Recent studies suggest that altered central dopaminergic (DA) activity contributes to the development of hypertension. The goal of the present research is to test the hypothesis that central DA neurons contribute to cardiovascular control in the normotensive rat and that functional alterations in these neurons are involved in the pathogenesis of hypertension in the spontaneously hypertensive rat of the Okamoto strain (SHR) and the DOCA/NaCl hypertensive rat, two commonly used models of hypertension in which central and peripheral noradrenergic mechanisms are altered. The first study will test the hypothesis that activation of central D2 receptors results in an increase in blood pressure and sympathetic outflow in normotensive animals. This will be accomplished by injecting DA agonists and antagonists into the cerebroventricular system. The second study will identify the specific neurons that mediate the pressor effects of DA, and examine whether these responses are altered in hypertensive animals. This will be accomplished by microinjecting DA agonists and antagonists into specific cardiovascular regulatory regions of the hypothalamus and brainstem. The third study will test the hypothesis that the responsiveness of central monoaminergic neurons to DA is enhanced in hypertensive animals. Specifically, these experiments will examine whether D2 agonist administration differentially effects DA and noradrenaline stores in brain regions of hypertensive compared to normotensive rats. The fourth study will characterize alterations in the release of DA from central DA neurons in SHR and DOCA/NaCl treated rats. These experiments will employ direct in vitro and in vivo analysis of DA release from brain regions important in cardiovascular regulation. The results will provide the first direct demonstration of altered central DA function in an animal model of hypertension. Taken together, these studies will demonstrate the importance of the central DA system in cardiovascular control in normal and hypertensive 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 #
5R29HL039041-03
Application #
3471515
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1987-07-01
Project End
1990-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Jin, H; Yang, R H; Oparil, S (1992) Cicletanine blunts the pulmonary pressor response to acute hypoxia in rats. Am J Med Sci 304:14-9
Jin, H; Yang, R H; Chen, Y F et al. (1991) Atrial natriuretic peptide in acute hypoxia-induced pulmonary hypertension in rats. J Appl Physiol 71:807-14
Chen, Y F; Meng, Q C (1991) Sexual dimorphism of blood pressure in spontaneously hypertensive rats is androgen dependent. Life Sci 48:85-96
Chen, Y F; Meng, Q C; Wyss, J M et al. (1990) NaCl does not affect hypothalamic noradrenergic input in deoxycorticosterone acetate/NaCl and Dahl salt-sensitive rats. Hypertension 16:55-62
Meng, Q C; Chen, Y F; Oparil, S et al. (1990) High-performance liquid chromatographic determination of amiloride and its analogues in rat plasma. J Chromatogr 529:201-9
Yang, R H; Igarashi, Y; Wyss, J M et al. (1990) Dopamine D2 receptors in the posterior region of the nucleus tractus solitarius mediate the central pressor action of quinpirole (LY171555). Brain Res Bull 24:97-103
Meng, Q C; Chen, Y F; Oparil, S (1989) A simple method for concentration of biogenic amines and their metabolites from biological samples for analysis by HPLC-EC. Life Sci 44:1207-13
Meng, Q C; Chen, Y F; Delucas, L J et al. (1988) Effect of steric exclusion on the separation of proteins by hydrophilic size-exclusion chromatography. J Chromatogr 445:29-36
Chen, Y F; Jin, H K; Paul, R et al. (1988) Blunted pressor responsiveness to quinpirole, a specific dopamine D2 receptor agonist, in conscious deoxycorticosterone acetate/NaCl hypertensive rats is related to atrial natriuretic peptide release. J Pharmacol Exp Ther 246:485-92