Autonomic and sensory nerve modulation of peristalsis in the upper urinary tract

The primary function of the upper urinary tract is to propel urine and various water-soluble toxic compounds from the kidneys to the bladder for storage and evacuation to maintain body ionic balance and contribute to the regulation of blood volume and pressure. The mechanism by which the upper urinary tract propels urine has long been considered to be myogenic in origin as peristaltic contractions in vivo and in vitro (pyeloureteric peristalsis) propagate in a manner little affected by drugs that block nerve conduction or the sympathetic and parasympathetic transmission. However, it is now well established that the release of intrinsic prostaglandins and neuropeptides from primary sensory nerves (PSNs) helps to maintain pyeloureteric peristalsis. Electrical field stimulation of PSNs evokes species-specific positive inotropic and chronotropic effects that have been attributed to release of excitatory tachykinins superimposed on negative inotropic and chronotropic effects associated with the release of calcitonin gene related peptide (CGRP), a rise in cellular cyclic-adenosine monophosphate (cAMP) and a protein kinase A-dependent activation of glibenclamide-sensitive ATP-dependent K⁺ (K_ATP) channels. This review summarises the existing evidence of the nervous control of the upper urinary tract and recent evidence suggesting that the autonomic innervation may indirectly modulate pyeloureteric peristalsis via the activation of PSN nicotinic receptors and via the modulation of K_V7 channels located on interstitial cells within the renal pelvis wall.