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Am J Physiol Heart Circ Physiol 281: H813-H822, 2001;
0363-6135/01 $5.00
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Vol. 281, Issue 2, H813-H822, August 2001

Angiotensin II modulates catecholamine release into interstitial fluid of canine myocardium in vivo

Diane M. Farrell1, Chih-Chang Wei2, José Tallaj2, Jeffrey L. Ardell3, J. Andrew Armour4, Gilbert R. Hageman2, Wayne E. Bradley2, and Louis J. Dell'Italia2

1 Department of Physiology, University of Texas at San Antonio, San Antonio, Texas 78249; 2 Division of Cardiovascular Disease, Department of Medicine, University Station, University of Alabama at Birmingham, Birmingham, Alabama 35294; 3 Department of Pharmacology, East Tennessee State University, Johnson City, Tennessee 37614; and 4 Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada B3H 3J5

This study tested the hypothesis that exogenous infusion of angiotensin II (ANG II) leads to the release of catecholamines [norepinephrine (NE) and epinephrine (EPI)] into the cardiac interstitial fluid (ISF) space of dogs with adrenals intact (AI) (n = 7) and with adrenals clamped (AC) (n = 5). LV ISF samples were collected at 3-min intervals during administration of ANG II (100 µM ANG II at 1 ml/min for 10 min) to right atrial neurons via their local arterial blood supply and during electrical stimulation of the stellate ganglia of open-chest anesthetized dogs. In AI dogs, ANG II caused ISF NE to increase fivefold (P < 0.05) without a significant increase in coronary sinus (CS) NE. Electrical stimulation (5 ms, 4 Hz, 8-14 V, and 10 min) of the stellate ganglia caused a similar increase in ISF NE (P < 0.05), accompanied by a sevenfold increase in CS NE (P < 0.05). ISF EPI increased greater than sixfold during ANG II infusion (P < 0.05) and during stellate stimulation. However, during ANG II infusions, aorta plasma EPI levels increased fourfold in AI dogs, whereas in AC dogs, CS NE and EPI levels were unaffected during ANG II infusions. Nevertheless, baseline ISF NE and EPI did not differ and increased to a similar extent during ANG II infusions in AI versus AC dogs. Thus exogenously administered ANG II increases the amount of NE liberated into the ISF independent of the adrenal contribution, the amount matching that induced by electrical stimulation of all cardiac sympathetic efferent neurons. In contrast, NE spillover into the CS occurred only during electrical stimulation of stellate ganglia. NE release and uptake mechanisms within the myocardium are differently affected, depending on how the final common pathway of the sympathetic efferent nervous system is modified.

norepinephrine; epinephrine


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