Mark Knuepfer, Ph.D. » Investigators

Cardiovascular Research Interests:

Primary area of research:

• Central regulation of the autonomic nervous system
• Role of sympathetic nervous system in hypertension and heart failure

Related areas of research:

• Cocaine toxicity
• Adverse cardiovascular effects of behavioral stress

Summary of cardiovascular research:

My laboratory is studying the causes of hemodynamic response variability to acute stress and to cocaine administration. Our studies have revealed that some rats have greater vasoconstrictor and sympathetic neural responses to behavioral or pharmacological stress. This subset of animals, named vascular responders, is more prone to stress or cocaine-induced hypertension and to cocaine-induced cardiomyopathies.

We are studying this phenomenon from several angles. First, we are examining the central neural pathways and neurotransmitters responsible for greater vascular and sympathetic responses. Second, we are studying the genetic causes of response variability particularly in the hypothalamus and brainstem using microarray analyses. Third, we are developing procedures and analyses that will be used to record from single axons in sympathetic nerves of conscious rats. Fourth, we are examining the effects of chronic down-regulation of specific neurotransmitters in specific sites using siRNA or drug treatments to determine whether we can ameliorate the consequences of experimental hypertension and heart failure. Finally, we are examining the effects of hypertension and heart failure on the sympathetic nerve activity using procedures we have developed to record for weeks in single animals.

Our studies require the use of neuroanatomical, neurophysiological, and hemodynamic monitoring. These studies are designed to improve our insight into the mechanisms by which CNS regulation of the sympathetic nervous system contributes to the development of cardiovascular disease.