Urodilatin attenuates sympathetic neurotransmission in the rabbit isolatedvas deferens without activating guanylyl cyclase

Natriuretic peptides are produced in cardiovascular, renal and neural tissu es and are believed to reduce arterial blood pressure by augmenting sodium and water loss in the urine. Another potential antihypertensive action of t hese peptides involves a suppression of adrenergic neurotransmission. Atria l, brain and C-type natriuretic peptides suppress sympathetic neurotransmis sion but no data are available on neuromodulatory actions of urodilatin. Th is study investigates the hypothesis that urodilatin and brain natriuretic peptide inhibit sympathetic neurotransmission by elevating guanylyl cyclase activity. Both brain natriuretic peptide and urodilatin suppressed force g eneration in response to electrical stimulation of the vas deferens. Brain natriuretic peptide accelerated the production of cyclic guanosine monophos phate equipotently with its effects on neurotransmission. However, urodilat in failed to increase guanylyl cyclase activity, thus dissociating its effe cts on neurotransmission from guanylyl cyclase stimulation. None of the nat riuretic peptides altered contractile effects of either adenosine triphosph ate or norepinephrine, the two putative neurotransmitters secreted from adr energic nerves in the vas deferens. These data are consistent with the foll owing conclusions: 1) all of the known endogenous natriuretic peptides supp ress adrenergic neurotransmission; 2) guanylyl cyclase activation is not re quired for the inhibition of sympathetic neurotransmission by natriuretic p eptides; and 3) inhibitory effects of the natriuretic peptides on neurotran smission result from a suppression of neurotransmitter exocytosis. The nove l findings of this study include both the suppression of sympathetic neurot ransmission by urodilatin and its biological activity in the absence of gua nylyl cyclase activation. (C) 2001 Elsevier Science Inc. All rights reserve d.