Date of Award

6-1-1994

Degree Type

Restricted Access Dissertation

Degree Name

Doctor of Philosophy

Field of Study

Biomedical Sciences

Department

Graduate School of Biomedical Sciences

First Advisor

Peter B. Raven

Second Advisor

Patricia A. Gwirtz

Third Advisor

James Caffrey

Abstract

Parker, James B., Functional Heterogeneity in Canine Coronary Resistance Arteries. Doctor of Philosophy (Biomedical Sciences), June, 1994, 89 pages, 21 illustrations, bibliography, 82 titles. Two thirds of the coronary vascular resistance resides in the smallest arteries and investigators have hypothesized that they may respond differently to endogenous vasoactive substances. The arterial responses to norepinephrine, acetylcholine, and adenosine were evaluated in large (>700 μm, n=24), intermediate (400 <> 600 μm, n=24), and small arteries (<300 >μm, n=24). Maximal vessel lumen diameter (Dmax) was determined in CA++ free medium. A reference diameter (84 ± 4.3% of Dmax) was established by re-equilibration in medium containing 2.0 mM Ca++. Arterial maximal responses as a percentage of Dmax to norepinephrine, acetylcholine, and adenosine are given in table 1: Table 1; Large % of Dmax; Inter. % of Dmax; Small % of Dmax; Norepinephrine; 41 ± 2.3; 50 ± 4.2; 83 ± 2.4; Acetylcholine; 96 ± 2.7; 88 ± 3.9; 78 ± 1.9; Adenosine; 71 ± 1.8; 81 ± 4.2; 96 ± 1.4. The sensitivity of canine coronary arteries to norepinephrine, acetylcholine, and adenosine in terms of ED50’s are given in table 2: Table 2; Agonists; Large ED50 μM; Inter. ED50 μM; Small ED50 μM; Norepinephrine; 0.037 ± 0.002; 0.078 ± 0.004; no response; acetylcholine; 0.028 ± 0.003; 0.087 ± 0.005; 0.309 ± 0.03; Adenosine; 0.295 ± 0.002; 0.095 ± 0.004; 0.035 ± 0.03. These data indicate that canine arterial responses to the native agonists norepinephrine, acetylcholine, and adenosine are heterogeneous and that neural control predominates in the larger “transport” arteries while local control predominates in the smaller “distributive” arteries. Responses of small and intermediate isolated canine coronary arteries (lumen diameter 147±42μm, and 531±37μm respectively) to norepinephrine were evaluated after pharmacological or mechanical interruption of endothelial relaxing activity. Following with the nitric oxide synthase inhibitor N-Nitro-L-Arginine Methylester (L-NAME) 10^-5 M the small and intermediate vessels spontaneously constricted to 73±4.1% of Dmax indicating a significant basal release of nitric oxide. After L-NAME or endothelial disruption graded additions of norepinephrine now reduced the vessel diameter in previously unresponsive small arteries. These data suggest that the weak and equivocal response of coronary resistance arteries to norepinephrine results from the competitive dilatory influence of endothelial derived nitric oxide production and not to the absence of norepinephrine receptors.

Comments

Parker, James B., Functional Heterogeneity in Canine Coronary Resistance Arteries. Doctor of Philosophy (Biomedical Sciences), June, 1994, 89 pages, 21 illustrations, bibliography, 82 titles. W 4 P241F 1994

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