Studies on the effect of angiotensin II on norepinephrine release from
sympathetic nerve terminals through stimulation of presynaptic angiotensin
II type 1 receptors are equivocal. Furthermore, evidence that angiotensin
II activates the cardiac sympathetic nervous system in vivo is scarce or
indirect. In the intact porcine heart, we investigated whether angiotensin
II increases norepinephrine concentrations in the myocardial interstitial
fluid (NE(MIF)) under basal conditions and during sympathetic activation
and whether it enhances exocytotic and nonexocytotic ischemia-induced
norepinephrine release. In 27 anesthetized pigs, NE(MIF) was measured in
the left ventricular myocardium using the microdialysis technique. Local
infusion of angiotensin II into the left anterior descending coronary
artery (LAD) at consecutive rates of 0.05, 0.5, and 5 ng/kg per minute did
not affect NE(MIF), LAD flow, left ventricular dP/dt(max), and arterial
pressure despite large increments in coronary arterial and venous
angiotensin II concentrations. In the presence of neuronal reuptake
inhibition and alpha-adrenergic receptor blockade, left stellate ganglion
stimulation increased NE(MIF) from 2.7+/-0.3 to 7.3+/-1.2 before, and from
2.3+/-0.4 to 6.9+/-1.3 nmol/L during, infusion of 0.5 ng/kg per minute
angiotensin II. Sixty minutes of 70% LAD flow reduction caused a
progressive increase in NE(MIF) from 0.9+/-0.1 to 16+/-6 nmol/L, which was
not enhanced by concomitant infusion of 0.5 ng/kg per minute angiotensin
II. In conclusion, we did not observe any facilitation of cardiac
norepinephrine release by angiotensin II under basal conditions and during
either physiological (ganglion stimulation) or pathophysiological (acute
ischemia) sympathetic activation. Hence, angiotensin II is not a local
mediator of cardiac sympathetic activity in the in vivo porcine heart
