The importance of the sympathetic nervous system in cardiovascular control during stressful situations, is axiomatic. Recently, a potent system for modulation of sympathetic activity by endogenous opioid peptides has been described. In the conscious, intact animal, this system is apparently involved with limiting sympathetic activation during blood loss. Although this system may function in a variety of stressful situations, our investigation will focus on its role during hemorrhagic hypotension. The general hypothesis is that endogenous opioid peptides both centrally and peripherally modulate autonomic nervous system function and thus cardiovascular control during periods of elevated sympathetic activity. We will test the following specific hypotheses: 1) The hypotension associated with rapid hemorrhage results from activation of this peptidergic system and the resultant decrease in sympathetic nerve activity; 2) Cardiac afferent mechanisms initiate this depression of sympathetic outflow; (3) Other pressor systems (e.g., renin- angiotensin and vasopressin) are affected by and interact with this peptidergic depressor system; 4) Adrenal release of catecholamines is modulated by opioid peptides through a peripheral action. Since the effects of endogenous opioid peptides are affected by anesthetics, these studies will be performed with indwelling arterial and venous catheters, flow probes and nerve recording electrodes. Plasma and adrenal catecholamines will be measured by HPLC with electrochemical detection. The proposed studies are a natural continuation of our earlier work. They are directed toward an understanding of the role of this peptidergic system in modulation of sympathetic activity, and thus, cardiovascular function.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL031218-04A1
Application #
3342293
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1984-04-01
Project End
1991-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
Graduate Schools
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Schadt, J C; Hasser, E M (2001) Defense reaction alters the response to blood loss in the conscious rabbit. Am J Physiol Regul Integr Comp Physiol 280:R985-93
Schadt, J C; Hasser, E M (1998) Hemodynamic effects of acute stressors in the conscious rabbit. Am J Physiol 274:R814-21
Koch, M A; Hasser, E M; Schadt, J C (1995) Influence of nitric oxide on the hemodynamic response to hemorrhage in conscious rabbits. Am J Physiol 268:R171-82
Jang, W; Schadt, J C; Gaddis, R R (1993) Peripheral opioidergic mechanisms do not mediate naloxone's pressor effect in the conscious rabbit. Circ Shock 39:121-7
Hasser, E M; Schadt, J C (1992) Sympathoinhibition and its reversal by naloxone during hemorrhage. Am J Physiol 262:R444-51
Schadt, J C; Ludbrook, J (1991) Hemodynamic and neurohumoral responses to acute hypovolemia in conscious mammals. Am J Physiol 260:H305-18
Schadt, J C; Hasser, E M (1991) Interaction of vasopressin and opioids during rapid hemorrhage in conscious rabbits. Am J Physiol 260:R373-81
Schadt, J C; Gaddis, R R (1990) Renin-angiotensin system and opioids during acute hemorrhage in conscious rabbits. Am J Physiol 258:R543-51
Schadt, J C (1989) Sympathetic and hemodynamic adjustments to hemorrhage: a possible role for endogenous opioid peptides. Resuscitation 18:219-28
Schadt, J C; Gaddis, R R (1988) Role of adrenal medulla in hemodynamic response to hemorrhage and naloxone. Am J Physiol 254:R559-65

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