Biochemistry of Hypertension and Organ Injury

Mark C. Chappell, Ph.D

The long-term objective of the laboratory is to elucidate the role of the kidney and the renin-angiotensin system (RAS) in the regulation of blood pressure and renal injury.  Our current studies also focus on gender differences regarding the relationship of the RAS to hypertension, tissue injury and salt-sensitivty.  We employ several unique experimental models that either overexpress renin (to activate the RAS) or have reduced expression of the tissue form of angiotensin converting enzyme (tiss-ACE) or attenuated expression of ACE2.  These latter models specifically target two key enzymatic pathways of the RAS that contribute to the formation and metabolism of the bioactive hormones Ang II and Ang-(1-7) in the circulation, heart, kidney and brain.  Current projects specifically address the role of Ang II to regulate the intra-renal RAS as well as the extent that nuclear forms of the Ang II receptor participate in this regulatory process.  Our lab is also investigating the dysregulation of various components of the RAS that may contribute to the development of salt-dependent hypertension and tissue injury, as well as the role of estrogen in modulating the salt-sensitive state.