Abstract

Alterations in adrenergic receptor responsiveness in man may be important in the pathogenesis and maintenance of the hypertensive state and in cardiovascular regulation in the elderly. The proposed studies will attempt to elucidate the alterations in alpha- and beta-receptor responsiveness in hypertensive subjects and beta-receptor responsiveness in the elderly. Assays of alpha 1 and beta 2 adrenergic receptor properties on circulating cells will be correlated with determination venous adrenergic responsiveness. The mechanism by which dietary sodium modulates beta-adrenergic responsiveness in hypertension will also be explored. Further, whether a low sodium diet corrects the defect in beta-adrenergic responsiveness in the elderly will be determined. To identify the site of the defect in lymphocyte beta-adrenergic receptor responsiveness in hypertensive and elderly subjects, possible alterations in beta-receptor structure and Gs structure/density will be monitored. Altogether this proposal outlines an integrated approach to the study of altered human adrenergic receptor function in hypertension and aging and may help determine the importance of proposed in vitro biochemical mechanisms in in vivo human adrenergic receptor regulation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL032501-04A1
Application #
3343848
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242

  Publications

Feldman, R D (1992) A low-sodium diet corrects the defect in beta-adrenergic response in older subjects. Circulation 85:612-8
Feldman, R D (1990) Beta-adrenoceptor responsiveness in hypertension: effects of dietary NaCl intake. Br J Clin Pharmacol 30 Suppl 1:55S-60S
Feldman, R D; Brotherton, A; Welsh, M J (1990) Beta-adrenergic-mediated Cl secretion: evidence for additional non-cAMP-dependent pathway of effect. Am J Physiol 259:L426-31
Feldman, R D (1990) Defective venous beta-adrenergic response in borderline hypertensive subjects is corrected by a low sodium diet. J Clin Invest 85:647-52
Feldman, R D (1989) Beta-adrenergic desensitization reduces the sensitivity of adenylate cyclase for magnesium in permeabilized lymphocytes. Mol Pharmacol 35:304-10
Feldman, R D; Christy, J P; Paul, S T et al. (1989) Beta-adrenergic receptors on canine coronary collateral vessels: characterization and function. Am J Physiol 257:H1634-9
Bainbridge, T; Feldman, R D; Welsh, M J (1989) Adrenergic stimulation of inositol phosphate accumulation in tracheal epithelium. J Appl Physiol 66:504-8
Feldman, R D; Fick, R B; McArdle, W et al. (1987) Are lymphocyte beta-adrenoceptors altered in patients with cystic fibrosis? Clin Sci (Lond) 73:407-10
Feldman, R D (1987) Beta-adrenergic receptor alterations in hypertension--physiological and molecular correlates. Can J Physiol Pharmacol 65:1666-72
Ruoho, A E; Clark, R B; Feldman, R D et al. (1987) Photoaffinity labeling in the study of lymphoid cell beta-adrenergic receptors. Methods Enzymol 150:492-502

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