Role of bradykinin peptides in ACE2-mediated modulation of neurogenic hypertension

Hypertension is a major risk factor for the development of cardiovascular (CV) and renal diseases. The mechanisms involved in the pathogenesis of human essential hypertension are multifactorial and remain unknown. However, it is now well established that a hyperactive brain renin angiotensin system (RAS) plays a critical role in the development and maintenance of neurogenic hypertension in various experimental and genetic animal models of this disease. The kinins, particularly bradykinin (BK) and Lys-BK, are vasoactive peptides which are present in the brain CV regulatory centers and that play important roles in blood pressure (BP) regulation, pain and inflammation. Several studies suggest that there is an interaction between RAS and kinins in the regulation of BP. ; In this proposal, we hypothesize that neuroinflammation mediated by B1R upregulation is involved in central regulation of neurogenic hypertension and that ACE2 overexpression will attenuate the hypertension by modulation of B1R expression. The data generated by this proposal will clarify the role of BK peptides in neurogenic hypertension and the ACE2-mediated reduction of hypertension, add to the knowledge of our current understanding of neurogenic hypertension and provide new insights for the clinical treatment of hypertension and other CV diseases.

Scholars @ ECU