Our long-term research goal is to elucidate the physiological role of histamine in the regulation of renal hemodynamics and renal function. In this proposal we describe experiments designed to test the hypothesis that 1) histamine is a key modulator of renal blood flow autoregulation, 2) histamine-induced changes in renal hemodynamics and renal function are regulated by several enzymatic steps in the metabolic pathway of histamine, 3) histamine, in part, accounts for the renal vasodilation associated with exogenously administered and endogenously released prostaglandins and 4) histamine-induced renal vasodilation is an endothelial cell dependent event. Our experiments will be performed in pentobarbital anesthetized dogs. Renal blood flow will be measured with an electromagnetic flow probe and all drugs will be administered directly into the renal artery. Experiments designed to address a) hypothesis #1 will focus on determining if decreases in renal arterial pressure cause increases in the renal cortical concentration of histamine, b) hypothesis #2 will focus on evaluating effects of inhibitors of histamine synthesis and metabolism on autoregulatory events and on renal function. In addition, effects of these agents on the renal vasodilation produced by histamine, histamine H1 and H2 receptor agonists and histamine metabolism intermediates, C) hypothesis #3 will be directed towards determining the effects of prostaglandins on renal tissue histamine concentrations. We will also determine the effect of H1 and H2 receptor antagonists and of inhibitors of histamine metabolism on prostaglandin induced renal vasodilation and d) hypothesis #4 will be focused on an evaluation of lipoxygenase inhibitors on histamine-induced renal vasodilation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL029021-06
Application #
3340202
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1982-08-01
Project End
1989-07-31
Budget Start
1987-08-01
Budget End
1989-07-31
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Banks, R O (1990) Effects of endothelin on renal function in dogs and rats. Am J Physiol 258:F775-80
Wilfinger, W W; Inscho, E W; Banks, R O (1989) The biological and immunological properties of fractionated atrial extracts from young and old rats. Life Sci 45:2333-42
Hildebrandt, D A; Banks, R O (1988) Effect of atrial natriuretic factor on renal function in rats with nephrotic syndrome. Am J Physiol 254:F210-6
Banks, R O (1988) Vasoconstrictor-induced changes in renal blood flow: role of prostaglandins and histamine. Am J Physiol 254:F470-6
Banks, R O (1988) Effects of a physiological dose of ANP on renal function in dogs. Am J Physiol 255:F907-10
Hildebrandt, D A; Banks, R O (1987) Effect of atrial natriuretic factor on renal function in rats with papillary necrosis. Am J Physiol 252:F977-80
Inscho, E W; Wilfinger, W W; Banks, R O (1987) Age-related differences in the natriuretic and hypotensive properties of rat atrial extracts. Endocrinology 121:1662-70
Inscho, E W; Wilfinger, W W; Banks, R O (1986) Dissociation and enrichment of rat atrial myocytes containing atrial natriuretic factor (ANF). Horm Res 24:26-37
Pollock, D M; Banks, R O (1985) Lower atrial natriuretic activity in the newborn versus adult rat. Miner Electrolyte Metab 11:41-4
Banks, R O; Jacobson, E D (1985) Renal vasodilation with ureteral occlusion and prostaglandins: attenuation by histamine H1 antagonists. Am J Physiol 249:F851-7

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