OBJECTIVE: To assess the in vitro effects of hypoxia on urethral smooth muscle and the role that these may have in the fall in urethral luminal pressure consequent upon interruption of its arterial blood supply. MATERIALS AND METHODS: In eight anaesthetized female Large White pigs, femoral blood pressure, urethral luminal pressure and lamina propria blood flow were recorded before, during and after aortic occlusion. In three animals, changes in urethral intramural oxygen tension were also recorded. Smooth muscle strips taken from the mid-urethra were studied in an organ bath under normal and hypoxic conditions, and in the presence of cyanide. The generation of spontaneous tone and the response to electrical-field stimulation were also examined. RESULTS: Urethral luminal pressure declined biphasically after aortic occlusion, from a mean of 83.8 to 39.0 cmH2O. The initial rapid phase seemed to be related to a decrease in urethral lamina propria blood flow, whilst the slower phase appeared to mirror the observed decline in intramural oxygen tension. In vitro, the high spontaneous tone of the muscle strips was abolished by hypoxia or metabolic inhibition whilst the contractile response to nerve stimulation was preserved. CONCLUSIONS: The decrease in urethral pressure after aortic occlusion appears to have two components, the first mediated through a decrease in vascular filling of the lamina propria and the second as a result of hypoxia-induced smooth muscle relaxation. The in vitro effects of hypoxia upon urethral smooth muscle concur with the changes observed in vivo.
OBJECTIVE: To assess the in vitro effects of hypoxia on urethral smooth muscle and the role that these may have in the fall in urethral luminal pressure consequent upon interruption of its arterial blood supply. MATERIALS AND METHODS: In eight anaesthetized female Large Whitepigs, femoral blood pressure, urethral luminal pressure and lamina propria blood flow were recorded before, during and after aortic occlusion. In three animals, changes in urethral intramural oxygen tension were also recorded. Smooth muscle strips taken from the mid-urethra were studied in an organ bath under normal and hypoxic conditions, and in the presence of cyanide. The generation of spontaneous tone and the response to electrical-field stimulation were also examined. RESULTS: Urethral luminal pressure declined biphasically after aortic occlusion, from a mean of 83.8 to 39.0 cmH2O. The initial rapid phase seemed to be related to a decrease in urethral lamina propria blood flow, whilst the slower phase appeared to mirror the observed decline in intramural oxygen tension. In vitro, the high spontaneous tone of the muscle strips was abolished by hypoxia or metabolic inhibition whilst the contractile response to nerve stimulation was preserved. CONCLUSIONS: The decrease in urethral pressure after aortic occlusion appears to have two components, the first mediated through a decrease in vascular filling of the lamina propria and the second as a result of hypoxia-induced smooth muscle relaxation. The in vitro effects of hypoxia upon urethral smooth muscle concur with the changes observed in vivo.
Authors: C-C Shieh; M E Brune; S A Buckner; K L Whiteaker; E J Molinari; I A Milicic; A C Fabiyi; A Daza; J D Brioni; W A Carroll; K Matsushita; M Yamada; Y Kurachi; M Gopalakrishnan Journal: Br J Pharmacol Date: 2007-04-16 Impact factor: 8.739