Effects of antihypertensive drugs on sympathetic vascular control in relation to neuropeptide Y

The present paper summarizes some recent studies supporting that neuropeptide Y (NPY) is involved as a cotransmitter or modulator with catecholamines (CA) in peripheral, sympathetic, and cardiovascular control, and that many drugs used for the studies or treatment of hypertensive disorders influence NPY mechanisms both at the pre- and postjunctional levels. Neuropeptide Y is stored in large dense-cored vesicles and coreleased with noradrenaline (NA) from postganglionic, sympathetic nerves, and with adrenaline (ADR) from the adrenal medulla. Neuropeptide Y release occurs mainly upon high stimulation frequencies or during strong sympathetic reflex activation in animals and humans. Neuropeptide Y inhibits nerve stimulation-evoked NA release via a prejunctional action, causes vasoconstriction in most vascular beds in vivo, exerts variable contractile effects, and enhances NA responses on isolated blood vessels in vitro. The NPY effect can occur independently of adrenergic mechanisms and seems to be mediated via specific, high-affinity receptors, where the C-terminal amidation is essential for binding and biological effects. Most evidence favors a local role for NPY in neurotransmission, while systemic plasma levels of NPY are only sufficiently high to induce vasoconstriction under severe stress. Guanethidine inhibits the NPY release from sympathetic nerve terminals. alpha 2-Adrenoceptor agonists like clonidine inhibit the nerve stimulation-evoked NPY release and treatment with clonidine elevates the tissue content of NPY. The alpha 1-adrenoceptor antagonist prazosin does not influence the NPY release to any major extent, while alpha 2-antagonists enhance NPY release. The beta-adrenoceptor antagonist propranolol facilitates nerve-evoked vasoconstriction in the presence of alpha-adrenoceptor antagonists, unmasking "nonadrenergic" responses. Reserpine treatment depletes the tissue content of NPY via increased local release in excess of resupply. The nerve-evoked NPY release that is enhanced after reserpine treatment is related to remaining vasoconstrictor effects. The NA uptake inhibitor desipramine reduces NPY release. Calcium antagonists such as nifedipine inhibit the vasoconstrictor actions of NPY on arteries, but not on veins. The prejunctional inhibitory effects of NPY on NA release from perivascular nerves are not influenced by nifedipine.