Alteration of intracellular @entity141 -handling and receptor regulation in hypertensive @entity1283 : insights from XXXX -transgenic @entity35 .

@entity1 @entity15656 @entity712 @entity101 @entity35 @entity19 @entity1283 @entity916 @entity2178 @entity141 @entity67 @entity1002
Abnormal intracellular @entity141 -handling appears to be a major cause of systolic and @entity67 in animals and @entity1 with @entity1283 due to pressure overload and @entity712 . However, the precise mechanisms which cause alteration of @entity141 -handling remain unclear. Several lines of evidence suggest that activation of neurohormonal systems may play a central role. In particular, widespread awareness of the importance of the @entity916 -angiotensin system (RAS) has occurred since experimental and clinical studies have detailed the efficacy of angiotensin-converting enzyme inhibitors in reducing morbidity and mortality in @entity1 with @entity1002 . To evaluate in vivo the role of activated RAS in the regulation of (a) cardiac receptor expression and signal transduction mechanisms and (b) @entity141 homeostasis, transgenic TG(mREN2)27 @entity35 harbouring the @entity19 @entity916 @entity15656 d gene were chosen. These animals develop fulminant @entity101 and @entity1283 at an early age despite low levels of @entity916 in the plasma. High expression of the transgene in the vasculature and the heart is associated with increased local formation of @entity2178 . In the @entity15656 -transgenic model alterations of beta-adrenergic neuroeffector mechanisms, @entity141 -handling and alpha-adrenergic signal transduction are observed which are very similar to those observed in the myocardium of @entity1 with end-stage @entity712 . Moreover, treatment with specific inhibitors of the RAS, such as angiotensin-converting enzyme inhibitors or @entity2178 -receptor antagonists, largely reversed these defects. Studies on TG(mREN2)27 @entity35 may provide new insights into the pathogenesis of @entity101 and mechanisms which promote disease progression to end-stage @entity712 and also may have important implications with regard to therapeutics of @entity712 in @entity1 .
