Effect of Neuropeptide Y on Isolated Rat Hearts

Neuropeptide Y (NPY) induces coronary vasoconstriction and an associated negative inotropic effect in the isolated rat heart, but it is unclear whether NPY produces these effects directly or through the mediation of other vasoactive substances. This question has been examined in Langendorff-perfused, paced hearts using constant pressure. In 22 dose-response experiments examining single injections of NPY, 0.05-5 nmol, into the coronary perfusate, dose-dependent reduction of flow and developed pressure was observed. NPY, 0.5 nmol or approximately 5 x 10(-8) M, was chosen for further studies. This dose produced close to maximal effects on coronary flow, -22 +/- 5%, and developed pressure, -14 +/- 5% (mean +/- SD). NPY was examined during infusion of the cyclooxygenase inhibitor indomethacin (n = 6) and the 5-lipoxygenase inhibitor RG 6866 (N-methyl-4-benzyloxyphenyl acetohydroxamic acid, n = 6), using a test dose for both agents of 20 micrograms/min (approximately 3 microM) or vehicle (ethanol, 0.01 ml/min, n = 9). NPY reduced coronary flow in all three groups: vehicle 6.2 +/- 1.1 to 4.6 +/- 1.1 ml/min, indomethacin 7.0 +/- 1.1 to 5.7 +/- 1.0, and RG 6866 7.0 +/- 1.6 to 6.1 +/- 1.6; reductions of 25 +/- 7, 19 +/- 5 and 13 +/- 9%, respectively. The flow reduction was attenuated by RG 6866. Developed pressure was significantly reduced by NPY in vehicle 71 +/- 10 to 62 +/- 11 mm Hg, and indomethacin 70 +/- 10 to 64 +/- 11 but not RG 6866 74 +/- 15 to 71 +/- 15 groups, reductions of 13 +/- 3, 9 +/- 9 and 4 +/- 5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)