This research will determine the role of AVP in modulating the cardiovascular response to exercise in cats.
Specific aims are: (1) to determine if electrically-induced static contraction of the hindlimb induces increases in spinal and systemic AVP. If this is the case, we will ascertain if these responses are due, in part, to a contraction- induced neuroendocrine reflex. Consequently, dorsal horn and plasma levels of AVP will be measured at rest and during contraction before and after denervation of the contracting muscle; (2) to investigate the possibility that AVP, released systemically during muscular contraction, contributes to the exercise pressor reflex by its action on the arterial baroreflex. Precisely, the possibility that AVP sensitizes the arterial baroreceptors during exercise will be examined. Thus, changes in MAP and renal sympathetic nerve activity (RSNA) in response to static contraction will be evaluated at a constant carotid sinus pressure. Responses will be compared before and after systemic AVP receptor inhibition, lesion of the area postrema, or selective AVP receptor blockade in the area postrema. AVP blockade in the area postrema will be induced by microinjections of specific AVP receptor antagonists; (3) to determine if AVP acts within the spinal dorsal horn to attenuate the exercise pressor reflex by modulation of its afferent arm. Therefore, the pressor and contractile responses to static contraction will be monitored before and after appropriate intrathecal injection of AVP or its receptor antagonists or microinjection of these drugs into the dorsal horn of the spinal cord. The results of these studies will help identify the mechanisms underlying the action of AVP on the cardiovascular system during exercise and may allow physicians to modify the action of this peptide in conditions where it may be harmful (hypertension, heart failure, or ischemic heart disease).

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL048372-03
Application #
2028742
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1995-01-01
Project End
1998-12-31
Budget Start
1997-04-15
Budget End
1997-12-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California Davis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618