Urodilatin attenuates sympathetic neurotransmission in the rabbit isolated vas deferens without activating guanylyl cyclase.
Natriuretic peptides are produced in cardiovascular, renal and neural tissues and are believed to reduce arterial blood pressure by augmenting sodium and water loss in the urine. Another potential antihypertensive action of these peptides involves a suppression of adrenergic neurotransmission. Atrial, brain and C-type natriuretic peptides suppress sympathetic neurotransmission but no data are available on neuromodulatory actions of urodilatin. This 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 generation in response to electrical stimulation of the vas deferens. Brain natriuretic peptide accelerated the production of cyclic guanosine monophosphate equipotently with its effects on neurotransmission. However, urodilatin failed to increase guanylyl cyclase activity, thus dissociating its effects on neurotransmission from guanylyl cyclase stimulation. None of the natriuretic peptides altered contractile effects of either adenosine triphosphate or norepinephrine, the two putative neurotransmitters secreted from adrenergic nerves in the vas deferens. These data are consistent with the following conclusions: 1) all of the known endogenous natriuretic peptides suppress adrenergic neurotransmission; 2) guanylyl cyclase activation is not required for the inhibition of sympathetic neurotransmission by natriuretic peptides; and 3) inhibitory effects of the natriuretic peptides on neurotransmission result from a suppression of neurotransmitter exocytosis. The novel findings of this study include both the suppression of sympathetic neurotransmission by urodilatin and its biological activity in the absence of guanylyl cyclase activation.
Trachte
G J
GJ
Department of Pharmacology, University of Minnesota-Duluth, School of Medicine, 55812, USA. gtracht1@d.umn.edu
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000294:innervation; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects* / Q000201:enzymology / Q000294:innervation
D004232:Diuretics; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D020097:Natriuretic Peptide, Brain; D000244:Adenosine Diphosphate; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D004837:Epinephrine