The purpose of this study was to determine whether neuropeptide Y has a direct vasoconstrictor effect at low doses, mimicking the physiological plasma concentration on the specific site(s) of coronary arterial microvessels in in situ beating canine left ventricles. Coronary microvessels were directly observed by means of an intravital microscope and video system equipped with a floating objective. Epi-illuminated fluorescence coronary microangiography was performed in open-chest anesthetized dogs (n = 14) to examine the changes in internal diameter of epimyocardial arterial microvessels. Flow velocity of fluorescently labeled microspheres in capillaries was also measured (n = 6). To eliminate secondary effects of neuropeptide Y on coronary microvessels via autonomic nervous modulation, experiments were conducted under pharmacological blockade of the regional autonomic nervous system by intracoronary injection of propranolol, 50 μg/kg; phentolamine, 100 μg/kg; and atropine, 5 μg/kg. Aortic pressure and heart rate were kept constant during the experiments. Intracoronary infusion of three different doses of neuropeptide Y (1, 10, and 100 pmol/kg/min) for 5 minutes significantly constricted small microvessels (less than 100 μm in diameter) (-5.2 ± 1.4%, -8.5 ± 1.5%, and -14.0 ± 1.7%; p < 0.05 versus before neuropeptide Y at each dose), medium microvessels (100-200 μm in diameter) (-5.5 ± 1.6%, -10.6 ± 1.8%, and -16.8 ± 2.1%, p < 0.05 versus before neuropeptide Y at each dose), and large microvessels (greater than 200 μm in diameter) (-3.6 ± 0.6%, -5.8 ± 0.8%, and -10.0 ± 1.1%, p < 0.05 versus before neuropeptide Y at each dose) in a dose-dependent manner. Capillary flow velocity was reduced by 17.2 ± 3.1% by an intracoronary dose of 100 pmol/kg/min of neuropeptide Y (p < 0.05). The present study indicates that low doses of neuropeptide Y exert a homogeneous direct vasoconstrictor effect on various sizes of coronary arterial microvessels and reduce capillary flow velocity. These results suggest that neuropeptide Y may play a physiological role in modulating coronary microvascular tone.
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