Background: The incidence of Hypertensive Disorders in Pregnancy (HDP) is increasing in the US and is linked to serious long and short-term health problems for both mother and fetus. Vitamin D has been shown to have direct influence on molecular pathways involved in pregnancy. However a link between vitamin D status and HDP in Pregnant women has not been established. Objectives: The purpose of this study is to determine (1) the association between vitamin D deficiency and the occurrence of (HDP) and (2) whether non-Hispanic Black women (NHB) are at greater risk for HDP due to low vitamin D status. Methods: Pregnant females in the National Health and Nutrition Examination Survey (NHANES) study from 2001 to 2006 were used in this study. Participant’s response to interview questions and laboratory results were taken into account to determine HDP status. Logistic regression was used to determine the association between vitamin D status and HDP. Results: Pregnant women with low vitamin D status (25(OH)D < 20ng/ml) were 1.123 (95%CI: 0.808-1.56) times more likely to have HDP compared to women who were vitamin D sufficient. This association was not significant. NHB women did not show a significant increased risk for HDP. Conclusions: Low vitamin D status during pregnancy may lead to an increased risk for Hypertensive Disorders in Pregnancy. However more research on larger sample size is needed to determine the true extent of the association of vitamin D status with HDP in the general population and that of non-Hispanic Black women.

Hypertension is a risk factor for myocardial ischemia via the promotion of endothelial dysfunction and atherosclerosis (Ogita et al., 2004). Hypertension not only a predisposes the heart to ischemic events, but as shown by clinical and experimental studies, exacerbates the heart’s susceptibility to ischemia-reperfusion injury (Golden et al., 1994; Besík et al., 2007; Snoeckx et al., 1986) due to impairments in regulation of calcium handling, ion homeostasis, and energy metabolism (Galiñanes et al., 2004). Nutraceuticals have demonstrated beneficial and protective effects on both hypertension and ischemia reperfusion injury. Resveratrol, a naturally occurring polyphenol which is present in grapes and wine, acts as a cardioprotective agent and can be used to protect the heart against ischemia reperfusion injury. Here we investigate the effectiveness of chronic dietary resveratrol intake in normotensive and hypertensive rats on protection against ischemia-reperfusion injury, assessed in an isolated perfused Langendorff heart model. Rats ingested either a High dose of 2.7mg/day-which mimicked the resveratrol content in daily supplemental intake levels, a Low dose of 0.027mg/day- which mimicked the resveratrol content in moderate red wine intake, or no resveratrol in the drinking water for 28 days, at which point hearts were excised and mounted on a Langendorff apparatus. Once stable conditions were established all hearts were subjected to 30 minutes of no flow ischemia followed by 2 hours of reperfusion. Interestingly, SHR animals did not exhibit reduced recovery, or increased infarct size as compared to WKY. Infarct size as measured by triphenyltetrazolium chloride staining after 2 hours of reperfusion was significantly reduced in High and Low groups (combined WKY and SHR) as compared to Controls (19.9±0.9 and 19.4±0.8 vs 27.7±0.7 % of baseline, p<0.0001). Left ventricular developed pressure was significantly improved 2 hours post ischemia in both High and Low groups (combined SHR and WKY) compared to Controls (83.1±4.1 and 78.6±3.4 vs.67.9±3.2% of baseline, p<0.01). A higher rate of maximal pressure development was maintained in High and Low groups (combined SHR and WKY) compared to Controls (90.5±4.7 and 95.6±5.0 vs.73.5±4.8% of baseline, p<.05). Resveratrol treatment at a High and Low dose reduced contracture of the myocardium as compared to Control (7.2±3.0 and 6.9±2.9 vs. 20.1±2.9 mmHg- LVEDP, p<0.01). In conclusion resveratrol treatment at both a High and Low dose protects against a decline in cardiac function, and reduces infarct size post ischemia reperfusion. Additionally, tolerance to ischemia reperfusion injury in SHR is not reduced as compared to WKY.

Insulin resistacne and hyperinsulinemia are important risk factors for development of type 2 diabetes mellitus and hypertension. Recently, accumulating evidence has shown that endothelial dysfunction, increases in peripheral vessel resistnce and overactivation of the sympathetic neruvous system contribute to the development of insulin resistance-associated hypertension. The signigicance of cardiovascular regulatory center in the brain stem in pathophysiology of the insulin resistance-induced hypertension, however, has not been explored. Previously studies have proved that increases in superoxide anion (O2£»−) production in peripheral tissue and suppression of nitric oxide (NO) expression in the endothial cell are involved in insulin resistance and hypertension. The nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM) are involved in neural regulation of blood pressure by serving respectively as the primary baroreceptor afferent terminal sites and the location of sympathetic premotor neurons for cardiovascular regulation in the brain stem. Clinically, the peroxisome proliferator-activated receptor (PPAR) agonist is commonly prescribed for the treatment of type 2 diabetes mellitus by activate PPAR£^ to enhance peripheral tissue insulin sensitizing ability, to maintain blood glucose homeostasis. Intriguingly, both animal and human studies revealed that PPAR£^ agonist also possesses blood pressure lowering effect, although the underlying mechanism is not clear. We therefore investigated in the present study the role of NO and O2£»− in the NTS and RVLM in the pathophysiology of the high fructose diet-induced insulin resistacne and hypertension, and to evaluate the potential central antihypertensive effect of PPAR£^ agonist in rats subjected to high fructose diet. The normotensive male Wistar Kyoto rats (WKY) were divided into 4 groups, including 3 experimental group that received 60% high fructose diet for 8 weeks and one control group that received regular chow diet for the same period of time. Within the 3 experimental groups, two of them received oral administration of rosiglitazone or pioglitazone (10 mg/kg/day) at the last two weeks (from week 6 to week 8) and the third group received saline ingestion. Systemic blood pressure was measured by tail vein sphygmomanometer very week and venous blood was drawn every other week to measure blood sugar and insulin level. At the end of the experiment, oral glucose tolerance test (OGTT) was tested and O2£»− and NO production in the NTS and RVLM were quantified. In adult male WKY rats I found that high fructose diet induced insulin resistance, hypertriglycemia and hypertension. Oral administration of rosiglitazone or pioglitazone significantly blunted the hypertension, hypertriglyceridemia, and ameliorated insulin resistance induced by high fructose diet. The high fructose diet also increased tissue level of O2£»− in the NTS and RVLM. PPAR£^ agonist treatment for two weeks did not affect the induced oxidative stress in these two nuclei. NO production was also increased in the NTS and RVLM after high fructose diet for 6 weeks. Oral treatment of rosiglitazone or pioglitazone significantly attenuated NO production after high fructose diet. At the molecular level, protein expressions of the NADPH oxdase subunits (p40phox, p47phox and gp91phox) and superoxide dismutase (cupper/zinc SOD, mitochondrial SOD, extracellular SOD) were not altered in the NTS or RVLM after high fructose diet alone or in addition with rosiglitazone or pioglitazone treatment. In the RVLM, there was a significant increase in neuronal NO synthase (nNOS) expression with concomitant decrease in inducible NOS (iNOS) expression. Oral treatment of PPAR£^ agonist for two weeks significantly suppressed the induced nNOS upregulation and attenuated the induced downregulation of iNOS expression in the RVLM. Together these results suggest that overproduction of O2£»− and NO in the NTS and RVLM may related to the development of insulin resistance-associated hypertension. Oral treatment of PPAR£^ agonist, including rosiglitazone and pioglitazone, may provide antihypertensive protection by superssing the induced-nNOS expression and increasing the induced-iNOS expression in the RVLM.

Proefschrift--Universiteit Leiden, 2003. / Notes bibliogr. en fin de chap.

Thèse d'exercice : Médecine. Pneumologie : Université de Nantes : 2003. / Bibliogr. f. 63-68 [73 réf.].

Thèse d'exercice : Médecine. Imagerie médicale et radiodiagnostic : Université de Nantes : 2005. / Bibliogr. f. 72-88 [167 réf.].

Thesis (M. Med. Sc.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 68-72).

Thesis (M.S.)--University of Delaware, 2009. / Principal faculty advisor: William B. Farquhar, Dept. of Health, Nutrition, & Exercise Sciences. Includes bibliographical references.

Thesis (M.P.H.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 68-69).

Thesis (M.P.H.)--University of Queensland. / Includes bibliographical references.