Mechanisms underlying SNP-elicited inhibition of CCh-induced contraction on goat urinary bladder smooth muscle
Physiology of nitric oxide on urinary bladder is variable and species specific. In the present study, mechanism of inhibitory effect of sodium nitroprusside (SNP) was investigated on goat urinary bladder smooth muscle (UBSM). SNP (10-5 M) could not produce relaxation on CCh (10-5 M) - contracted tissue, but pretreatment of the tissue with the NO donor inhibited the CCh-induced absolute force of contraction. ODQ (10-5 M) and L-NAME (10-5 M) reversed the inhibitory effect of SNP. Calcium channel blocker, nifedipine (10-5 M) and low calcium PSS potentiated the inhibitory effect of SNP. Similarly, non-specific PDE inhibitor theophylline (10-5 M) and zero calcium PSS (replacement of calcium with strontium in PSS) also augmented inhibitory effects of SNP. On the other hand, PLD activator aluminium fluoride (10-5 M) and PKC activator phorbol-12-myristate (10-5 M) reversed the inhibitory effect of SNP. Therefore, in conclusion, the present study provides evidence that SNP - elicited inhibitory effect on goat UBSM is guanylyl cyclase dependent causing decreased intracellular Ca2+ level. Several factors, viz. suppression of G protein and phospholipase D (PLD) activity, inhibition of protein kinase C and either cAMP/cGMP are implicated to SNP-induced reduced level of intracellular Ca2+ in this tissue.