Increased penile expression of transforming growth factor and elevated systemic oxidative stress in rabbits with chronic partial bladder outlet obstruction.

There is a growing body of evidence to support the direct link between obstructive bladder dysfunction and erectile dysfunction (ED). However, there have been few pathophysiological studies to determine the relationship between lower urinary tract syndrome (LUTS) and ED. As the transforming growth factor-ß1 (TGF-ß1) that induces the synthesis of collagen in the penile tissues is critical for the development of ED, the first aim of this study was to investigate the expression of TGF-ß1 in the penis from male rabbits with chronic partial bladder outlet obstruction (PBOO). Besides, it has been suggested that oxidative stress plays a significant role in the pathophysiological mechanism of ED. Thus, the second aim of this study was to further investigate whether the urinary or serum oxidative stress markers are involved in chronic PBOO-induced penile dysfunction. A total of 16 male New Zealand White rabbits were separated equally into four groups: a control group and PBOO groups obstructed for 2, 4 and 8 weeks respectively. Using the RT-PCR and Western blot analysis, a progressive increase of TGF-ß1 in penis was found at 2, 4 and 8 weeks after obstruction. Moreover, the biomarkers for oxidative stress or oxidative damage were significantly detected in the penis of rabbits after PBOO, which include the enhancement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and plasma, plasma malondialdehyde (MDA) and total antioxidant capacity (TAC), as well as reduction of glutathione (GSH). On the basis of our results, the increase of TGF-ß1 and elevated systemic oxidative stress may play key roles to contribute to penile dysfunction after chronic PBOO.

Effect of short-term outlet obstruction on rat bladder nerve density and contractility.

1 The present study was designed to investigate the relationship between innervation density and contractile responses to field stimulation and exogenous agonists at early time points after induction of bladder outlet obstruction (BOO) in rats. 2 When compared with sham-operated animals, 1, 3 and 7 days of BOO were associated with a 75%, 80% and 90% increase of bladder weight. Field stimulation caused a frequency-dependent increase in force of contraction. The force of contraction was reduced at each frequency in BOO rats with the greatest decrease after 1 day and a gradual but incomplete recovery thereafter. In contrast, contractile responses to ATP, carbachol and KCl were markedly reduced after 1 day of BOO and fully recovered after 7 days. The neurofilament staining was not altered by 1 day of BOO, but gradually decreased with increasing duration of BOO reaching the lowest levels after 7 days. 3 We conclude that impaired cellular contractility seems to underlie the early reductions of field stimulation-induced contraction, possibly reflecting surgical trauma of the tissue. However, at later time points a reduced nerve density, possibly reflecting a partial denervation, appears to be the main reason for impaired contractile response to field stimulation.

Specificity of the binding of trifluoperazine to the calcium-dependent activator of phosphodiesterase and to a series of other calcium-binding proteins.

Trifluoperazine inhibits the activation of phosphodiesterase by binding to the calcium-dependent activator. To determine further the specificity by which trifluoperazine binds to activator, we compared the binding of trifluoperazine to activator prepared from several species and tissues and to a number of other calcium-binding proteins devoid of activator activity. Trifluoperazine binds to activator prepared from human, bovine, rat and rabbit brain and from chick embryo fibroblasts. In each case, the binding of trifluoperazine to activator was qualitatively similar and related quantitatively to the ability of the preparation to activate phosphodiesterase. Of the other calcium-binding proteins examined, namely, troponin-C, S-100 protein, phospholipase A, phospholipase B and myosin light chain, only troponin-C displayed any significant calcium-specific binding of trifluoperazine. The binding to troponin-C, however, appeared to be different from the binding to activator; whereas the binding of trifluoperazine to actovator showed no cooperativity, the binding to troponin-C showed positive cooperatively. These results and earlier data showing that trifluoperazine fails to bind to a variety of other proteins, indicate that the binding of trifluoperazine to the calcium-dependent activator of phosphodiesterase is selective and suggest that this binding may explain some of the biochemical and pharmacological actions of this antipsychotic agent.

Effect of vaginal distension on blood flow and hypoxia of urogenital organs of the female rat.

Vaginal delivery of children causes traumatic injury to tissues of the pelvic floor and is correlated with stress urinary incontinence; however, the exact mechanism of organ and tissue injury leading to incontinence development is unknown. The purpose of this project was to test the hypothesis that vaginal distension results in decreased blood flow to, and hypoxia of, the urogenital organs responsible for continence, which would suggest an ischemic and/or reperfusion mechanism of injury. Thirteen female rats underwent vaginal distension for 1 h. Thirteen age-matched rats were sham-distended controls. Blood flow to the bladder, urethra, and vagina were determined using a microsphere technique. Hypoxia of these organs was determined by immunohistochemistry. Blood flow to all three organs was significantly decreased just before release of vaginal distension. Bladder blood flow decreased further immediately after release of vaginal distension and continued to be significantly decreased 15 min after the release. Blood flow to both the urethra and vagina tripled immediately after release, inducing a rapid return to normal values. Vaginal distension resulted in extensive smooth muscle hypoxia of the bladder, as well as extensive hypoxia of the vaginal epithelium and urethral hypoxia. Bladders from sham-distended rats demonstrated urothelial hypoxia as well as focal hypoxic areas of the detrusor muscle. We have clearly demonstrated that vaginal distension results in decreased blood flow to, and hypoxia of, the bladder, urethra, and vagina, supportive of hypoxic injury as a possible mechanism of injury leading to stress urinary incontinence.

Factors underlying the increased sensitivity to field stimulation of urinary bladder strips from streptozotocin-induced diabetic rats.

1. The responses of bladder strips from control, streptozotocin-diabetic, and sucrose-drinking rats to electrical field stimulation were investigated. Sucrose-drinking rats were included as additional controls because they have enlarged bladders as a result of non-diabetic diuresis. 2. Bladder strips from diabetic rats developed more spontaneous activity than those from the two control groups. Indomethacin reduced the amplitude and frequency of spontaneous contractions suggesting that they resulted from endogenous prostaglandin formation. Tetrodotoxin (TTX) had little effect, while alpha, beta-methylene ATP caused increases in spontaneous activity. 3. Bladder strips from diabetic rats responded to field stimulation with greater contractions than controls in the absence of antagonists as well as in the presence of atropine and alpha, beta-methylene ATP. Increasing TTX concentrations caused a step-wise depression of the contractile response to electrical stimulation which was not affected by preincubation with either atropine or alpha, beta-methylene ATP. 4. Atropine and indomethacin had no effect on strength-duration curves constructed to measure threshold contractile responses to five pulses stimulation. The curves were shifted to the right by both TTX and alpha, beta-methylene ATP, indicating that the responses were neurogenic in nature and at least partially, the result of stimulation of P2-purinoceptors. In the absence of drugs, bladder strips from diabetics responded at lower voltages and pulse widths than those of control and sucrose-drinking rats, suggesting that they were more excitable. 5. The response curve of bladder strips from diabetics to field stimulation at increasing voltage was shifted upwards and to the left compared to strips from control or sucrose-drinking rats. 6. Bladder strips from diabetics responded to stimulation at increasing pulse width with greater responses than those from control or sucrose-drinking rats. At 1.0 ms pulse width, the TTX-resistant response of strips from diabetic rats was still greater than that of the other groups, indicating that a myogenic component was also involved.7. The data suggest that bladder strips from diabetic rats are more excitable than those of control or sucrose-drinking rats. This may result from diabetes-induced decreases in bladder lipid or other membrane changes, and/or be a result of partial depolarization, perhaps related to diabetic neuropathy.

Group A streptococcal infection in children younger than three years of age.

We evaluated 758 sick children younger than 3 years of age for Group A beta-hemolytic streptococcal (GABHS) upper respiratory infection (URI) to determine the usual clinical presentation of the disease in this age group, indications for culture and the optimal site(s) from which to isolate the organism. GABHS infection was documented in 35 subjects (4.6%). The classic presentation (as proposed in the 1940s) of GABHS URI in children younger than 3 years of age was not confirmed by this study. In 32 of the GABHS cases there were pharyngitis, common cold symptoms or both, and these were associated with acute otitis media 10 times and with otitis media with effusion 3 times. Clinical impetigo was associated with GABHS URI (4 of 32 cases). GABHS URI would not have been documented in 6 of 32 cases if cultures of the anterior nares had not been performed. Children between 18 and 36 months of age were more likely to have GABHS disease than were younger children. Hoarseness and vomiting occurred less frequently in children younger than 36 months with GABHS infection than in those of that age who had non-beta-hemolytic streptococcal illnesses. A history of two or more siblings at home or a family member with a recent streptococcal infection and the presence of irritability, a reddened throat or palate or uvular edema were each associated with GABHS URI. We concluded that sick children between 18 and 36 months of age with a reddened throat should have cultures taken of the throat and anterior nares for GABHS.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of diabetes mellitus on glucose utilization by the rat urinary bladder.

Streptozocin-induced diabetes in rats causes changes in urinary bladder function and increases the responsiveness of isolated bladder strip preparations to contractile agents and field stimulation. We monitored the role of extracellular glucose in the contractile responsiveness of bladder body strips from control, 2-month diabetic, and sucrose-drinking rats to the muscarinic agonist bethanechol. Consumption of sucrose and induction of diabetes caused increases in bladder mass compared with that of controls. In the presence of normal glucose levels (5.6 mmol/L), bladder strips from diabetic rats responded to bethanechol with significantly larger responses than those from control or sucrose-drinking rats. Removal of glucose from the bathing medium caused time-dependent decreases in contractile response of bladder strips from all groups; there were no differences in the percent decrease in response between the three groups. The presence of insulin (100 mU/mL) had no effects on contractile responsiveness or the rate of decline of response. Following return of glucose to the medium, there were progressive increases in contractile responsiveness in all groups, which returned to original contractile values within 60 minutes and were unaffected by insulin. Pyruvate (9.1 mmol/L) was able to substitute for glucose in maintaining the contractile responses. Increasing the glucose concentration of the medium to 30 mmol/L had no effects on contractile responses. Unstimulated bladder adenosine triphosphate (ATP) and creatine phosphate concentrations were similar in control, diabetic, and sucrose-drinking rats. In conclusion, changes in glucose utilization and high-energy phosphate levels cannot explain the increased contractile responsiveness of bladder body strips from diabetic rats to contractile agents.

The effect of angiotensin II and indomethacin on uterine artery blood flow in pregnant monkeys.

In experiments performed in anesthetized monkeys in the third trimester of pregnancy, mean maternal arterial blood pressure was continuously monitored, the uterine artery blood flow was measured with an electromagnetic flow probe, and prostaglandin levels were assayed in the uterine venous effluent. After inhibition of prostaglandin systhesis with indomethacin, the mean arterial blood pressure in response to angiotensin II was greater than the response prior to indomethacin treatment, and an increase in uterine artery blood flow was prevented. These findings are consistent with the suggestion that prostaglandins mediate the uterine artery blood flow response to angiotensin II, as well as modifying the maternal systemic blood pressure response.

Plasma estradiol window and urinary estriol glucuronide determinations for monitoring menotropin induction of ovulation.

The plasma estradiol response is maximal 8--10 hours following mentropin injection. To obtain closer control, a menotropin protocol using 5 PM--8 PM injections and 8 AM blood sampling with a plasma estradiol window of 1000--2000 pg/ml was evaluated with simultaneous calibration of a urinary estriol glucuronide radioimmunoassay. One hundred twenty-eight paired urine and plasma samples were assayed in 48 cycles. In 26 cycles with paired samples on the day of human chorionic gonadotropin (hCG) injection, there were no cases of severe hyperstimulation, 2 cases of moderate hyperstimulation, and 11 pregnancies (42% of cycles given hCG). A window of between 40 and 100 micrograms/day of urinary estriol glucuronide corresponded to the 1000--2000 pg/ml plasma estradiol window by regression analysis. The pregnancy and hyperstimulation rates were compared with those observed in protocols previously published. Radioimmunoassay of urinary estriol glucuronide is faster and simpler than radioimmunoassay of plasma estradiol.

Contractility and phenotype transitions in serosal thickening of obstructed rabbit bladder.

Partial outlet obstruction of rabbit bladder induces serosal thickening and smooth muscle (SM) cell hypertrophy that are accompanied by phenotypic changes in the expression of cytoskeletal and cytocontractile proteins. In the present study, we compare the observed progressive phenotypic changes with the contractile responses of strips of the thickened serosa. At 15 days after partial outlet obstruction, although cells in thickened serosa demonstrate the presence of nonmuscle (NM) myosin of A-like type, vimentin, and SM alpha-actin, no contractile responses of this tissue were noted. At later times (30 days), this tissue expressed in addition SM myosin, and this pattern was paralleled by the development of KCl-stimulated contractility. It is only after 60 days that the serosa demonstrated the expression of desmin, phosphoglucomutase (PGM)-related protein, and was locally negative for NM myosin, indicating a maturation toward adult SM cells. Concomitant to this phenotypic change, the response to KCl increased, and a bethanechol-stimulated contractile response developed. At no time period did the serosal layer react with anti-synaptophysin or anti-neurofilament proteins nor did the strips respond to field stimulation (via release of neurotransmitters), showing that SM cell differentiation and development of contractile responses during serosal thickening are independent of innervation.

The effect of dilevalol on cardiac autonomic neural discharge, plasma catecholamines, and myocardial beta receptor density associated with coronary occlusion.

Cats anesthetized with alpha chloralose received saline or dilevalol (1 mg/kg, IV) during a 10-minute infusion. Fifteen minutes later, the left anterior descending coronary artery was subjected to coronary occlusion 2 mm below its origin. Regional differences in the beta receptor densities were found for the atria and ventricles and for the areas within the left ventricle in cats with no coronary occlusion and dilevalol or saline. The variation in beta receptor density distribution may be related to functional differences. Coronary occlusion and saline or dilevalol did not modify the myocardial beta receptor density regional distribution. Mean times to arrhythmia and death in five saline cats were 5.8 +/- 3.6 (N = 3) and 5.4 (N = 2) minutes; three cats were killed 6 hours after coronary occlusion. In five dilevalol cats the times to arrhythmia and death were 2.2 +/- 0.8 (N = 5) and 75.9 +/- 70.7 (N = 4); 1 cat was killed. Dilevalol induced a significant decrease in blood pressure and heart rate prior to coronary occlusion. Coronary occlusion decreased blood pressure and heart rate in both groups. Twenty-five minutes after dilevalol but prior to coronary occlusion, postganglionic cardiac sympathetic neural discharge decreased to 81%. In the minutes prior to arrhythmia, postganglionic cardiac sympathetic neural discharge was 95% and was significantly increased to 121% 3 minutes after coronary occlusion. The postganglionic cardiac sympathetic neural discharge values after coronary occlusion were similar to those in the saline cats. Dilevalol depressed postganglionic cardiac sympathetic neural discharge prior to coronary occlusion but did not prevent the nonuniform (i.e., increases, decreases, or no change) discharge in the postganglionic cardiac sympathetic neural discharge associated with coronary occlusion-induced arrhythmia. Norepinephrine and epinephrine values in saline cats increased the first 5 minutes after coronary occlusion; this increase was associated with arrhythmia. Norepinephrine and epinephrine values from minute 15 to minute 360 did not differ from control. Dilevalol prevented the increase in norepinephrine and epinephrine levels associated with arrhythmia and death.

The effect of chronic timolol in an animal model for myocardial infarction.

The effect of no drug or timolol (5 mg/kg, PO, for 1, 2, or 8 weeks on postganglionic cardiac sympathetic neural discharge, blood pressure, heart rate and beta-receptor density after acute coronary occlusion of the left anterior descending artery was compared. Beta-receptor density, determined by binding of 3H-dihydroalprenolol, was examined in the myocardium (LA = left atrium, RA = right atrium, LV1 = proximal and LV2 = distal left anterior descending artery distribution, LV3 = posterior left ventricle, S = septum, and RV = right ventricle). In control cats (no coronary occlusion or timolol) beta-receptor density of LV2 and LV3 was greater (P less than .05) than LA, RA, LV1, and RV. LV3 was greater (P less than .05) than S and RA, and LA was less than S. Longer treatment with timolol increased beta-receptor density. When compared with no timolol, beta-receptor density was greater in RA after 8 weeks and in LV1 after 2 weeks and not different in LV2 and S. Beta-receptor density and LV3 and RV were greater after 8 weeks than after 1 week or no timolol. Spearman rank correlation coefficients between dose and beta-receptor density revealed an increase (P less than .05) for all heart areas. Heart rate did not vary before timolol and was decreased after all doses of timolol. Timolol increased the mean times to coronary occlusion-induced death although the increase was not statistically significant. Timolol did not prevent postganglionic cardiac sympathetic neural discharge associated with arrhythmia. Timolol may increase beta-receptor density and decrease synaptic norepinephrine, causing a decreased release per cardiac sympathetic nerve impulse. Alternatively, molecules of timolol may accumulate in nerve endings and be released in greater concentrations at the receptors. This could explain the protection against coronary occlusion-induced arrhythmia and death.

Autonomic innervation of rabbit urinary bladder following estrogen administration.

The effects of estrogen administration on the autonomic innervation of the rabbit urinary bladder were studied. Immature female white rabbits were injected twice daily with estrogen (150 microgram./Kg.) for four consecutive days. Control animals received injections of vehicle alone. The adrenergic innervation was identified using the glyoxalic acid method of catecholamine histofluorescence. The cholinergic innervation was visualized utilizing specific acetylcholinesterase staining. Additionally, the effect of estrogen administration on the response of smooth muscle strips of urinary bladder to specific autonomic agonists was determined. Estrogen administration induced a moderate increase in the adrenergic innervation of the rabbit bladder detrusor, whereas no change could be observed in the cholinergic innervation. It should be noted, however, that whereas the adrenergic innervation in the bladder of the control animal was sparse, the cholinergic innervation in the bladder body was quite dense. Estrogen induced a marked increase in the response to alpha-adrenergic (methoxamine) and muscarinic cholinergic (bethanechol) agonists. No alterations were noted in the response to beta-adrenergic agonists (isoproterenol). These findings indicate that the urinary bladder responds as a target organ for estrogen-induced alterations in autonomic innervation.

Nitrofurantoin not surface active agent in rabbit urinary bladder.

It has been recently suggested that nitrofurantoin may induce symptoms of interstitial cystitis by acting as a surface active agent that destroys glycosaminoglycan (GAG) on the bladder surface. Evidence accumulated over the past decade has demonstrated that the bladder surface GAG prevents bacterial adherence. In this experiment, exposure of the bladder lumen to nitrofurantoin at more than twice the therapeutic concentration did not destroy the bladder GAG layer (as evidenced by periodic acid-Schiff histochemistry) nor increase bacterial adherence as did a true surface active agent (Triton X-100). Acid treatment as well as all tested organic solvents except 50% dimethyl sulfoxide (DMSO) also removed the bladder GAG layer and increased bacterial adherence. These results indicate that neither nitrofurantoin nor 50% DMSO has adverse effects on the bladder surface and thus is unlikely to initiate the interstitial cystitis symptom complex by means of surfactant activity.

Correlation of ischemia/reperfusion or partial outlet obstruction-induced spectrin proteolysis by calpain with contractile dysfunction in rabbit bladder.

OBJECTIVES: In the rabbit, both experimental ischemia and partial outlet obstruction of the urinary bladder induce similar dysfunctions with regard to the contractile responses to both field (neuronal) stimulation and postsynaptic receptor stimulation. Circumstantial evidence indicates that the pathologic response to both conditions is related to two connected processes-tissue ischemia and reperfusion injury-that result in a marked increase in intracellular calcium ([Ca2+]i), followed by the activation of the Ca(2+)-dependent neutral protease calpain. Calpain activation results in the proteolysis of specific membrane proteins, including those of neuronal membranes (resulting in progressive denervation of the detrusor) and the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), resulting in the previously reported decrease in SERCA. The current study is designed to generate direct support for the theory that both ischemia and partial outlet obstruction result in the activation of calpain. METHODS: Separate sets of rabbits were subjected to 1 or 2 hours of ischemia, followed by reperfusion for different lengths of time, or partial outlet obstruction for different lengths of time. We determined the state of calpain activation by quantitating tissue proteolysis of alpha-spectrin by Western blot analysis. Correlative organ bath studies were conducted to observe the contractile responses of bladder strips to field stimulation and bethanechol administration. RESULTS: (1) Sixty minutes of ischemia followed by 30 minutes of reperfusion resulted in (a) a reduction in the contractile responses to field stimulation and bethanechol (89% and 57%, respectively), and (b) a 72% decrease in native alpha-spectrin, with a concomitant 300% increase in its breakdown products (BDPs). Neither alpha-spectrin nor its BDPs had returned to control levels after 72 hours of reperfusion. (2) Twenty-four hours after the creation of a partial obstruction, alpha-spectrin BDP levels were increased 330%, then gradually fell to 130% of control levels by 14 days after obstruction. Concomitantly, the native alpha-spectrin level was decreased 74% 24 hours after obstruction and remained low through 7 days after obstruction. At 14 days after obstruction, the alpha-spectrin levels had recovered to 75% of control levels. CONCLUSIONS: These findings suggest that Ca(2+)-dependent proteolysis of the preferred calpain substrate alpha-spectrin in urinary bladder tissues is increased significantly by both ischemia/reperfusion and partial outlet obstruction. Temporally, proteolysis precedes the reduced muscle function resulting from these pathologic conditions.

Escherichia coli adherence to anion exchange resin. In vitro model for initial screening of potential antiadherence agents.

The first step in developing a bladder infection is attachment of bacteria to the bladder epithelium. Removing the bladder mucin increases bacterial adherence up to a thousand-fold, and this increase can be prevented by pretreating the mucin-deficient bladder with heparin. To develop a rapid, in vitro antiadherence screening assay, we studied the adherence of Escherichia coli to various chromatography resins and the ability of heparin and other agents to antagonize this attachment. The results can be summarized as follows: Although E. coli attached to all resins, only the adherence to the anion exchange resin was inhibited by heparin (up to 95%). Agents which did not effect E. coli adherence to the resin did not affect attachment to the bladder. Agents which inhibited E. coli adherence to the bladder also inhibited E. coli adherence to the resin. Similar to the effect of heparin on E. coli attachment, the adherence of Klebsiella ozaene, Proteus mirabilis, and Streptococcus fecalis to both bladder epithelium and anion exchange resin were also antagonized. These studies indicate that the adherence of E. coli (as well as other bacterial species) to anion exchange resin responds to heparin and other chemical agents in a similar manner as does adherence to the mucin-deficient rabbit urinary bladder. Because of the ease and rapid nature of this in vitro assay, it serves as a useful screen for potential bacterial antiadherence agents and could be used to help elucidate mechanisms of bacterial attachment.

Effects of pregnancy on urethral and bladder neck function.

Pregnancy and menopause induce morphologic as well as functional changes in the female urethra. Symptoms of bladder irritation (frequency, urgency) and incontinence are frequent findings in these conditions and are considered to be due to alterations in the distribution of autonomic receptors induced by the changes in the hormonal milieu. In the present study, the functional responses to field stimulation (FS) and autonomic agonists of the bladder neck and urethra of pregnant, and virgin New Zealand White rabbits were compared using isolated muscle strips. Passive length-tension studies demonstrated a significantly greater compliance of strips (bladder neck and urethra) from pregnant rabbits than from virgin rabbits. FS elicited frequency dependent contractile responses in all strips. Phentolamine was significantly more effective at inhibiting the field stimulated contractile response of urethral strips from pregnant than from virgin rabbits. Atropine was significantly more effective at inhibiting the response to FS of strips isolated from bladder necks of virgin rabbits than in strips isolated from pregnant rabbits. Atropine was significantly less effective at inhibiting the response to FS of strips isolated from urethras of pregnant rabbits than of strips from virgin rabbits. Strips of bladder neck and urethra isolated from virgin rabbits responded with significantly greater contraction to phenylephrine than strips isolated from pregnant rabbits. The magnitude of field stimulated relaxation was significantly greater in urethral strips than in bladder neck strips, and also greater in urethral strips isolated from virgin rabbits than in strips isolated from pregnant rabbits. In conclusion, pregnancy induces profound hormonal changes which, in turn, result in the alteration of the compliance and functional responses of the bladder neck and urethra to various forms of autonomic stimulation and relaxation.

Biochemical evaluation of obstructive bladder dysfunction in men secondary to BPH: a preliminary report.

OBJECTIVES: In the rabbit, two of the major cellular alterations that mediate bladder dysfunction secondary to partial outlet obstruction are a decreased ability of the sarcoplasmic reticulum (SR) to store and release Ca2+, and mitochondrial dysfunction. The objective of the current study was to determine whether SR and mitochondrial dysfunctions are associated with symptomatic benign prostatic hyperplasia (BPH) in men. METHODS: Bladder biopsies were obtained from men with symptomatic BPH and from age-matched men with no urologic dysfunction. Each biopsy was analyzed for the following enzyme activities: malate dehydrogenase and citrate synthase (mitochondrial markers) and the sarcoplasmic reticular enzyme Ca2+ -dependent adenosine triphosphatase (ATPase). These values were compared with the enzyme activities of control rabbit bladder smooth muscle and bladder smooth muscle obtained from rabbits subjected to 2 weeks of partial outlet obstruction. RESULTS: The enzymatic activities of all three enzymes are significantly lower in human bladder smooth muscle than in rabbit bladder smooth muscle. The maximal activities of all three enzymes are significantly lower in human bladder samples obtained from men with diagnosed obstructive uropathy than in men of equal age with no urologic dysfunction. CONCLUSIONS: These studies demonstrate that similar to the response of the rabbit to partial outlet obstruction, obstructive dysfunction secondary to BPH is characterized by mitochondrial and SR dysfunction.

Regional distribution of myocardial beta-adrenoceptors in the cat.

The purpose of this study was to delineate the distribution of beta-adrenoceptor density in the cat heart, with an emphasis on areas within the left ventricle. beta-Adrenoceptor densities, determined for hearts obtained from five cats, were not significantly different in the left and rights atria, i.e. 47.6 +/- 7.2 and 32.8 +/- 7.5 fmol/mg protein, respectively. beta-Adrenoceptor densities for the septum and right ventricle were 105.4 +/- 15.0 and 65.0 +/- 14.0 fmol/mg protein, respectively. The beta-adrenoceptor density for the proximal distribution of the left anterior descending artery LV1, distal distribution of the left anterior descending artery LV2 and posterior wall of the left ventricle LV3 were: 81.3 +/- 11.5, 145.1 +/- 20.8 and 165.4 +/- 35.8 fmol/mg protein, respectively. Thus, the distribution of the beta-adrenoceptor densities was greatest in the apex of the left ventricle. The data suggest that there are regional differences in the beta-adrenoceptor densities among the areas of the heart and within the left ventricle. These differences may be related to functional differences.

Metabolic responses of rabbit corpus cavernosum tissue to various forms of stimulation.

The present study was designed to investigate the effect of various forms of stimulation on the levels of high energy phosphates (ATP + CP) in the rabbit corpora cavernosa. Prestimulation with the alpha agonist phenylephrine (200 microM) for five minutes caused a significant decrease in both ATP and Creatine phosphate (CP) when compared with control tissue. Field stimulation (64 Hz) of the precontracted tissue induced an immediate decrease in tension by approximately 50%. The level of ATP + CP after field stimulated-relaxation was not significantly different from that from the initial prestimulation. Field stimulation (FS) from basal tone (2 g) caused a contraction and a significant decrease in both ATP and CP. Phentolamine (10 microM) (alpha-adrenergic antagonist) induced a significant decrease in the 2 g basal tension and a significant increase in the intracellular concentrations of both ATP and CP from that of control levels. In summary, the contractile response to both neuronal and pharmacologic stimulation was similar to that of other smooth muscle, producing a decrease in high energy phosphates. Field stimulated relaxation did not change the level of high energy phosphates from that of prestimulated levels. Finally, our data indicates that in the presence of the alpha blocker phentolamine (10 microM), high energy phosphate levels (ATP + CP) increase significantly. This indicates that in the corpus cavernosum, there is significant basal tone that is linked to significant tonic alpha receptor stimulation and is maintained by a net consumption of ATP.