The proposed research is designed to examine the physiological and pathophysiological significance of the neural control of renal function in hypertension. How the interaction of environmental and genetic factors, activity of the sympathetic nervous system, and alterations in renal function contribute to the development, maintenance, and exacerbation of hypertension will be investigated in two main ways: 1) examining mechanisms of the acute effects of environmental stress on arterial pressure control mechanisms (brain, kidneys) in conscious hypertensive rat models; and 2) examining the importance of these mechanisms in the pathogenesis of hypertension resulting from exposure to chronic environmental stress. In these studies, environmental stress will be used as a physiological stimulus to activate sympathetic outflow in conscious rats.
Specific Aim #1 will determine whether alpha- or beta-adrenoceptors in the central amygdaloid nucleus mediate the increased renal sympathetic nerve activity and antinatriuresis resulting from acute exposure to environmental stress (air stress) in conscious spontaneously hypertensive rats.
Specific Aim #2 will examine whether the enhanced renal sympathetic nerve activity and antinatriuretic responses to air stress in spontaneously hypertensive rats on high sodium intake are mediated via central nervous system alpha-2 adrenoceptors. Whether the renal vasculature and tubules of spontaneously hypertensive rats on high sodium intake are more sensitive to increases in renal sympathetic nerve activity than spontaneously hypertensive rats on normal sodium intake will also be examined.
Specific Aim #3 addresses the question of whether environmental stress increases renal sympathetic nerve activity and decreases urinary sodium excretion in other conscious hypertensive rat models, i.e., DOCA-salt, Dahl salt-sensitive, and borderline (crossbred SHR x WKY) hypertensive rats.
Specific Aim #4 will examine whether chronic exposure to environmental stress produces or exacerbates hypertension in conscious rats by increasing renal sympathetic nerve activity, thus enhancing renal sodium retention.
Specific Aim #5 will examine whether high sodium diet accelerates the development or progression of hypertension resulting from chronic exposure to environmental stress by further enhancing renal sympathetic nerve activity and renal sodium retention.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035163-04
Application #
3348810
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1986-09-30
Project End
1991-02-28
Budget Start
1989-03-01
Budget End
1991-02-28
Support Year
4
Fiscal Year
1989
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
DiBona, G F; Jones, S Y (1992) Effect of acute NaCl depletion on NaCl-sensitive hypertension in borderline hypertensive rats. J Hypertens 10:125-9
DiBona, G F (1992) Sympathetic neural control of the kidney in hypertension. Hypertension 19:I28-35
DiBona, G F; Jones, S Y (1991) Central alpha 2-adrenoceptor responsiveness in borderline hypertensive rats. J Hypertens 9:543-7
DiBona, G F (1991) Role of the renal nerves in hypertension. Semin Nephrol 11:503-11
Kapusta, D R; Jones, S Y; DiBona, G F (1991) Renal mu opioid receptor mechanisms in regulation of renal function in rats. J Pharmacol Exp Ther 258:111-7
DiBona, G F; Jones, S Y (1991) Renal manifestations of NaCl sensitivity in borderline hypertensive rats. Hypertension 17:44-53
Hatton, D C; Jones, S Y; Johnson, A K et al. (1991) Role of anteroventral third ventricle and vasopressin in renal response to stress in borderline hypertensive rats. Hypertension 17:755-62
DiBona, G F; Sawin, L L (1991) Role of renal nerves in sodium retention of cirrhosis and congestive heart failure. Am J Physiol 260:R298-305
DiBona, G F (1991) Stress and sodium intake in neural control of renal function in hypertension. Hypertension 17:III2-6
Kapusta, D R; Jones, S Y; DiBona, G F (1990) Effects of opioid peptides on neural control of renal function in spontaneously hypertensive rats. Hypertension 15:767-73

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