Several case reports have been filed regarding the latent presentation of hemorrhagic pheochromocytomas in the trauma setting; however, few patients have been found to exhibit these symptoms in the absence of a tumor. In this report, we discuss a patient who sustained blunt abdominal trauma leading to the development of an adrenal hemorrhage and his unexpected sequelae of symptoms. Discovery of the source of the patient's symptoms was delayed secondary to multiple comorbidities in the critical care setting and work-up for other sources such as infection and agitation. Hypertensive urgency was confirmed to be of adrenal etiology with measurement of persistently elevated plasma and urine metanephrines during the hospital course. The patients hypertensive urgency was successfully managed with the use of antisympathomimetics including an esmolol drip, clonidine, and eventually tapered dose of metoprolol. Symptoms improved over time, and repeat CT imaging weeks later showed resolution of the hematoma. Review of literature reveals only one other case of adrenal hemorrhage after blunt force trauma resulting in hemorrhagic psuedotumor. To our knowledge, this is the second such case ever presented. This case is discussed along with the presentation, diagnostic work-up, and treatment of a critically ill patient with an adrenal hemorrhage masked as a pseudotumor.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

No description available.

Different taste preferences and genetic variations may lead to particular food patterns that contribute to nutrient-related health outcomes such as hypertension. The objective of this study was to investigate single polymorphism of taste genes and salt taste perception in order to determine whether single nucleotide polymorphisms (SNPs) in the salt taste receptor genes (SCNN1B, TRPV1) affect salt taste perception in hypertensive participants. A cross-sectional study of 253 adults age 20-82 from each group, hypertensive (49%) and normotensive (51%), were enrolled. Salt taste recognition threshold, food preference score, and salt taste receptor genotype were determined. The hypertensive group had a higher salt taste recognition threshold than the normotensive group. However, there was no correlation between salt taste recognition threshold and salty food preference. Results also provide evidence that the polymorphism TRPV1, rs4790522 with AA genotype is associated with a lower sensitivity threshold of salt taste.

Patients suffering from hypertension often develop non-Insulin dependent diabetes mellitus (NIDDM), a condition caused by Insulin resistance. Though these patients have normal Insulin receptor (IR) and high levels of Insulin in blood, they fail to have IR-mediated signaling essential for glucose uptake and availability. NIDDM usually begins as insulin resistance, a condition in which Insulin Receptor (IR)-mediated signaling that leads to glucose uptake and glucose availability to cells is inhibited even in the presence of high levels of Insulin in blood. Mechanisms for the development of this Insulin resistance in patients suffering from hypertension are unclear. Angiotensin II (Ang II) hormone has been implicated in the pathogenesis of insulin resistance and inhibitors of Ang II receptor AT1 are shown to improve insulin sensitivity. Here we show that in the skeletal muscle tissue of SHR rats, Insulin Receptor (IR) beta- subunit forms a complex with the AT1 receptor and co-immunoprecipitates with IR-beta. Such strong AT1-IR association was not observed in normo-tensive rat tissue. To our knowledge this is the first report that shows AT1 can associate with IR-beta in mammalian tissue and that such association might play a role in the regulation of signaling by IR-beta. We further demonstrate that a 2-hour pre-incubation with Ang II (at concentrations 50pM to 1?ÝM) significantly inhibits 125I-insulin binding to IR in human cell line MCF-7. This effect was not seen when Ang II exposure was performed for shorter periods. The two-hour exposure to Ang II also led to the formation of a protein complex containing AT1 and IR-beta, similar to that seen in skeletal muscle tissue of SHR rats. Both AT1-IR association and differential tyrosine phosphorylation of IR-beta and associated proteins were inhibited when the cells were pre-treated with the AT1 antagonist losartan. These observations suggest that continuous presence of Ang II would result in sequestering IR in the AT1-IR complex and prevent IR from binding insulin. It also coincided with differential tyrosine-phosphorylation of IR beta-subunit and associated proteins, than that generated when IR was activated by insulin. Therefore, we infer that conformational alterations in IR caused by AT1-IR-beta association underlie the development of Ang II-induced insulin resistance. Based on these data we propose a model for AT1-mediated insulin resistance that involves receptor level interaction between the AT1 and the IR. Therefore, Insulin-independent, Ang II-induced tyrosine phosphorylation of IR prevents IR from binding Insulin and contributes to Insulin resistance. The observation that drugs that inhibit Angiotensin II converting enzyme (ACE), or activation of AT1 receptor, not only reduce hypertension, but also induce insulin sensitivity further supports the role for Ang II and AT1 in the development of NIDDM.

Molecular analysis of the cross talk between Angiotensin II (Ang II) and insulin signaling systems reveal that they are multifaceted and occur at cellular level and intracellular level. Experiments were carried out to evaluate the crosstalk between the Ang II receptors-AT1 and AT2 and the Insulin Receptor (IR) to understand the changes in the signaling pathway that could lead to the transition from hypertension to insulin resistance. Transient expression of rat AT2 in CHO cells induced co-immunoprecipitation of the AT2R with IRâ and inhibition of IRâ tyrosine phosphorylation. An AT2-peptide carrying the amino acids 226-363 (that spans 3rd intracellular loop (ICL) and C-terminal cytoplasmic domain) was sufficient for AT2- IRâ interaction in a yeast two-hybrid assay. An orthovanadate-insensitive AT2- IRâ association was also observed in human breast cancer cell line MCF-7. Interestingly, while AT2- IRâ complex formation was insensitive to pertussis toxin (PTX), AT2-mediated inhibition of IRâ phosphorylation was partially sensitive to PTX treatment in MCF-7. To address the mechanism behind the transition of an early hypertensive heart to an insulin resistant status, we investigated the changes that occur at post translational level in the IR and its downstream signaling molecules that modulate insulin signaling. Early hypertension was induced in 10-week old SD rats by 2% NaCl diet in combination with Ang II infusion. Enhanced serine phosphorylation of the IRâ suggestive of dysfunctional insulin signaling was observed in cardiac tissues as a result of the treatment. In addition, an enhanced association of both AT1R and AT2R with IRâ was observed in the heart tissue lysates from hypertensive rat heart. To evaluate the tissue effects of Ang II, we compared the transcriptome of hypertensive rat hearts to the controls. Analysis suggests that the Ang II induces multiple responses in heart tissue that result in changes to the gene expression pattern intended to promote insulin sensitivity and insulin resistance. Taken together our results suggest that exogenous Ang II and moderately high salt diet promote metabolic abnormalities in heart tissue that result in sequestration of IR and modulation of IR signaling, and significant changes in gene expression profile in the hypertensive heart.

No description available.

No description available.