Aging, hypertension, and fetal-programmed cardiovascular disease are associated with a functional deficiency of angiotensin (Ang)-(1-7) in the brain dorsomedial medulla. The resulting unrestrained activity of Ang II in brainstem regions negatively impacts resting mean arterial pressure, sympathovagal balance, and baroreflex sensitivity for control of heart rate. The differential effects of Ang II and Ang-(1-7) may be related to the cellular sources of these peptides as well as different precursor pathways. Long-term alterations of the brain renin-angiotensin system may influence signaling pathways including phosphoinositol-3-kinase and mitogen-activated protein kinase and their downstream mediators, and as a consequence may influence metabolic function. Differential regulation of signaling pathways in aging and hypertension by Ang II versus Ang-(1-7) may contribute to the autonomic dysfunction accompanying these states.
All Science Journal Classification (ASJC) codes
- Drug Discovery