Regional difference in functional roles of cAMP and cGMP in lower urinary tract smooth muscle contractility

The spontaneous contractile force of muscle strips isolated from rabbit urinary bladder dome, base and urethra was dose-dependently inhibited by isoproterenol, an adenylate cyclase activator through beta-adrenoceptors and also by sodium nitroprusside, a guanylate cyclase activator. The relaxation response by isoproterenol was biggest in urinary bladder dome. Percent relaxation to 10(-4) M isoproterenol was 73.6% in bladder dome, 56.1% in bladder base, and 44.1% in urethra. The relaxation response by nitroprusside was biggest in urethra. Percent relaxation to 10(-4) M sodium nitroprusside was 34.8% in bladder dome, 51.2% in bladder base, and 63.2% in urethra. Cyclic adenosine monophosphate (cAMP) accumulation by isoproterenol was greatest in dome. cAMP levels increased by 150% in bladder dome, by 74% in bladder base and by 80% in urethra after 1 min over basal levels to become stable for 5 min. Cyclic guanosine monophosphate (cGMP) accumulation by sodium nitroprusside was greatest in urethra. cGMP levels increased by 445% in urethra after 1 min over basal levels and by 320% in dome, by 380% in base and by 1,100% in urethra after 5 min over basal levels. Dibutyryl cAMP relaxed the dome, base and urethra. 8-bromo cGMP also relaxed them. These results suggest that the role of cGMP is mainly related to urethral relaxation, whereas the role of cAMP is mainly related to urinary bladder relaxation.