VESICAL BLOOD-URINE BARRIER 15

61. Matsumura, S., Taira, N. and Hashimoto, K.: The pharmacolog- ical behaviour of the urinary bladder and its vasculature of the dog. Tohoku J. Exp. Med., 96: 247, 1968.

62. McCarron, J . G. and Halpern, W.: Potassium dilates rat cerebral arteries by two independent mechanisms. h e r . J . Physiol., part 2 , 2 5 9 H902, 1990.

63. Kuschinsky, K., Wahl, M., Bosse, 0. and Thurau, K.: Perivascu- lar potassium and pH as determinants of local pial arterial diameter in cats. A microapplication study. Circ. Res., 31: 240, 1972.

64. Levin, R. M., Wein, A. J. and Monson, F. C.: Evidence for urothe- lial hyperplasia following partial outlet obstruction of rabbit uri- nary bladders. J. Urol., part 2, 151: 3774 abstract 597, 1994.

65. Jacob, J., Ludgate, C. M., Forde, J . and Tulloch, W. S.: Recent observations on the ultrastructure of human urothelium. 1. Normal bladder of elderly subjects. Cell Tiss. Res., 193: 543, 1978.

EDITORIAL COMMENTS

The author suggests some interesting hypotheses bearing on the pathophysiology of the bladder in health and disease. Although it has been known for many years that the urothelium is permeable to various solutes, we tend to forget this fact when trying to explain some of the disease entities that are problematic. The concept that urothelial permeability may alter neuromuscular physiology in health and disease is important and to my knowledge is the primary hypothesis advanced in this article. Unfortunately, some of the ar- guments proposed by the author to substantiate this concept are teleologic and do not particularly enhance his position. For example, when the author uses arguments, such as “capillaries lie directly under the urothelium so that blood plasma is only a few microns away from urine. This fact again indicates blood urine compound exchange,” he does not enhance the position, since this observation is true for any surface in the body and, therefore, it certainly does not indicate exchange. Furthermore, comparing the rat bladder to the human bladder by merely correcting for volume changes is not ap- propriate, since there are other substantive differences between the 2 organs. In any event, the concept I would glean from this article would be that when studying various functions of the bladder in health and disease one should keep an open mind as to a possible role of solute and solvent flow through the urothelium affecting mucosal. submucosal and neuromuscular activity.

W. Scott McDougal Department of Urology Massachusetts General Hospital Boston, Massachusetts

This excellent article presents an important point concerning the regulation of permeability and solute diffusion in the bladder. It is one more piece of the puzzle. Regulation of the blood-urine barrier is a multifactorial phenomenon that begins a t the transitional cell surface (mucus) and ends with solute removal from the tissue by blood vessels. There are those who focus only on tight junctions and cation pumps, which are critical but only 1 component. Mucus (ply- cosaminoglycans) is also an important retardant of solute diffusion and perhaps the major regulator of solute difision in terms of volume. On the other hand, as presented in this article, tissue oncotic pressure, hydrostatic pressure in the vessels and “the countercurrent mechanism” also have an important role in “transmucosal” solute movement to and from the bladder. Once there is diffusion, the washout factor appears necessary to remove cation, such as potas-

explain clinical observations noted in disorders, such as interstitial cystitis, radiation cystitis and detrusor instability.

C. Lowell Parsons Department of Surgery1 Urology University of California, Sun Diego San Diego, California

REPLY BY AUTHOR

Substantive differences between the human and rat bladder as stated by McDougal should not distract from a possible complete recirculation of renal waste within a relatively short period, at least in experimental leakage of the vesical urothelium. Neurogenic, uri- nogenic, hematogenous and exogenous factors, as well as ischemia, obstruction and aging derived changes with subsequent reversible or irreversible pathophysiological leakage and decreased resistance to infection indicate the urothelium to be a multifactorial target. Due to the comparably minimal surface-to-volume ratio, urinary potassium induced frequency and ischemia, a significant recirculation appears never to occur in humans. Questions remain on how far ischemia represents a necessarily preceding event of leakage or whether a urinary factor across a leaking urothelium, a factor originating from an impaired urothelium or long-term absence of distension associ- ated mucosal (vesical) washout due to Frequency induce or amplify ischemia. However, continence as a matter of sociability is supposed to be subject to nonrecirculation as a principle of survival. Accord- ingly, and after a 10-year positive experience, for interstitial cystitis and related syndromes as well as the nonobstructed aging bladder I would recommend rearrangement of the urothelium and the mucosal (vesical) blood flow. Most likely secondary to retention of heparin- binding epidermal growth factor receptors,’ an irreversibly impaired blood-urine barrier (complete denervation, nonneurogenic fibrosis) does not respond to topical dimethylsulfoxideheparin and presently by a reliable test to predict reversibility is not available.

On the other hand, under physiological conditions, preferably, luminal membranes provide compound exchange with blood. There- fore, provided that chronic exposure to solutions other than urine does not affect facilitated normal dynamics of transurothelial net transfers, and once there is no foregoing irreversible d y n a m i c deficiency but normal circulation and capacity, in terminal anuria vesical dialysis could have a promising role as a future therapeutic alternative. When perfomed at the same time, it could markedly save time and/or small bowel tubular length needed for sufficient clear- ance. Unfortunately, even when pretreated with dimethylsulfoxide, patients with terminal anuria show poor clearance. For all of those investigators who ever faced the same challenge this disappointment must have counted as additbnal evidence for urothelial ‘imperme- ability” instead of a poor capacity associated poor mucosal (vesical) blood flow. After receiving a kidney transplant, patients frequently complain of urgency and frequency for several weeks. Because of reversibility, and since topical calcium ion antagonists show no acute effect (in contrast to figure 8 in article), regaining a normal capacity with normal vesical circulation obviously requires an extensive blad- der drill procedure with a specially designed solution. My message is intended to stimulate interest concerning vesical dialysis that could promote acceptance of the relevant impacts of urine and impacts of urine and the blood-urine barrier on urodynamics.

1. Parsons, K. F., Krishman, K. R., SON, B. M., Vaidyanathan, S., Howard, C. V. and van Velzen. D.: Retention of eDidermd growth fador receptor protein in‘ spinal cord injury akociated urothelial proliferation arrest. J. Urol., part 2, 183: 3334 abstract 420, 1995.

sium, that could-i’f not removed-by the vasculature affect smooth muscle and sensory nerves. This countercurrent mechanism helps