Inhibitory role of the coronary arterial endothelium to alpha-adrenergic stimulation in experimental heart failure.
The role of the endothelium in regulating coronary alpha-adrenergic tone was evaluated in isolated coronary arterial rings from dogs with and without pacing-induced congestive heart failure (CHF). The maximal contractile response to methoxamine was attenuated approximately 43% (p less than 0.05) in both intact and denuded CHF rings compared with control. Conversely, norepinephrine-induced contractions were diminished 58% in intact CHF vessels and 39% in denuded CHF vessels (p less than 0.05). Denudation did not alter responses to methoxamine but significantly (p less than 0.05) augmented the tension generated by norepinephrine in both control (1.7-fold) and CHF (2.4-fold) arteries. In both intact control and CHF coronary arteries, norepinephrine elicited rapid, transient relaxations that preceded slow, sustained contractions; the initial relaxation phase was endothelium dependent, because denudation eliminated the response. Relaxations to the selective alpha 2-adrenoceptor agonist BHT 920 were also dependent on the presence of an endothelium. At peak CHF, endothelium-dependent relaxations to norepinephrine and BHT 920 were enhanced, whereas relaxations to nitroglycerin and acetylcholine were unaltered. The data suggest that alpha-adrenergic tone in canine coronary arteries is diminished by pacing-induced CHF because of a decrease in alpha 1-adrenoceptor-mediated constriction and an enhanced capacity of the endothelium to antagonize the direct vascular smooth muscle response of norepinephrine through endothelium-dependent, alpha 2-adrenoceptor-mediated relaxations.
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Related Subject Headings
- Receptors, Adrenergic, alpha
- Potassium Chloride
- Norepinephrine
- Muscle, Smooth, Vascular
- Muscle Relaxation
- Methoxamine
- Male
- In Vitro Techniques
- Homeostasis
- Heart Failure
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Receptors, Adrenergic, alpha
- Potassium Chloride
- Norepinephrine
- Muscle, Smooth, Vascular
- Muscle Relaxation
- Methoxamine
- Male
- In Vitro Techniques
- Homeostasis
- Heart Failure