ASSIGNMENT

Assignment

Assignment

In illuminate study and also in clinical trials which are carried out during the initial phase of development, the use of torcetrapib is related with an increase in blood pressure.9-13 Certainly, the increase in blood pressure was equivalent to the rise in sodium, bicarbonate and plasma aldosterone in addition to the decrease in plasma potassium which was found during the illuminate trial.8 Moreover, inhibition of CETP was also the objective which was assessed the effectiveness of Dalcetrapib to the heart disease2. Though, the study was brought to an end after one year due to the lack of effects2. The reason of such was that the Dalcetrapib is not related to various collateral effects since it is noted that a little though considerable rise in blood pressure was found for Torcetrapib2.

The traditional view of adipose tissue as a reactive storage organ for fatty acids has been changed by the perception that adipose tissue serves as extremely active endocrine and metabolic organ. It controls glucose and lipid metabolism by generating several humoral mediators which are jointly called adipokine4. Moreover, adipokine is engaged in a lot of pathological and physiological course of actions; for instance, systemic and local inflammation, energy metabolism and weight homeostasis.1-3

Aldosterone is a vital hormone as it has important roles in the directives of balancing the blood pressure and electrolyte. Its common physiological controllers entail K +, adrenocorticotropin and Ang II hormones which can raise secretion of aldosterone both chronically by action on the steroidogenic pathway and extremely by rising phosphorylation and StAR expression; mostly by rising gene expression of CYP11B2 3. Dysregulation in aldosterone secretion shows the way to pathologies, for instance, heart disease and hypertension. Numerous cell culture and animal models build up in order to understand in the better way about the secretion of aldosterone under pathological and normal situations. Studies presents that adipocyte and adipocytokines derived hormones which entail mineralocorticoid and Ang II releasing factors, inflammation, modulate vascular function and hypertrophy through a paracrine mechanism. 11 Pathologically, adipose tissue generates factors which activate vascular smooth muscle cell (VSMC) inflammation and growth.12 In addition to this, physiologically the adipocytes produce indeterminate adipocyte derived relaxing factor that stimulate inhibit vasoconstriction and K_ channels.

It is suggested that adipocyte secretory products generate the secretion of adrenocortical aldosterone12-15. In this context, the evidence which is provided by Rhian Touyz group is that adipocytes is the second source of aldosterone22. This steroidogenic activity was validated with the observation that expresses CYP11B25. The aldosterone which is produced locally may have an autocrine contributing to the adipocyte differenration. On the other hand, it is noted that the raise in adipocyte-secreted aldosterone may lead to increase in blood pressure.

There is an important role which is played by ROS production, mainly from NAD(P)H oxidase, in vascular injury which differentiates the high blood pressure6. Moreover, Ang II enhances expression of NAD(P)H oxidase subunits, stimulates ROS generation in adventitial fibroblasts, endothelial cells, intact arteries and also vascular smooth muscle cells, and initiates commencement of NAD(P)H oxidase [15, ...