Dysfunction of in vitro urinary bladder contractility and relaxation in the 6-OHDA rat model of Parkinson's disease.

One of the most troublesome non-motor symptoms in Parkinson's disease is urinary dysfunction. The mechanisms involved in how nigrostriatal neurodegeneration leads to these symptoms are poorly understood. In this study, we have investigated the effects of unilateral 6-OHDA lesioning on local smooth muscle responses of rat urinary bladder tissues. Tissue contractile and relaxatory responses to electrical field stimulation and direct muscarinic (methacholine), purinergic (ATP) and adrenergic (noradrenaline) receptor agonists were investigated using in vitro organ bath experiments. The 6-OHDA-lesioned animals displayed a general reduction in bladder contractility, as well as decreased noradrenaline-induced relaxatory response compared to saline-injected animals. These changes were accompanied by reduced expression of muscarinic M3 and β3-adrenergic receptor proteins, the main functional receptors mediating contractile and relaxatory responses, respectively, in urinary bladder smooth muscle. Further, ATP-induced purinergic responses were increased when normalized to tissue weight and maximum contraction response to high K+ Krebs solution. No changes were, however, seen in purinergic receptor protein expression in the 6-OHDA animals. Our data demonstrate that selective central dopamine loss in the nigrostriatal pathway alters the local smooth muscle function and histology in the urinary bladder. This study gives clues on the local mechanisms behind the troublesome urinary bladder symptoms observed in Parkinson's disease.