Neuropeptide Y and sympathetic control of heart contractility and coronary vascular tone.

The effects of neuropeptide Y (NPY) on contractility of the spontaneously beating guinea-pig atrium and transmural nerve stimulation (TNS)-induced efflux of tritium-noradrenaline (3H-NA) were studied in vitro. NPY induced a moderate positive chronotropic and inotropic atrial response, which was resistant to metoprolol. TNS at 2 Hz for 2 s caused an increase in rate and contractile force. These effects were significantly reduced by NPY. NPY also reduced the TNS induced (2 Hz for 20 s), fractional [3H]NA release by 40% without affecting the contractile response. The contractile effects of exogenous NA on the guinea-pig atrium were not affected by NPY. NPY caused a long-lasting increase in coronary perfusion pressure, and also, in high doses, an inhibition of ventricular contractility in the isolated, perfused guinea-pig heart. The perfusion pressure increase to NPY, which most likely reflects coronary vasoconstriction, was resistant to alpha- and beta-adrenoceptor blockade but sensitive to the calcium antagonist nifedipine. A 50% reduction of the vascular NPY response occurred at 10(-9) M nifedipine, which did not influence cardiac contractility per se or the contractile effects of NA. NPY did not modify the increase in ventricular contractility induced by NA. Noradrenaline did not influence coronary perfusion pressure after beta-blockade. Since NPY is present together with NA in cardiac nerves, it may be suggested that NPY is involved in the regulation of NA release as well as the sympathetic control of atrial contractility and coronary blood flow.