Previous experiments have shown that chronic (3 weeks) dietary depletion in dogs was associated with reduction in indices of cardiac performance (ejection fraction and left ventricular wall motion). The importance of sodium depletion in modulating cardiac performance was strengthened by the finding in isolated rat hearts (Langendorff preparation) obtained from normal rats subjected to 3 weeks of sodium deficient diet; inotropic responsiveness to adrenergic stimulation (both beta and alpha) was depressed. Two possible mechanisms will be considered: 1) Alterations in cardiac performance occur through alterations in autonomic nervous system activity. 2) Alteration in cardiac performance is due to alterations in the myocardium (receptors, transmembrane fluxes, adenylate cyclase). These possible effects will be investigated at 3 levels of sodium intake (normal, low and high): a) in isolated hearts of rats to study possible myocardial alterations. These studies will extend our previous observation (reduced responsiveness to alpha and beta adrenergic stimuli) to the following questions: 1) is the reduction of responsiveness linked to alterations in the number of affinity of myocardial adrenergic receptors? ii) Is this reduction restricted to adrenergic stimuli or does it extend to other inotropic influences? b) In conscious dogs to study cardiac performance by using load-independent indices of cardiac contractility (Emax) and their response to reflex and direct sympathetic stimulation as well as to determine cardiac norepinephrine release. These determinations will help identify whether sodium depletion alters cardiac performance by one or more mechanisms. In addition, these studies will also be performed in hypertensive animals and will be compared to the corresponding normotensive groups.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL030684-02
Application #
3341719
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1984-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Type
DUNS #
017730458
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Rossi, G; Bond, M; Fouad-Tarazi, F M (1989) Chronic sodium depletion increases myocardial calcium content in normotensive rats. Am J Med Sci 297:153-7
Nii, T; Fouad-Tarazi, F M; Ferrario, C M et al. (1987) Changes in hemodynamics and myocardial contractility during chronic sodium depletion in conscious dogs. Hypertension 9:III176-80