Effects of hypoxia and glucose-removal condition on muscle contraction of the smooth muscles of porcine urinary bladder.

On the basis of electrophysiological and mechanical behaviors, smooth muscles are classified into phasic and tonic muscles [9, 13, 25]. Phasic smooth muscles generate action potentials and depolarization with high K+, which induces an initial phasic contraction [8]. Phasic muscles include the ileum, urinary bladder, uterus and vas deferens. In contrast, the excitatory electrical response of tonic smooth muscles is graded depolarization without action potentials. High K+-induced depolarization typically evokes a slowly developing sustained contraction in tonic muscles, which include the aorta and trachea. The contractile diversities among different smooth muscles appear to be attributed to variations depending on oxidative metabolism [4, 10], as well as cellular protein expression [2, 7, 14, 26] and electrophysiological responses [3, 28]. Knull et al. showed that hypoxia inhibited high K+-induced contraction in the guinea pig taenia coli, which included phasic muscles [15]. They suggested that high K+-induced contraction could not be maintained in the guinea pig taenia coli under the aerobic condition. On the other hand, some studies have shown that hypoxia has little effect on the contraction of vascular smooth muscle (tonic muscle), such as the rabbit aorta [4] and carotid artery [17]. These findings are considered to demonstrate that the dependence of muscle contraction on aerobic metabolism differs between the phasic type and the tonic type. In guinea pig urinary bladder, cyanide inhibited high K+-induced contraction with decrease in high-energy phosphate compound (adenosine triphosphate, ATP, and phosphocreatine, PCr) contents [12]. These results suggest that muscle contraction of guinea pig urinary bladder smooth muscle is highly dependent on aerobic metabolism. However, hypoxia decreased oxygen consumption and ATP contents in the rat urinary bladder, but only marginally inhibited carbachol (CCh)-induced contraction [29]. These data indicate that the relationship between contractions and aerobic metabolism in the urinary bladder remains unclear. Because it is very difficult to obtain human bladder tissue, porcine tissue has been used as a substitute, representing a large-animal model, to study the physiology and pathophysiology of the lower urinary tract as its anatomy and function are similar to those of the human urinary bladder [19]. To clarify the species difference in the effects of hypoxia, we focused on a larger animal porcine whose bladder has some structural similarity with that of human. Glucose-free physiological salt solution (PSS) decreased high K+-induced contraction in the guinea pig taenia coli [1, 15, 27]. In contrast, glucose-free PSS did not influence the maintenance of contraction in the porcine carotid artery [17] and rabbit aorta [20]. In bovine trachea smooth muscle (tonic muscle), glucose-free PSS did not affect the maintenance of high K+-induced contraction [11]. Glucose-free PSS decreased contraction of the tonic component to muscarinic agonists and high K+ rather than the phasic component in the urinary bladder of the rabbit [16] and guinea pig [23]. The aforementioned studies imply that the effect of glucose removal differs among smooth muscle types. However, the effect of the removal of glucose on contraction in the porcine urinary bladder is still unclear. Therefore, in the present experiment, we attempted to clarify the role of aerobic metabolism and the effects of removal of glucose on high K+- and CCh-induced contraction in the porcine urinary bladder by measuring muscle tension, reduced pyridine nucleotide (PNred) fluorescence and PCr and ATP contents.