Mechanisms underlying changes in the contents of neuropeptide Y in cardiovascular nerves and adrenal gland induced by sympatholytic drugs.

Neuropeptide Y (NPY) is a recently isolated vasoactive peptide, which is present, together with catecholamines, in sympathetic nerves and in the adrenal medulla. In the present study, we report that pretreatment with sympatholytic agents influences the tissue levels of NPY-like immunoreactivity (NPY-LI) in the guinea-pig. Thus, 24 h after reserpine not only noradrenaline (NA), but also NPY-LI, was depleted in the heart, spleen and the adrenal gland. The levels of NPY-LI in the vas deferens and stellate ganglia, however, were unaffected by reserpine in spite of marked depletions of NA. The reserpine-induced depletion of NPY-LI was probably caused by enhanced nerve-impulse flow and subsequent release from cardiovascular nerves in excess of resupply, since it could be prevented by the ganglionic-blocking agent chlorisondamine. Long-term (6 days) treatment with chlorisondamine reduced the levels of NPY-LI in the stellate ganglion. Short-term treatment (48 h) with guanethidine partially prevented the reserpine-induced depletion of NPY-LI, probably due to inhibition of NPY release. Long-term guanethidine treatment depleted not only NA, but also NPY-LI from the spleen. Pretreatment with the alpha-receptor antagonist phenoxybenzamine did not influence the NA levels but reduced the content of NPY-LI in the spleen via a mechanism that was dependent on intact ganglionic transmission. Since NPY has several cardiovascular actions, changes in NPY mechanisms may contribute to the pharmacological and therapeutical effects of sympatholytic agents.