Re-innervation of smooth muscle that is transplanted to provide urethral sphincter augmentation.

A number of methods to augment the resistance of the outlet of the urinary bladder and to improve continence have been developed, including the artificial urinary sphincter and the placement of skeletal muscle around the urethra. It has been recently shown in a rabbit model that transplantation of smooth muscle around the proximal urethra reduces incontinence caused by internal sphincter deficiency. In the present work we have investigated the re-innervation of a peri-urethral smooth muscle transplant, and whether re-innervating axons have an appropriate effect when they are stimulated. Detrusor muscle from the dome of the bladder was transplanted to encircle the proximal urethras of rats. Rats tolerated the surgery and transplantation without any signs of compromised health. At 8 weeks the new sphincter was intact and easily recognised. The transplant contracted in response to transmural stimulation (1-5Hz for up to 5min) in a similar way to freshly removed detrusor strips. Contractions were graded with stimulus frequency, they peaked at about 10s and faded to a lower tension that was maintained. The amplitudes of sustained contractions of the transplants were reduced to about 10% by hyoscine and were almost abolished by tetrodotoxin. Histological examination revealed healthy, vascularised smooth muscle in the transplants, similar in appearance to freshly dissected detrusor. Re-innervation was confirmed immunohistochemically for transplanted detrusor muscle and transplants of dartos muscle. We conclude that smooth muscle transplanted to form a new sphincter around the urethra becomes functionally re-innervated and has potential to be used for sphincter augmentation.

Structure, function, and endothelium-derived hyperpolarizing factor in the caudal artery of the SHR and WKY rat.

OBJECTIVE: To quantify structural and functional characteristics of the caudal artery from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats with particular reference to endothelium-derived hyperpolarizing factor (EDHF). METHODS AND RESULTS: Ultrastructural studies showed that the number of myoendothelial gap junctions, smooth muscle cell (SMC) layers, and medial cross-sectional area were significantly greater in SHR than WKY. Intracellular dye labeling demonstrated hyperplasia of SMCs in SHR. Analysis of nerve-mediated excitatory junction potentials recorded in SMCs at the adventitial and luminal borders demonstrated decreased radial coupling of SMCs in SHR. In both SHR and WKY, in the presence of NG-nitro-L-arginine methyl ester and indomethacin, acetylcholine-elicited EDHF was abolished by charybdotoxin and apamin, while iberiotoxin had no effect, implicating the involvement of small and intermediate, but not large, calcium-activated potassium channels. EDHF was abolished by Gap-mimetic peptides, 18beta-glycyrrhetinic acid, and endothelial removal but not affected by the NO scavengers hydroxocobalamin and carboxy-PTIO. CONCLUSIONS: Significant differences in SMC morphology and homocellular and heterocellular coupling exist between the caudal artery of SHR and WKY rats. In the caudal artery of SHR, significantly greater heterocellular coupling compensates for other structural changes in the media to maintain a functional role for EDHF.