Underlying mechanisms of urine storage dysfunction in rats with salt-loading hypertension.

Abstract

Spontaneous hypertensive rats provide a genetic model for exploring the pathogenesis of urine storage dysfunction related to hypertension (HT). In humans, however, HT develops by both genetic and environmental factors including lifestyle factors such as a high-calorie diet, excessive salt intake and stress. We investigated the influence of salt-loading on bladder function and the underlying mechanisms of storage dysfunction related to HT. Six-week-old male Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats were fed with a normal or high-salt diet for 12weeks. Micturition parameters were obtained from a metabolic cage. Whole bladders were excised from 18-week-old rats and distended in an organ bath. The releases of adenosine triphosphoric acid (ATP) and prostaglandin E2 (PGE2) from the distended bladder epithelia were measured. Changes in bladder blood flow (BBF) were determined with a laser-speckle-blood-flow imaging system. An increase in mean blood pressure (BP) was noted only in DS rats after salt-loading. During the inactive (sleeping) period, voided volume per micturition gradually increased in DR rats fed a normal or high-salt diet and normal-diet DS rats, while it did not change in the DS rats fed a high-salt diet. Bladder distension significantly increased ATP and PGE2 release from the urothelium in DS rats fed a high-salt diet. BBF was significantly decreased in high-salt-diet DS rats. One mechanism behind the relationship between salt-sensitive HT and urine storage dysfunction may be an increase in ATP and PGE2 release from the urothelium via suppression of BBF.