Abstract:

The present study explores whether some arachidonic acid (AA) metabolites formed via cyclo-oxygenase or lipoxygenase pathways influence the inotropism of isolated rat urinary bladders evoked by electric field stimulation (EFS), both in presence of or in absence of atropine. The EFS consisted in square wave pulses of 5 Hz, 5 msec duration and supramaximal voltage, applied every 3 min for a period of 10 sec. Acetylsalicylic acid (ASA) at 10-4M, decreased around 30% the magnitude of inotropic responses to EFS and prostaglandin E2 (PGE2, partially at 10-9M and fully at 10-8M), restored control inotropic levels. PGI2 was also active but only at 10-7M); whereas PGF2α, at all concentrations tested (10-9-10-7M), failed to counter act the diminishing effect of ASA. Moreover, dose-response curves for added acetylcholine (ACh) were not modified by ASA. On the other hand, in presence of atropine (10-5M), a diminution of around 40% in the magnitude of control responses to EFS, was detected and when ASA (10-4M) was added to atropine-exposed preparations, the atropine resistant component of the EFS-evoked inotropism, was reduced around 30%. Although recovering effects of added PGs were again observed, they were not identical to those observed in absence of atropine. Indeed, PGE2 fully restored the magnitude of contractile responses but it did so only at concentrations 10 times higher than without the cholinergic receptor blocker. On the other hand, PGI2 as well as PGF2 α, even at 10-7M, were devoid of significant influence. In determining whether lipoxygenase products of AA were also able to modulate the EFS-evoked inotropism, tissue preparations were incubated with nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenases, and tested for contractile responses to electric stimulation. NDGA (10-7M), failed to alter rat urinary bladder inotropic response to EFS, both in presence of or in absence of atropine. Results suggest that the cholinergic, as well as the non-cholinergic components of the EFS-evoked contractions in isolated rat urinary bladders, are modulated by some cyclo-oxygenase formed AA metabolites, particularly certain PGs, like PGE2. © 1987.