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

This study tested the hypothesis that exogenous infusion of angiotensin II (ANG II) leads to the release of catecholamines [norepinephrine (NE) and ep inephrine (EPI)] into the cardiac interstitial fluid (ISF) space of dogs wi th 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 muM ANG II at 1 ml/min for 10 min) to right atrial neurons via thei r local arterial blood supply and during electrical stimulation of the stel late 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 corona ry sinus (CS) NE. Electrical stimulation (5 ms, 4 Hz, 8-14 V, and 10 min) o f the stellate ganglia caused a similar increase in ISF NE (P< 0.05), accom panied by a sevenfold increase in CS NE (P< 0.05). ISF EPI increased greate r than sixfold during ANG II infusion (P< 0.05) and during stellate stimula tion. However, during ANG II infusions, aorta plasma EPI levels increased f ourfold in AI dogs, whereas in AC dogs, CS NE and EPI levels were unaffecte d during ANG II infusions. Nevertheless, baseline ISF NE and EPI did not di ffer 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 l iberated into the ISF independent of the adrenal contribution, the amount m atching that induced by electrical stimulation of all cardiac sympathetic e fferent neurons. In contrast, NE spillover into the CS occurred only during electrical stimulation of stellate ganglia. NE release and uptake mechanis ms within the myocardium are differently affected, depending on how the fin al common pathway of the sympathetic efferent nervous system is modified.