Receptors located in the left ventricle with vagal non-myelinated afferents respond to changes in end-diastolic filling pressure (preload), myocardial tension (afterload), the inotropic state of the heart, and chemical substances. Unlike arterial baroreceptors, it is not known what influence chronic hypertension may have on cardiac and peripheral vascular resistance responses mediated by left ventricular receptors. Therefore, it is the aim of the proposed research to evaluate alterations in the cardiovascular reflex response to the chemical and mechanical stimulation of ventricular receptors in normal and renal hypertensive (RH: one-kidney Goldblatt) conscious dogs. The dogs will be chronically instrumented to measure: 1) arterial pressure (AP), 2) heart rate (HR), 3) left ventricular pressures (LVP, LVEDP), 4) left ventricular diameter (LVD), and 5) renal and iliac blood flows (electromagnetic flow probes). The above cardiovascular parameters will be measured throughout the development of hypertension produced by a 50% reduction in renal blood flow of the sole remaining kidney. Dose-response curves relating AP, HR, and iliac vascular resistance responses to varying doses of intracoronary veratridine (IC-V:.05-1.0 Mug/Kg) will be constructed at 1 week intervals for 6 weeks to analyze the time course of reflex alterations during the development of RH. The HR response to acute aortic occlusion (mechanical stimulation) will also be analyzed during the same time course of RH. Responses to IC-V will be evaluated during 6 weeks of chronic aortic occlusion to evaluate the influence of chronic distension alone on the ventricular receptor reflex. During the 6th week of established RH or chronic aortic occlusion the reflex responses to ventricular receptor stimulation will be analyzed after sinoaortic denervation. Appropriate time control measurements will be made utilizing sham operated, control groups. Reflex rsponses will also be evaluated after angiotensin II blockade. To evaluate the specificity of the IC-V injections terminal, acute experiments will be conducted on all dogs involving recordings of left atrial and left ventricular receptor impulse activity during IC-V and acute aortic occlusions. The significance of the proposed research relates to a new understanding of circulatory reflex control in pathophysiological states such as hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R23)
Project #
5R23HL034302-02
Application #
3448907
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1985-09-30
Project End
1987-09-29
Budget Start
1986-09-30
Budget End
1987-09-29
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
East Carolina University
Department
Type
Schools of Medicine
DUNS #
City
Greenville
State
NC
Country
United States
Zip Code
27858