Beta-adrenergic antagonists and alpha-adrenergic agonists can reduce cardiovascular, responses to mental stress. Mounting evidence suggests these drugs act in the central nervous system to reduce sympathetic neural outflow. Using direct intraneural recordings (microneurography), I propose to 1) identify neural mechanisms regulating sympathetic responses to stress and 2) compare skin and muscle sympathetic stress responses in borderline hypertensives and normotensives. First: In animals, central beta-2 adrenergic receptor blockade reduces sympathetic outflow during stress. I have shown that acute administration of propranolol (a central and peripheral beta-1 and beta-2 antagonist) reduces sympathetic nerve responses to stress in humans. I will determine the influence of centrally and peripherally acting beta antagonists, and of beta-1 and beta-2 receptor antagonists, on the regulation of sympathetic neural outflow during stress. Second: Acutely, propranolol increases resting sympathetic outflow. Resting sympathetic outflow declines with chronic administration. This may reflect resetting of central or peripheral mechanisms with chronic administration. It is not known whether chronic propranolol administration suppresses sympathetic outflow during stress. I will determine whether chronic beta antagonist administration suppresses sympathetic nerve responses to stress. Third: In animals, centrally administered alpha-2 agonists reduce sympathetic outflow during stress. In humans, alpha-2 agonists reduce plasma norepinephrine responses to stress. This may reflect reduced sympathetic outflow or peripheral effects (e.g., prejunctional modulation of norepinephrine release). I will determine whether an alpha-2 agonist reduces sympathetic nerve responses to stress. Fourth: Mental stress may play a role in the development of hypertension. Recent research has focused on the cardiovascular responses to stress in those at risk for hypertension. For example, there is evidence that borderline hypertensives have exaggerated blood pressure responses to stress. It is not known whether these responses reflect enhanced central sympathetic outflow. I will determine whether sympathetic outflow to muscle and skin during stress is greater in borderline hypertensive vs normotensive individuals.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL043514-03
Application #
3472837
Study Section
Behavioral Medicine Study Section (BEM)
Project Start
1990-04-01
Project End
1995-03-31
Budget Start
1992-04-15
Budget End
1993-03-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Hausberg, Martin; Morgan, Donald A; Mitchell, Jennifer L et al. (2002) Leptin potentiates thermogenic sympathetic responses to hypothermia: a receptor-mediated effect. Diabetes 51:2434-40
Hausberg, Martin; Morgan, Donald A; Chapleau, Mark A et al. (2002) Differential modulation of leptin-induced sympathoexcitation by baroreflex activation. J Hypertens 20:1633-41
Correia, Marcelo L G; Morgan, Donald A; Sivitz, William I et al. (2002) Hemodynamic consequences of neuropeptide Y-induced obesity. Am J Hypertens 15:137-42
Correia, M L; Morgan, D A; Mitchell, J L et al. (2001) Role of corticotrophin-releasing factor in effects of leptin on sympathetic nerve activity and arterial pressure. Hypertension 38:384-8
Mitchell, J L; Morgan, D A; Correia, M L et al. (2001) Does leptin stimulate nitric oxide to oppose the effects of sympathetic activation? Hypertension 38:1081-6
Correia, M L; Morgan, D A; Sivitz, W I et al. (2001) Leptin acts in the central nervous system to produce dose-dependent changes in arterial pressure. Hypertension 37:936-42
Mark, A L; Correia, M; Morgan, D A et al. (1999) State-of-the-art-lecture: Obesity-induced hypertension: new concepts from the emerging biology of obesity. Hypertension 33:537-41
Van De Borne, P; Hausberg, M; Hoffman, R P et al. (1999) Hyperinsulinemia produces cardiac vagal withdrawal and nonuniform sympathetic activation in normal subjects. Am J Physiol 276:R178-83
Haynes, W G; Morgan, D A; Djalali, A et al. (1999) Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic. Hypertension 33:542-7
Haynes, W G; Morgan, D A; Walsh, S A et al. (1998) Cardiovascular consequences of obesity: role of leptin. Clin Exp Pharmacol Physiol 25:65-9

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