Basic Res Cardio190:348-355 9 SteinkopffVerlag 1995 D. D. Gutterman D. A. Morgan Transmural regulation of myocardial perfusion by neuropeptideY Received: 27 September 1994 Returned for revision: 1 November 1994 Revisionreceived:27 January 1995 Accepted: 27 April 1995 Prof. Dr. D. D. Gutterman(g~) D. A. Morgan VeteransAffairsMedicalCenter Universityof Iowa College of Medicineand CardiovascularCenter Iowa City,Iowa52242, U.S.A. Abstract In vivo studies have shown that sympathetic nerve stimulation improves the transmural distribution of myocardial perfusion by increasing the endocardial/epicardial flow ratio; however, the mechanism of this effect is unknown. During nerve stimula- tion both norepinephrine (NE) and neuropeptide Y (NPY) are released, either or both of which may exert vasoconstrictor effects. The present studies were performed to examine the effects of these two cotransmit- ters on the transmural distribution of myocardial perfusion in a canine model. In anesthetized open-chest dogs, during maximal coronary vas- odilation with intracoronary adenosine, both neuropeptide Y (29.7/xg/min) and norepinephfine (0.5 - 2.0/xg/min) reduced myocar- dial perfusion to a greater extent in the epicardium than in the subendo- cardium. The endo/epi ratio with adenosine alone was 1.11 + 0.02. Norepinephrine increased this by 80 %, neuropeptide Y by 20 %, and the combination of the two by 76 % (P < 0.05 for all three vs. adenosine). Neuropeptide Y alone constricted the coronary vasculature but did not alter transmural flow. Thus neuropep- tide Y preferentially reduces myocar- dial perfusion in the epicardium. We speculate that neuronally released neuropeptide Y contributes impor- tantly to the transmural distribution of myocardial perfusion during sym- pathetic nerve stimulation. Key words Neuropeptide Y- norepinephrine - adenosine - coronary - myocardial perfusion Introduction During conditions, of reduced myocardial flow reserve such as exercise, pharmacological dilation with adenosine, and diminished coronary perfusion pressure, sympathetic nerve stimulation can redistribute transmural myocardial perfusion toward the endocardium (3, 4, 15, 20, 23, 28). However, some studies in which vasodilator reserve is exhausted demonstrate an increase in the endocardial/epicardial flow ratio to nerve stimulation but not to norepinephrine infusion. This raises the possibility that factors other than the release of norepinephrine are responsible for the observed transmural flow distribution. We considered the hypothesis that a neurotransmitter coreleased with norepinephrine contributes to the redis- tribution of coronary blood flow. Neuropeptide Y is a vasoactive peptide found to coexist with norepinephrine in sympathetic nerve vesicles (6, 12, 13). Neuropeptide Y is a potent direct coronary vasoconstrictor, and it potentiates vasoconstriction caused by norepinephrine (10, 17), yet its effects on trans- mural blood flow are unknown (1, 17, 18, 22). In addition, neuropeptide Y decreases the release of norepinephrine by presynaptic inhibition (14, 26, 30). It is possible that