Evidence for the involvement of arachidonic acid metabolites in spontaneous and drug-induced contractions of rat urinary bladder.
The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and endogenous arachidonic acid (AA) depletion on spontaneous and drug-induced contractions of the rat urinary bladder have been determined by both in vivo and in vitro experiments. Our results suggest that some AA metabolites (presumably prostaglandins) are involved in the physiologic regulation of the micturition reflex in the rat. In vivo findings indicate that the ability of various NSAIDs to inhibit distension-induced rhythmic contractions is proportional to their anti-inflammatory effectiveness. NSAIDs administration or depletion of endogenous AA at the detrusor muscle level by essential fatty acid-free diet (EFAFD) decreased the responsiveness of the urinary bladder to reflex activation. Topical AA triggered a series of neurogenic rhythmic contractions in the preparation which failed to respond to saline loading. This effect was prevented by NSAID pretreatment. The effect of topical AA was mimicked in NSAID-treated preparations by topical prostaglandins. Both NSAIDs and EFAFD reduced the responsiveness of the rat urinary bladder to acetylcholine and purinergic stimulation in vivo and in vitro. NSAIDs enhanced, while EFAFD reduced, the responsiveness of the isolated bladder to stable cholinomimetics. Responsiveness to KCl was unaffected by NSAIDs or EFAFD. These latter findings indicate that either blockade of AA metabolism along the cyclooxygenase pathway or endogenous AA depletion might alter bladder responsiveness at the postjunctional level. However, because the amplitude of distension-induced rhythmic contractions is unaffected by NSAIDs or EFAFD, it appears unlikely that endogenous prostanoids play a role in excitatory neurotransmission or in tension development during physiological-like activation of the bladder muscle. In vitro findings indicate that both NSAIDs and EFAFD reduce the myogenic contractility and the responsiveness to stretch of bladder muscle. These findings are suggestive that AA metabolites could regulate micturition by enhancing the amplitude of the myogenic contractions of the bladder muscle and, consequently, the discharge of vesical afferents to the central nervous system.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D004032:Diet; D005228:Fatty Acids, Essential / Q000172:deficiency; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007660:Ketoprofen / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D010830:Physostigmine / Q000494:pharmacology; D010894:Piroxicam; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D005228:Fatty Acids, Essential; D006584:Hexamethonium Compounds; D013843:Thiazines; D010894:Piroxicam; D016718:Arachidonic Acid; D013779:Tetrodotoxin; D000244:Adenosine Diphosphate; D007660:Ketoprofen; D010830:Physostigmine; D001241:Aspirin; D007213:Indomethacin