Bladder outlet obstruction secondary to benign prostatic hyperplasia induces numerous changes in bladder morphology, physiology, and pharmacology. These changes have been studied experimentally in various animal models, and while each species has advantages and disadvantages, it is unclear which is most like man. It has been shown that tissue hypertrophy leading to an increase in tissue mass develops rapidly after bladder outlet obstruction. Ischemia induced by the obstruction results in acute muscle dysfunction. The degree of functional impairment is directly related to the degree of tissue hypertrophy. However, the bladder contractile apparatus appears to have a surprising regenerative ability, such that recovery of bladder function becomes obvious 14 days after obstruction. Urody‐namic changes include an increase in urinary frequency and voiding pressure and a decrease in voided volume. Clinically, involuntary bladder contractions are often present. Determination of which of these specific aspects of outlet obstruction the investigator is interested in studying will dictate the selection of the most appropriate animal model.

The current study investigated the relationship between duration of outlet obstruction, magnitude of bladder mass, and functional dysfunction on the rabbit urinary bladder. Following the production of obstruction with the "cuff model", bladder wet weight increased to twice control weight within one week, and then slowly to four times control weight by one month, and remained at this level for the six month period. Bladder capacity decreased significantly by one week but returned to control volumes by one month. The in vitro ability of the bladder to empty in response to field stimulation and bethanechol decreased significantly in the one and two week obstructed bladders and remained decreased for six months. One of the major observations of this study was the relatively large variation of bladder weight and histology observed for the one to six month obstructed rabbits. Although the bladders with mild mass increase (less than 3 gm./kg. body weight) had normal distribution of urothelium and muscular elements, the bladders with moderate mass increase (3 to 6 gm./kg.) had thick extrinsic connective tissue deposits and the bladders with severe mass increase (greater than 6 gm./kg.) had thick extrinsic and intrinsic connective tissue deposits and muscular degeneration. The percentage occurrence of mild, moderate and severe mass increase was approximately the same (58%, 30% and 12%, respectively) for the one, three, and six month groups. The bladders with mild mass increase had normal bladder capacities and increased pressure responses to field stimulation and bethanechol. The bladders with moderate-to-severe mass increase showed enlarged bladder capacities and had progressively smaller pressure responses. As the magnitude of bladder mass increased, the ability of the bladder to empty in response to field stimulation and bethanechol decreased proportionally. We conclude that the functional impairment of the bladder is related to the amount of extrinsic and intrinsic connective tissue and the degree of muscle degeneration.

1 Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (65 mg kg-'). Rabbits were rendered diabetic by injecting alloxan (100mg kg-') into the lateral ear vein. Diabetes was confirmed by a significant elevation of serum glucose in both species 8 weeks after injection. 2 The maximum contraction to noradrenaline (NA), 5-hydroxytryptamine (5-HT) and KCI was markedly diminished in thoracic aortic rings (AR) from diabetic rats with no change in the EC50 of the agonists. There were no differences in the contractile properties of AR from diabetic rabbits to NA, 5-HT or KC1. Diabetes did not alter the responsiveness of AR from the rat to angiotensin II (All).However, AR from diabetic rabbits displayed a decreased maximal contraction and an increased ECO to All. 3 The magnitude of the acetylcholine-induced relaxation to precontracted AR was not different between diabetic and control rats and rabbits. 4 The contractile responses ofAR to NA, 5-HT and KCl were depressed in diabetic rats, regardless of the control tissue to which they were compared. The decrease in maximal contraction to NA, 5-HT and KCI seen in diabetic animals was prevented by insulin replacement. 5 The results demonstrated that while both rats and rabbits exhibited a similar degree of hyperglycemia after treatment with a diabetogenic agent, aortic preparations from the rabbit are not affected in the same way as the aorta from the diabetic rat when exposed to NA, 5-HT and KC1. This feature may be related to the marked differences between the extent of sympathetic innervation of the aorta in the rabbit and rat. Furthermore, the decrease in maximal contraction in rat aorta was nonspecific with respect to agonists since it could also be demonstrated with KCL. Therefore, it follows that the diabetic state may affect processes responsible for contraction beyond the level of receptor activation.

Isoproterenol relaxed KCl‐precontracted rat bladder strips with a pD2 of 7.21 leaving a residual contractile response of 3.2% after 30 μM. The selective β1‐agonist, T‐0509 (pD2 : 6.24, 10.1% residual contraction after 100 μM), β2‐agonist, terbutaline (pD2 : 5.43, 13.7% residual contraction after 100 μM), and β3‐agonists, BRL 37344A (pD2 : 6.60, 17.3% residual contraction after 100 μM), and SR 58611A (pD2 : 5.15, 34.0% residual contraction after 100 μM), also relaxed bladder strips. The relaxant response to isoproterenol was weakly but significantly antagonized by 1 μM propranolol which produced a 3 fold shift of the concentration‐response curve to the right, and significantly antagonized by the β1‐selective antagonist, metoprolol (10 μM, 3 fold shift), and the β2‐selective antagonist, butoxamine (100 μM, 6 fold shift). A combination of 10 μM metoprolol and 100 μM butoxamine caused a 15 fold shift of the concentration‐response curve for isoproterenol to the right. Incubation with the β3‐antagonist, SR 59230A (1 μM), caused a 6 fold shift of the concentration response curve for isoproterenol to the right. The non‐conventional partial agonist, CGP 12177A, weakly relaxed KCl‐precontracted bladder strips (pD2 : 3.31, 51.3% residual contraction after 300 μM); the relaxation was resistant to blockade by 1 or 10 μM propranolol. In the presence of 200 μM propranolol, CGP 12177A (20 μM) or SR 59230A (10 μM) antagonized surmountably the relaxant effects of BRL 37344A. The data suggest that rat urinary bladder body contains β1, β2, and β3‐adrenoceptors, all of which mediate relaxation. British Journal of Pharmacology (1999) 127, 1744–1750; doi: