Biomedical subjects

Penelope A Longhurst

Publications and source records attributed to Penelope A Longhurst.

6 recordsLinked to original sources

PubMed2003

Functional response of bladder strips from streptozotocin diabetic rats depends on bladder mass.

PURPOSE: We investigated the relationship of bladder mass to responses to electrical field stimulation and adrenergic agonists in diabetic rat bladders. MATERIALS AND METHODS: Longitudinal strips were removed from the ventral and dorsal detrusor of age matched control, 2-month diabetic and sucrose drinking rats. Contractile responses to electrical field stimulation, KCl and phenylephrine, and relaxation in response to norepinephrine and isoproterenol were measured. RESULTS: Bladders from sucrose drinking and diabetic rats weighed significantly more than those of controls. Diabetic rats were divided into 2 groups with the bladder weighing less than or greater than 265 mg. Strips from small diabetic bladders were generally more responsive to field stimulation and norepinephrine than those from control or sucrose drinking rats. Conversely decreased function was especially apparent in dorsal strips from large diabetic bladders. Ventral strips were significantly more sensitive to the relaxant actions of norepinephrine and isoproterenol than dorsal strips. CONCLUSIONS: Our results suggest that the responsiveness of diabetic rat bladder to electrical field stimulation and adrenergic agonists is related to bladder mass, analogous to observations after partial outlet obstruction. Decreased function was particularly apparent in dorsal strips from diabetic rats with a large bladder.

Adrenergic alpha-Agonists↗

PubMed2003

Functional development of the rat urinary bladder after pre- or postpubertal castration.

Experiments were done to evaluate the role of sex hormones in the functional development of the rat urinary bladder. Rats were orchiectomized or ovariectomized at 30 (prepubertal) or 70 (postpubertal) days of age and bladders were removed 1 month later. An additional group of immature male and female rats was used in which the bladders were removed at 30 days of age. There were only minor differences in contractile responses of bladder strips from any group to electrical field stimulation, ATP, carbachol, or KCl compared to age-matched controls. There were no differences in responses of bladder strips from immature females or males to the adrenergic agonists, isoproterenol, norepinephrine, or methoxamine. Bladders from the pre- and postpubertally castrated rats and their controls relaxed fully in response to isoproterenol, but strips from prepubertally castrated rats relaxed significantly less in response to norepinephrine than those from other groups. Approximately one half of the bladder strips from prepubertally castrated rats failed to relax by at least 50% in response to norepinephrine; these same strips responded to methoxamine with exaggerated contractions. Our data indicate that the normal development of rat bladder alpha-adrenergic responsiveness is adversely altered by prepubertal castration. We postulate that this may result from an alteration in the relative expression of alpha(1)-adrenergic receptor subtypes.

Adenosine Triphosphate↗

PubMed2003

Downregulation of CYP2D16 by ACTH in the guinea pig adrenal cortex: time course, reversibility, and mechanism of action.

Studies were done to investigate the actions of ACTH on the expression of CYP2D16 in the guinea pig adrenal cortex. Guinea pigs were treated with ACTH for 1, 3, or 7 days. In addition, some animals received ACTH for 7 days and were then untreated for an additional 3 or 7 days to test for reversibility of ACTH actions. ACTH treatment caused a time-dependent decrease in the rates of adrenal microsomal bufuralol metabolism, a CYP2D-catalyzed reaction; hepatic bufuralol metabolism was unaffected by ACTH. Adrenal enzyme activity was significantly reduced by ACTH within 1 day and decreased by 80% after 7 days. Western blotting and in situ hybridization analyses revealed corresponding declines in adrenal CYP2D16 protein and mRNA concentrations. Nuclear runoff assays indicated that ACTH treatment inhibited CYP2D16 expression at the transcriptional level. Adrenal 17 alpha-hydroxylase activities were increased by ACTH treatment, but CYP17 protein concentrations were not affected. Following cessation of ACTH administration, the rates of adrenal bufuralol metabolism and CYP2D16 protein and mRNA concentrations returned to control levels within 7 days. The results demonstrate that ACTH has a relatively rapid and reversible effect to inhibit adrenal CYP2D16 transcription, thereby decreasing adrenal xenobiotic metabolism. Thus, the actions of ACTH on CYP2D16 expression are opposite to those on other adrenal p450 isozymes, indicating unique regulatory mechanisms.

Adrenal Cortex↗

PubMed2002

In vitro rat bladder function after neonatal estrogenization.

PURPOSE: Experiments were done to evaluate the functional effects of neonatal diethylstilbestrol (DES) treatment on bladder function in male and female Noble rats. MATERIALS AND METHODS: At 5 months after neonatal DES bladders were removed and weighed. Ventral and dorsal bladder strips were prepared to evaluate the effects of neonatal DES on contractile responses to electrical field stimulation, carbachol, adenosine triphosphate, phenylephrine and KCl. Relaxant responses to the catecholamines arterenol (norepinephrine), epinephrine and isoproterenol were also monitored. RESULTS: Neonatal DES resulted in significant increases in bladder mass in males and females. Contractile and relaxant responses were largely unchanged by neonatal DES treatment and the only change observed was a decreased response of ventral strips from male neonatal DES rats to 4 and 8 Hz. stimulation. Ventral strips from male control and neonatal DES rats responded to field stimulation and carbachol with significantly greater responses than dorsal strips and were more sensitive to the relaxant actions of norepinephrine and epinephrine. CONCLUSIONS: The data confirm that neonatal DES causes infravesical obstruction. However, in contrast to published reports of the effects of surgically induced mild outlet obstruction, neonatal DES treatment has little effect on in vitro bladder strip contractile or relaxant function. Thus, the neonatal DES treated rat does not seem to be a useful model in which to study the in vitro effects of partial outlet obstruction on the bladder.

Adenosine Triphosphate↗

PubMed2002

Relationship of mass of obstructed rat bladders and responsiveness to adrenergic stimulation.

PURPOSE: The effects of experimental partial bladder outlet obstruction on the bladder response to nerve stimulation and contractile agonists have been well characterized. Mildly obstructed bladders have small increases in mass and increased contractile responses to electrical field stimulation. More severely obstructed bladders become decompensated with large increases in mass and decreased functional responses. Little is known about relaxant mechanisms after obstruction. We investigated the relationship of the increase in rat bladder mass induced by outlet obstruction and responses to alpha and beta-adrenergic stimulation. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 3 groups, namely control, sham operated and obstructed. Surgical obstruction was done by tying a 2-zero silk ligature around the urethra. The ligature was placed around the urethra and removed in sham operated rats. At 2 and 6 weeks bladders from all groups were harvested, weighed and cut into strips. Contractile responses to electrical field stimulation and norepinephrine in the presence of propranolol were measured. Relaxant responses to norepinephrine and isoproterenol were measured after pre-contraction with KCl. RESULTS: All strips from control and sham operated rats relaxed completely in response to norepinephrine. Obstructed bladders that weighed 2 to 3-fold more than control or sham operated bladders also relaxed. In contrast, bladders that were 5 to 10-fold heavier failed to relax by at least 50% in response to norepinephrine, independent of duration of bladder outlet obstruction. These were called nonresponders. Two week nonresponders relaxed completely in response to isoproterenol, but 6-week nonresponders did not, suggesting that the duration of decompensation is important. All nonresponders relaxed in response to pinacidil (Sigma-Aldrich Corp., St. Louis, Missouri). Nonresponders tended to contract in response to norepinephrine in the presence of propranolol. Strips from the other rats were less responsive, suggesting an increase in alpha1-receptors with decompensation. Contractile responses to field stimulation were increased in obstructed strips that relaxed to norepinephrine, while responses of nonresponders were decreased compared with controls and sham operated rats. CONCLUSIONS: Severely obstructed bladders had an increase in mass and a decreased response to field stimulation, indicative of decompensation. This response was accompanied by decreased ability to relax to beta-agonists and an increased response to alpha-agonists. These changes were not seen in smaller, compensated bladders. Our findings suggest a change in detrusor alpha1 and beta-adrenergic receptor density. An increase in detrusor alpha-receptors may explain the clinical efficacy of alpha-blockers in alleviating irritative voiding symptoms in men with benign prostatic hyperplasia.

Adrenergic Fibers↗

PubMed2002

Regional differences in bladder enlargement and in vitro contractility after outlet obstruction in the rabbit.

PURPOSE: Bladder outlet obstruction leads to bladder enlargement and subsequent decreases in contractile function in vivo and in vitro. We determined whether there were regional differences in bladder wall properties and in vitro contractile responses after 2 weeks of bladder outlet obstruction. MATERIALS AND METHODS: Male rabbits underwent cystometry. The bladder was then filled to 40 ml. and the surface was marked with 2-zero silk knots placed approximately 1 cm. apart. The distance between the knots was measured at 20, 40 and 80 ml. The animals then underwent the creation of surgical obstruction. After 2 weeks the obstruction was removed. Cystometry and measurements were repeated and strips were obtained from defined dorsal and ventral areas. Contractile responses to electrical field stimulation, adenosine triphosphate, carbachol and KCl were determined and compared with strips from unobstructed controls. RESULTS: In vivo expansion during bladder filling occurred evenly throughout the bladder wall in controls and the contractile response to all stimuli was similar in ventral and dorsal strips. After 2 weeks of bladder outlet obstruction the upper dome expanded to a significantly higher degree than the lower bladder body. The response to all stimuli was significantly reduced after bladder outlet obstruction and there was a significantly decreased response to all stimuli in dorsal compared with ventral strips. Strips from the dorsal midline showed a relaxation response to electrical field stimulation at low frequencies, whereas all ventral strips contracted. CONCLUSIONS: Functional remodeling after bladder outlet obstruction is a process that does not occur to the same extent throughout the bladder. The obstructed bladder is an inhomogeneous organ with significant regional differences in mechanical and pharmacological properties.

Adenosine Triphosphate↗