (R2 = 0.41; p<0.0001), although its magnitude was greater in the RH group (p=0.001; adjusted for propensity score). In both groups, the apnea-hypopnea index strongly related to the amount of fluid spontaneously displaced from the legs during sleep (R2 = 0.56; p<0.0001), although its magnitude was greater in the RH group (p=0.01; adjusted for propensity score).

Background: Hypertension is synonymous with high blood pressure, where blood exerts a great force on the arterial walls. Smoking cigarettes is known to cause negative health outcomes, specifically increase blood pressure. Adversely, physical activity is known to provide many health benefits, including the reduction of blood pressure. This study examines the impact of physical activity on the association between smoking and hypertension. Methods: Using secondary data from National Health and Nutrition Examination Survey (NHANES) 2007-2008, demographics of the population were described via descriptive statistics. Regressions were run using different models, controlling for various variables (age, ethnicity, sex, poverty to income ratio (PIR), body mass index (BMI), and interaction (smoking x physical activity)) to determine the association between smoking and hypertension. Odds ratios and 95% confidence intervals were used to determine statistical significance throughout all the analyses performed. Results: In total, 10,149 cases were included in the study analysis. 10.9% of the cases were smokers, 48.1% were physically activity, and 28.6% were hypertensive. OR’s for the various models observing smoking and hypertension were 1.48 (1.29, 1.69), 1.42 (1.22, 1.65), 1.37 (1.12, 1.67), and 1.36 (1.10, 1.68). In the final model which controlled for all variables including the interaction term, the OR was 1.12 (0.47, 2.67). Conclusions: Smokers had significantly higher rates of hypertension in all the models. The final model which observed smokers who were physical active found that the relationship between smoking and hypertension was no longer significant. This study suggests physical activity as a mode of intervention to reduce blood pressure in smokers.

HEALTH RISKS, NUTRITION ASSESSMENT AND DISEASE PREVALENCE AMONG AFRICAN IMMIGRANT GROUPS IN ATLANTA GEORGIA Background: Though past studies have suggested immigrants are generally healthier than the native population, the immigrant acquisition of chronic diseases, such as obesity, hypertension and diabetes, over time, is poorly understood among African immigrants. Objective: The objective of this study was to evaluate the health status, health risks chronic disease prevalence, and acculturation among immigrants from Ghana, Kenya and Nigeria. Participants/setting: 130 adult African immigrants living in Atlanta and attending any of four church health fairs. Participants completed anthropometric, health status assessments and a Home Environment Family connections Survey. Main outcome measures: BMI, waist circumference, blood glucose, blood pressure, fruit consumption frequency, availability of sugared sweetened drinks and physical activity were assessed and compared among African immigrant groups. Statistical analysis: Prevalence was calculated. Independent sample t-test, one-way ANOVA, and Pearson correlation coefficients were used to compare anthropometrics while demographic and categorical survey data was compared using chi-squared tests. Results: There was a statistically significant difference in the mean BMIs of African Immigrants (Nigeria and Ghana) (p=0.013) but not in the waist circumferences (p>0.05). High blood pressure prevalence in Ghanaian, Nigerian and Kenyan immigrants was 42.6 %, 36.8 %, and 25.8 % respectively. The prevalence of diabetes in Ghanaian, Nigeria and Kenyan immigrants was 18.8 %, 11.8 %, and 4.9 % respectively. Obesity prevalence in Nigerian, Kenyan and Ghanaian immigrants was 52.6 %, 45.8 %, and 31.1 % respectively. There were no statistically significant associations between the Years of Stay status and disease prevalence (p>0.05). There were no statistically significant associations between the BMI status and the availability of sugared sweetened drinks in the household, fruit consumption frequency, or the physical activity of African immigrants. Conclusion: African immigrants appear to have a slightly lower prevalence of diabetes, but a higher prevalence of hypertension and obesity than the United States population. Acculturation did not play a strong role in determining the health trajectories of African immigrants. Grouping immigrants by their country of origin does provide another important dimension in understanding the variation in immigrant health as each group had significant differences in the prevalence of diseases.

The work reported in this thesis is an investigation of certain aspects of both the blood pressure (BP) elevating properties and BP lowering properties of arginine vasopressin (AVP). The hypothesis that endothelin (ET) contributes to the exaggerated pressor responsiveness of the spontaneously hypertensive rat (SHR) to AVP was tested by comparing the changes of BP, cardiac output (CO), and total peripheral conductance (TPC) to AVP in SHR to those in Wistar-Kyoto rats (WKY) both in the presence and absence of bosentan, a non-selective ET antagonist. Bosentan antagonized the BP responses to exogenous ET-1 in a competitive fashion. The pressor effects of AVP and Ang II were exaggerated in the SHR compared to WKY. Except for the highest dose of AVP, pre-treatment with bosentan blunted the increases in BP and the decreases in total peripheral conductance (TPC) evoked by AVP in the SHR, but not in the WKY. In contrast to AVP, bosentan blunted the increases in BP evoked by lower doses of Ang II in both strains, although the effect was more pronounced in the SHR. These results suggest that ET contributes to the hemodynamic effects of AVP in the SHR and to the effects of Ang II in both strains. The findings support the hypothesis that ET contributes to the exaggerated pressor responsiveness of SHR to AVP. Cessation of a 3 hour infusion of AVP (20 ng/kg/min) results in a dramatic and prolonged decrease in BP below pre-infusion basal levels in hypertensive rats, but not in normotensive control rats. This phenomenon has been termed the "withdrawal-induced antihypertensive phenomenon" (WAP). In order to determine the time course of the WAP, and the role of CO and TPC in the WAP, BP was recorded by radiotelemetry and CO was recorded from aonic flowprobes in conscious unrestrained rats before, during, and after a 3 hr i.v. infusion of 20 ng/kg/min of AVP. Baseline mean arterial BP values were lower, and the magnitude of the WAP was less in SHR when BP was recorded with radiotelemetric implants than in another group in which BP was recorded with conventional externalized femoral arterial catheters. Strikingly, absolute BP values recorded both during and after the AVP infusion were similar in the two groups. BP remained decreased for several days in SHR infused with AVP with complete recovery requiring 6-7 days. In rats instrumented with aortic flow probes, the fall in pressure following cessation of the AVP infusion was associated with a large decrease in CO below control levels in the SHR. The time-course of the CO responses approximated the time-course of the pressure responses. These results lead to the following conclusions: firstly, telemetry is a superior method for recording BP in hypertensive animals, and the lower magnitude of the WAP was probably related to the lower basal BPs recorded by this method; secondly, the mechanism accounting for the WAP must be of a long duration; thirdly, the WAP is mediated by a fall in CO and not by an increase in TPC. In conclusion, the results of the thesis support the hypothesis that ET contributes to the BP elevating properties of AVP and, consequently, the exaggerated pressor responsiveness of SHR to the peptide, and that the BP lowering properties of AVP are mediated by a fall in CO.

Methylglyoxal (MG), a metabolite of glucose, causes non-enzymatic glycation of proteins to form irreversible advanced glycation end products (AGEs). Increased MG production, which in turn gives rise to AGEs, has been linked to the development of complications in diabetes. However, the role of MG and AGEs in hypertension has not been investigated widely. The previous study from our laboratory showed that the cellular levels of MG and MG-induced AGE formation are significantly higher in cultured aortic smooth muscle cells from spontaneously hypertensive rats (SHR) than those from normotensive Wistar-Kyoto rats (WKY). Using immunofluorescence staining with specific monoclonal antibodies against MG-induced AGEs, the present studies show a strong association of MG and its AGE products (Nå-carboxyethyl-lysine and Nå-carboxymethyl-lysine) with hypertension in SHR. The blood pressure of SHR was not different from that of WKY rats at 5 wks of age. From 8 wks onwards, blood pressure was significantly elevated compared to age-matched WKY rats. Importantly, this increase in blood pressure coincided with an elevated MG level in plasma and aorta of SHR in an age-dependent fashion compared to age-matched WKY rats, although no difference was observed in blood glucose levels between these two strains. Our data showed an increased MG level in plasma and aorta, but not in kidney or heart, in SHR at an early age of 8 wks, suggesting, in addition to diabetes/hyperglycemic or hyperlipidemic conditions, the accumulation of MG in blood vessel walls plays an important role in the development of hypertension or its complications even in the absence of diabetes. Moreover, we observed increased blood pressure and vascular remodeling in Sprague Dawley rats which had been treated to increase endogenous MG and related AGEs. After inhibiting MG and MG-induced AGE generation in SHR, hypertension development in this genetic hypertension model was delayed and vascular remodeling was reversed. Our data indicate that increased MG and AGE formation may play an important role in the development of hypertension.

Several studies have found a positive correlation between hypertension and hyperhomocysteinemia. Increasing evidence implicates oxidative stress as one of the initiating events closely linked to the homocysteines ability to damage endothelium, subsequently causing vascular dysfunction. We previously found that heparin protects cultured endothelial cells from free radical injury and oral heparin at 1 mg/kg/48h prevents venous thrombosis in a rat model in vivo. Our objective was to study the protective effects of oral heparin in a rat model with elevated plasma homocysteine (Hcy) concentrations, and begin to elucidate whether the pathophysiological effects of Hcy are mediated through an oxidative mechanism causing endothelial dysfunction.<p> Elevated plasma Hcy levels were induced by feeding male Wistar Kyoto rats a diet containing an additional 1.7% methionine for 8 weeks. Groups included rats fed additional methionine, methionine plus oral heparin (1 mg/kg/48h by gastric feeding tube), and age-matched controls fed normal rat chow. At the end of 8 weeks of treatment, rats were anesthetized using 1.5% isoflurane in 100% oxygen. Hemodynamics parameters were assessed by inserting a Millar Mikro Tip pressure transducer into the left ventricular chamber and the thoracic aorta. Fasting plasma total Hcy levels were measured using a Hcy immunoassay kit with an Abbott IMx instrument. Malondialdehyde (MDA) concentrations, a lipid peroxidation product and marker for oxidative stress, was measured by a spectrophotometric method in serum and tissue samples. Glutathione (GSH) concentrations, an important antioxidant for low-level oxidative stress was measured by HPLC in plasma and tissues samples. Lastly, tissue samples from each experimental group were stained with the TUNEL method to assess their respective percentage of apoptotic endothelial cells. Results were expressed as mean ± S.E. Unpaired Students two-tailed t-test was employed to assess the difference between groups with p < 0.05 considered significant.<p> Plasma Hcy was significantly elevated after 8 weeks in the methionine (7.17 ± 0.46 umol/L) and methionine plus heparin treated rats (7.02 ± 0.40 umol/L) compared to control (5.46 ± 0.36 umol/L). All measures of arterial pressure, systolic (SP) and diastolic pressure (DP) and mean arterial pressure (MAP), were significantly elevated in rats fed the methionine diet without heparin (119.9 ± 3.9 mmHg; 90.3 ± 3.5 mmHg; 97.7 ± 2.9 mmHg, respectively) compared to controls (107.8 ± 2.5 mmHg; 79.2 ± 2.1 mmHg; 88.8 ± 2.2 mmHg, respectively) but not compared to heparin (114.7 ± 3.3 mmHg; 83.4 ± 2.4 mmHg; 93.8 ± 2.7 mmHg, respectively). Left ventricular end diastolic pressure (LVEDP) was significantly elevated with the methionine diet without heparin (14.2 ± 2.5 mmHg) but not with heparin treatment (8.4 ± 1.9 mmHg) versus controls (7.1 ± 1.1 mmHg). Also, left ventricular systolic pressure (LVSP) was significantly elevated in the methionine fed rats after 8 weeks (122.6 ± 3.2 mmHg) compared to controls (112.3. ± 2.9 mmHg). Heparin treatment had no effect on LVSP (119.9 ± 3.2 mmHg). <p> Additionally, the results of this study showed that oral heparin treatment significantly decreased liver MDA concentrations (2.42 ± 0.28 nmol/mg protein) compared to the methionine treated group (5.10 ± 0.96 nmol/mg protein) and methionine treatment alone significantly reduced MDA concentrations in kidney tissue (1.59 ± 0.12 nmol/mg protein) compared with controls (3.26 ± 0.66 nmol/mg protein). Methionine diet significantly decreased GSH concentrations in plasma (0.59 ± 0.59 µmol/L) compared with controls (4.24 ± 0.94 µmol/L) and oral heparin treatment significantly attenuated the decrease in GSH concentrations in left ventricle tissue samples (0.0229 ± 0.0023 µmol/mg protein) compared with methionine treatment alone (0.0135 ± 0.0016 µmol/mg protein). <p> Elevated plasma homocysteine levels, induced by methionine diet feeding significantly increased the percent of apoptotic endothelial cells in the aortas (17.04 ± 3.74%) and superior mesenteric arteries (17.99 ± 1.90%) of WKY rats compared with control aortas and mesenteric arteries (6.08 ± 3.24%; 7.43 ±1.62%, respectively) and compared to oral heparin treated mesenteric arteries (7.31 ± 1.18%). <p> The results of this study showed that elevated plasma levels of Hcy correlate with the development of hypertension, defined as significantly increased arterial pressure. Oral heparin treatment prevented the significant increase in arterial pressures and LVEDP, decreased MDA concentrations and therefore the oxidative stress on the liver, attenuated the decrease caused by elevated plasma Hcy in left ventricle GSH concentrations, and significantly reduced the number of apoptotic endothelial cells in the superior mesenteric artery of high methionine fed rats. We conclude that elevated levels of plasma Hcy contributes to the development of hypertension and furthermore towards the onset of heart failure likely through an oxidative mechanism and that oral heparin reduces the overall oxidative stress in specific physiological environments, preventing Hcy mediated endothelial cell apoptosis.

Persistent hypertension is associated with a greater incidence of organ damage and conditions such as stroke, heart failure and endstage kidney disease, which results in increased cardiovascular (CV) morbidity and mortality. Among the patients receiving antihypertensive treatment, the level of adequate blood pressure (BP) control (<140/90 mm Hg) is only 30%-50%. These antihypertensive drugs reduce the risk of CV events only by 20% and stroke by 40%, besides causing adverse effects. The spontaneously hypertensive stroke-prone rat (SHRsp) is a good model of essential hypertension. It starts developing hypertension at 5-6 weeks of age which becomes established hypertension at 12-16 weeks. The SHRsp also develops oxidative stress (characterized by low glutathione levels) and inflammation. We have previously shown that consumption of broccoli sprouts (BSp) decreased oxidative stress, inflammation and blood pressure in both male and female SHRsp. BSp contain sulforaphane glucosinolate (SGS), the precursor of the phase 2 protein inducer sulforaphane. BSp low in SGS did not have these effects. Furthermore, BSp did not have any measurable effects on the normal physiology of Sprague Dawley (SD) rats. The objectives of this study were to determine: (1) the importance of a food matrix in causing these beneficial effects, i.e., can one get the same effects by administration of sulforaphane alone?, (2) whether dietary sulforaphane decreases the level of nitrosylated proteins in the kidneys of SHRsp, (3) whether dietary sulforaphane increases the phase 2 enzyme ã-glutamyl-L-cysteine ligase expression (ã-GCS ), (4) whether dietary sulforaphane increases the phase 2 enzyme glutathione reductase (GRed) expression, (5) whether dietary sulforaphane increases the phase 2 enzyme thioredoxin reductase (TrxR1) expression and (6) whether dietary sulforaphane protects renal artery structure. After 1 week of adaptation, the 4 week old female SHRsp and SD rats were divided into four groups and administered daily by gavage: (i) Corn oil (vehicle) alone (Control); (ii) sulforaphane (5 µmol/kg body weight) in corn oil; (iii) sulforaphane (10 µmol/kg body weight) in corn oil; and (iv) sulforaphane (20 µmol/kg body weight) in corn oil. Systolic BP was determined weekly using a standard tail cuff noninvasive BP measurement system (model 29-SSP; Harvard Apparatus, St. Laurent, QC, Canada). The treatment lasted for 15 weeks. At the end of the treatment period, the animals were anesthetized with isoflurane (3%) and the BP was measured by the intra-arterial catheter method using a BP monitor (MK-2000 instrument; Muromachi Kikai Co., Ltd, Tokyo, Japan). Later, the animals were euthanized and perfused with normal saline, and tissues collected for histology, western blot, gene expression study or measurement of reduced glutathione (GSH). The results of the study showed that chronic administration of sulforaphane in SHRsp significantly increased phase 2 proteins (i.e., significantly increased kidney ã-GCS [0.93. ± 0.07 arbitrary unit (AU)] when compared with SHRsp control [0.36 ± 0.05(AU)] , decreased kidney nitrotyrosine (significantly lowered the levels of nitrotyrosine [0.917± 0.16 AU ] when compared with SHRsp control [1.37± 0.2 AU], protected the arterial structure of small resistance vessels in kidneys, and significantly attenuated the increase in blood pressure by 22-43 mm Hg by the end of the study. In conclusion, the results of this thesis demonstrate that: (i) A minimal change in our diet may have a major impact on our health, (ii) The beneficial health effects previously seen with consumption of BSp are due to the conversion of SGS to sulforaphane and (iii) Long term administration of sulforaphane in SHRsp attenuates the increase in BP and vascular alterations

Aim: The aim is to create a review that examines different forms of massage therapy and their effects on hypertension. Method: Literature review of 10 scientific articles on the subject of massage and its effects on blood pressure. The literature searches were made with PubMed and Cinahl using the keywords "massage therapy", "effects" and "blood pressure". Results: The articles showed that massage had a positive effect in lowering blood pressure. This could be explained by greater extent of relaxation in the participants investigated and an increased activity of parasympaticus and reduced secretion of stress hormones. The articles do not agree on what form of massage therapy is most effective in lowering blood pressure and it is uncertain for how long the effect can remain. Conclusion: Massage is usually seen as a treatment without scientific basis. There is evidence that suggests that massage therapy is an effective treatment for lowering blood pressure. The articles show that different forms of massage effect blood pressure in various ways. However, a larger randomized controlled trial is needed to determine whether massage therapy can be used as a complement to medical treatment for hypertension and what form of massage is the most effective.

The dissection of etiology of hypertension is a medical imperative. In the central nervous system, rostral ventral lateral medulla (RVLM) plays an essential role in the maintenance of arterial pressure and heart rate through tonic activation of the sympathetic vasomotor activity and regulation of baroreflex response. Oxidative stress of an enhanced cellular content of the reactive oxygen species, in particular the superoxide anion (O2-), has been implicated in hypertension. Superoxide dismutase (SOD) is one of the most important defense enzymes against the oxidative stress through catalysis of O2- into O2 and H2O2. SOD treatment has been demonstrated to decrease arterial pressure. Moreover, in addition to its peripheral vasodilatory effect, nitric oxide (NO) plays an active role in central regulation of arterial pressure and heart rate via modulation of the autonomic system. In the RVLM, both O2- and NO have been demonstrated to be involved in hypertension. Interactions between these two molecules, however, are not understood. The aims of this study are therefore to establish the significance of O2- and NO in the RVLM on blood pressure regulation in hypertension and to examine whether O2- interacts with NO to participate in the pathogenesis of hypertension. To examine their long term effects on mean systemic arterial pressure (MSAP) and heart rate (HR), SOD and/or NO was over-expressed by microinjection of the adenoviral vectors encoding the endothelial NO synthase (AdeNOS) and/or mitochondrial SOD (AdSOD2) into RVLM of the normotensive Wistar-Kyoto (WKY) rats or the spontaneously hypertensive rats (SHR). I found that microinjection of AdeNOS in the RVLM of SHR or WKY rats significantly decreased MSAP or HR that lasted for around 10 days postinjection. The hypotensive effect of AdeNOS was significantly greater in SHR than WKY rats. The AdeNOS-promoted hypotension in SHR, but not WKY rats, was followed by a rebound hypertension, detected in 28 days after the gene transfer. In the AdeSOD2-treated animals, I found a significant decrease in the MSAP in SHR, but not WKY rats, that lasted for about 7 days postinjection. On the other hand, no change in HR was detected in either SHR or WKY rats after the AdSOD2 gene transfer into the RVLM. In animals that received co-microinjection into the bilateral RVLM of AdeNOS and AdSOD2, there was a further prolonged decrease in MSAP or HR in SHR. The rebound hypertension observed in the AdeNOS-treated SHR was reversed to hypotension in the AdeNOS+AdSOD2-treated SHR. There was no difference in the hypotensive or bradycardiac effects in WKY rats that received the AdeNOS+AdSOD2 or AdeNOS gene transfer. Together these results suggest that (1) NO in RVLM plays an important role in central regulation of arterial pressure and heart rate under both normotensive and hypertensive conditions. A greater reduction in MSAP in the AdeNOS-treated SHR further indicates a reduced action of NO at the RVLM in the pathogenesis of hypertension. (2) An excessive oxidative stress of a reduced function of SOD2 in RVLM may be an important factor in neural mechanism of hypertension in SHR. The same mechanism, at the same time, may underlie the rebound hypertensive observed in the AdeNOS-treated SHR. (3) The excessive oxidative stress in the RVLM contributes to hypertension by at least two mechanisms. One is to cause oxidative injury in the RVLM and the other is to interact with NO to decrease already insufficient activity of NO in central cardiovascular regulation.

Insulin resistance was thought as the major etiology of hypertension of the metabolic syndrome. Both human and animal studies revealed sympathetic overactivity were present in the metabolic syndrome. Nowadays, most of the studies that examined the etiologies of hypertension of metabolic syndrome were focused on the pathophysiologic effects of insulin resistance on the peripheral vessels. However, there was no study ever examined the insulin resistance in cardiovascular regulatory centers of central nervous system or the pathogenesis of sympathetic overactivity in metabolic syndrome. Our previous study demonstrated that insulin plays a cardiovascular regulatory role in the nucleus tractus solitarii (NTS), one of the cardiovascular regulatory centers in the brain stem. We also demonstrated that the cardiovascular regulatory effects of insulin in the NTS were accomplished through activating PI3K-PKB/Akt-NO signaling pathways. Recently, increases in oxidative stress could raise the incidence rate of diabetes mellitus and cardiovascular diseases had been reported. Besides, it has been reported that there were marked increases in reactive oxidative species (ROS) in various hypertension animal models. It was also reported that elevation of ROS in various tissues may activate the mitogen-activated protein kinase (MAPK) superfamily. Activated MAPKs may phosphorylate insulin receptor substrate 1 (IRS1) on the serine 307 residue. It has been reported that IRS1S307 phosphorylation would inhibit normal insulin signal transduction. The aims of this thesis were to investigate whether the neuronal cells in the NTS would develop insulin resistance in the metabolic syndrome rats, whether development of insulin resistance in the NTS cause hypertension in the metabolic syndrome rats, which signaling molecule in insulin signaling pathway is the key molecule that cause insulin resistance in the NTS, and what the pathogenesis of insulin resistance is in the NTS of metabolic syndrome rats. In the pioneer study, Wistar-Kyoto (WKY) rats were fed with 10% fructose water as their drinking water for 8 weeks. Another group of fructose-fed WKY rats were fed with insulin sensitizer, rosiglitazone, since the 5th week. Blood pressure was measured by tail vein sphygmomanometer every week and venous blood were draw to measure blood sugar and insulin level every other week. Thereafter, all the rats enrolled in this study were fed with 10% fructose water with/without rosiglitazone for 2-3 weeks. My results demonstrated the blood pressure of fructose-fed WKY rats was significantly elevated after 2-week fructose feeding. But at the same time, HOMA-IR did not elevated, which indicated the insulin resistance in the peripheral did not develop yet. Interestingly, at the same time, endogenous insulin in the NTS was significantly elevated in the fructose-fed group. The cardiovascular responses of insulin in the NTS were diminished in the fructose-fed group. While in the rosiglitazone-treated group, the blood pressure and endogenous insulin in the NTS were decreased the baseline level. The cardiovascular responses of insulin in the NTS were restored in the rosiglitazone-treated group. These results indicated insulin resistance do develop in the NTS of fructose-fed rats, and the neuronal insulin resistance in the NTS can induce hypertension. The immunoblotting results demonstrated the phosphorylation of IRS1S307 was significantly elevated in the fructose-fed rats. While the phosphorylation of its downstream molecules, such as AktS473 and eNOSS1177, were significantly decreased as compared with the control group. In the NTS of rosiglitazone-treated group, the phosphorylation of IRS1S307 was decreased, and the phosphorylation of AktS473 and eNOSS1177 were restored. These results indicated that the underline pathogenesis of insulin resistance in the NTS was phosphorylation on the inhibitory serine residue of IRS1, which interfered with the normal insulin signal transduction in the NTS. Increases in ROS in the NTS of fructose-fed rats were demonstrated in the DHE histostaining. Phosphorylation of p38MAPK in the NTS of fructose-fed rats was also detected by immunoblotting. In the NTS of Tempol-treated fructose-fed rats, the phosphorylation of p38MAPK reduced and the nitric oxide production elevated to the basal level. Blood pressure decreased significantly when p38MAPK inhibitor, SB203680, was microinjected into the NTS of fructose-fed rats. These results indicated the pathogenesis of insulin resistance in the NTS is increases in ROS in the NTS, which activate p38MAPK and then phosphorylate IRS1S307. In conclusion, the neuronal cells in the NTS may develop insulin resistance in fructose-fed rats, and the neuronal insulin resistance in the NTS contributes to the hypertension of metabolic syndrome. The mechanism of insulin resistance in the NTS is phosphorylation on the serine 307 residue of IRS1, which interfere with insulin signaling and subsequent NO production in the NTS. The pathogenesis of IRS1S307 phosphorylation is activated p38MAPK which in turn is activated by ROS in the NTS.