Exogenous angiotensin II does not facilitate norepinephrine release in the heart
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.
|Keywords||Angiotensin II/administration & dosage/*pharmacology, Animals, Dose-Response Relationship, Drug, Electric Stimulation, Female, Heart/drug effects/*innervation/physiology, Hemodynamic Processes/drug effects, Infusions, Intra-Arterial, Kinetics, Male, Myocardial Infarction/pathology, Myocardial Ischemia/metabolism/physiopathology, Myocardium/chemistry/*metabolism, Norepinephrine/analysis/blood/*metabolism, Research Support, Non-U.S. Gov't, Swine, Sympathetic Nervous System/drug effects/physiology|
Lameris, Th.W., de Zeeuw, P.A., Duncker, D.J.G.M., Alberts, G., Boomsma, F., Verdouw, P.D., & van den Meiracker, A.H.. (2002). Exogenous angiotensin II does not facilitate norepinephrine release in the heart. Hypertension. Retrieved from http://hdl.handle.net/1765/9991