This proposal is a revised application which will examine the mechanisms whereby renal adrenergic effector mechanisms influence glomerular hemodynamics and tubular functions and determine the extent to which adrenergic influences are mediated by interaction with other intrarenal hormones, angiotensin II and other relevant hormones. Recent studies from this laboratory have demonstrated a strong renal interaction between adrenergic activity and angiotensin II. These studies will utilize 1) renal micropuncture evaluation of glomerular hemodynamics and tubular reabsorption, 2) analysis of glomerular and tubular angiotensin II and adrenergic subtype receptors, 3) analysis of adrenergic activity in the kidney by evaluation of catecholamine output and chromagranin A, a neurovesicle protein and 4) in vitro assessment of mesangial cell contraction responses to hormones and receptors in cells in culture. These studies will examine several issues: 1) We will define the mechanisms whereby adrenergic activity and individual adrenergic receptor subtypes alter glomerular hemodynamics and tubular function, using agonist infusion and adrenergic antagonists during renal nerve stimulation. 2) We will also determine to what extent the glomerular and tubular effects of adrenergic stimulation, defined above, are independent influences or require interaction with intrarenal angtiotensin II. 3) We will also determine mechanisms whereby increased renal adrenergic activity produces increased intrarenal angiotensin, i.e. adrenergic receptor stimulation and/or prostaglandin mediators. Studies will also define adrenergic:angiotensin II synergism at the effector cell, the mesangial cell. 4) We will determine the mechanisms whereby increased angiotensin II activity compensates for the acute and subacute removal of renal adrenergic activity with renal denervation. Finally, we will integrate these studies by determining whether the volume status of the animal conditions the glomerular hemodynamic response to renal nerve stimulation, and the mechanism whereby this modulation occurs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK036692-04
Application #
3235152
Study Section
General Medicine B Study Section (GMB)
Project Start
1986-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1991-06-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Blantz, R C (1993) Glomerular blood flow. Semin Nephrol 13:436-46
Thomson, S C; Gabbai, F B; Tucker, B J et al. (1992) Interaction between alpha 2-adrenergic and angiotensin II systems in the control of glomerular hemodynamics as assessed by renal micropuncture in the rat. J Clin Invest 90:604-11
Thomson, S C; Tucker, B J; Blantz, R C (1991) Effects of beta-adrenergic blockade on the glomerular and tubular response to acute renal denervation. J Cardiovasc Pharmacol 17:397-402
Tucker, B J; Blantz, R C (1990) Acute and subacute prostaglandin and ANG II inhibition on glomerulotubular dynamics in rats. Am J Physiol 258:F1026-35
Munger, K A; Blantz, R C (1990) Cyclooxygenase-dependent mediators of renal hemodynamic function in female rats. Am J Physiol 258:F1211-7
Thomson, S C; Tucker, B J; Gabbai, F B et al. (1990) Glomerular hemodynamics and alpha 2-adrenoreceptor stimulation: the role of renal nerves. Am J Physiol 258:F21-7
Tucker, B J; Peterson, O W; Munger, K A et al. (1990) Glomerular hemodynamic alterations during renal nerve stimulation in rats on high- and low-salt diets. Am J Physiol 258:F133-43
Tucker, B J; Mundy, C A; Blantz, R C (1989) Effects of beta 1-adrenergic blockade on glomerular dynamics and angiotensin II response. Am J Physiol 257:F225-30
Pelayo, J C; Tucker, B J; Blantz, R C (1989) Effects of beta-adrenergic stimulation with isoproterenol on glomerular hemodynamics. Am J Physiol 257:F866-73
Gabbai, F B; Peterson, O W; Prost, J F et al. (1989) Effect of tertatolol on glomerular hemodynamics in the normal Munich-Wistar rat. Am J Hypertens 2:213S-218S

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