Alpha-adrenergic regulation of myocardial performance in the exercising dog: evidence for both presynaptic alpha 1- and alpha 2-adrenoceptors.
New evidence supporting both presynaptic alpha 1- and alpha 2-adrenoceptors playing a role in the regulation of myocardial contractile performance in the exercising dog is reviewed. Studies utilized chronically instrumented dogs having sonomicrometers for the measurement of regional wall thickening and transducers for the measurement of left ventricular and systemic hemodynamics. During steady state exercise, either the selective alpha 1-adrenoceptor blocker prazosin (80 micrograms/kg) or the selective alpha 2-adrenoceptor blocker idazoxan (80 micrograms/kg) was infused into the left atrium while exercise continued. Immediately following the administration of either alpha-adrenoceptor blocking agent, there were substantial increases in heart rate, left ventricular dP/dt and regional contractile function as assessed using sonomicrometers, and norepinephrine release by the myocardium increased substantially. beta-adrenergic blockade prevented the heart rate and contractile effects of either alpha 1- or alpha 2-adrenoceptor blocker whereas norepinephrine release was further enhanced. These effects could not be attributed to baroreceptor unloading. In dogs studied under resting conditions with norepinephrine infusion to produce an increase in dP/dt similar to that observed during treadmill exercise, no sympathetic augmentation was observed following either alpha-blocker. Together, these studies provide evidence that both alpha 1- and alpha 2-adrenoceptors participate in the modulation of sympathetic neuronal norepinephrine release in the canine myocardium.
Guth
B D
BD
Seaweed Canyon Laboratory, Department of Medicine, University of California, La Jolla.
Thaulow
E
E
Heusch
G
G
Seitelberger
R
R
Ross
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D005246:Feedback; D019329:Idazoxan; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D005082:Physical Exertion / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine; D011224:Prazosin; D019329:Idazoxan