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Biomedical subjects

K Persson

Publications and source records attributed to K Persson.

At least 91 records · Page 5Linked to original sources
PubMed1998

Actual and perceived postural sway during balance specific and non-specific proprioceptive stimulation.

A group of patients with balance complaints (n = 16) was compared with a group of normal subjects (n = 17) by means of posturography, subjective assessments of balance, anxiety and unsteadiness when standing on a force platform with eyes closed. Postural instability was induced by vibratory stimulation of the calf muscles (20, 40, 60, 80 and 100 Hz). As a control condition, the arm (biceps) was stimulated at similar frequencies. In order to control for arousal, blood pressure and heart beat were assessed. Furthermore, questionnaire responses on psychological measures were collected. Results showed clear differences between the groups in terms of imbalance and self-reports. However, the 2 groups displayed similar increases of imbalance during calf stimulation and no increase during arm stimulation. Patients generally rated less increase of unsteadiness when the calf was stimulated than did the controls. No differences in arousal were found between the groups or within conditions. Results are discussed in terms of the proposed desynchrony between symptoms and complaints.

Adult↗
PubMed1998

High prevalence of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in patients with cardiovascular disease and in middle-aged blood donors.

Nested polymerase chain reaction (nPCR) demonstrated the presence of Chlamydia pneumoniae-specific DNA in peripheral blood mononuclear cells (PBMC). PBMC samples were obtained from 103 consecutive patients (62 male, 41 female) aged 22-85 years (mean, 64) admitted for coronary angiography because of suspected coronary heart disease and from 52 blood donors (43 male, 9 female) aged 40-64 years (mean, 49). Of the 101 evaluable patients, 60 (59%) were identified by nPCR assay as C. pneumoniae DNA carriers; C. pneumoniae-specific microimmunofluorescence (MIF) serology confirmed exposure to the bacterium in 57 (95%) of the 60 nPCR-positive patients. Among the 52 blood donors, the nPCR assay identified 24 (46%) C. pneumoniae DNA carriers, all of whom were positive by C. pneumoniae-specific serology. Thirty-two patients (32%) and 23 blood donors (44%) were MIF antibody-positive but repeatedly nPCR-negative; Bartonella henselae- or Bartonella quintana-specific antibodies were not detected among any of these subjects. In this study, C. pneumoniae DNA was common in PBMC of patients with coronary heart disease and in middle-aged blood donors.

Adult↗
PubMed1998

Introduction and clonal spread of penicillin- and trimethoprim/sulfamethoxazole-resistant Streptococcus pneumoniae, serotype 9V, in southern Sweden.

As part of an intervention project, all patients in Malmöhus county with a culture positive for penicillin-resistant pneumococci, MIC > or =0.5 mg/L (PRP), have been registered since January 1995. Nasopharyngeal specimens were obtained from family members and close contacts of identified carriers. Children were denied attendance at regular day-care until PRP-negative. In 1995 and 1996, PRP were isolated from 882 individuals, 364 of whom had clinical infection and the remaining of whom were asymptomatic carriers. In 49%, the PRP were of serogroup 9, with MIC of penicillin 0.5-2.0 mg/L and resistance to trimethoprim/sulfamethoxazole. Further analyses with serotyping and genetic fingerprinting suggested strongly that most of the isolates belonged to a single serotype 9V clone. Month by month, an apparently continuous spread appeared from one municipality to a neighboring one. In most communities, the serotype 9V PRP appeared and disappeared within a few months. The active procedures of the intervention project may have limited the spread of the clone in the county.

Child↗
PubMed1998

Limiting the spread of penicillin-resistant Streptococcus pneumoniae: experiences from the South Swedish Pneumococcal Intervention Project.

In an attempt to limit the spread of penicillin-resistant pneumococci (PRP), an intervention project was initiated in the Malmöhus County, southern Sweden in January 1995. The ongoing project combines traditional communicable disease control measures and actions aiming at reducing antibiotics consumption. All patients in the county with a nasopharyngeal culture positive for PRP with MIC of Penicillin G > or =0.5 mg/L are followed with nasopharyngeal cultures until PRP-negative. Nasopharyngeal cultures are obtained from family members and close contacts of the index cases. Preschool children carrying PRP are denied attendance at group day-care. From January 1995 to March 1997, 1,038 PRP-carriers (429 index cases and 609 contact cases) were identified. Children aged 1-6 years dominated (83%). Antibiotics sales decreased during the study period, and epidemiologic data indicate that the intervention may have limited the dissemination of PRP in the county, but further evaluation is needed.

Adolescent↗
PubMed1998

Biphasic response to bradykinin in isolated porcine iliac arteries is mediated by bradykinin B1 and B2 receptors.

Bradykinin-induced responses were studied in isolated porcine iliac arteries. Relaxation was endothelium dependent and seen at low concentrations (10(-10)-10(-8) M) of bradykinin. It was inhibited by the bradykinin B2-receptor antagonist icatibant (HOE-140) and by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine. Bradykinin-induced relaxation was significantly potentiated by the kininase I carboxypeptidase inhibitor mergepta (10(-6) M). Bradykinin (>10(-7) M) elicited contraction of preparations with or without endothelium. The contraction was abolished by indomethacin but was not affected by the thromboxane A2/prostaglandin H2-receptor antagonist SQ 29,548. Icatibant and the bradykinin B1-receptor antagonist desArg9[Leu8]bradykinin significantly decreased bradykinin-induced contraction regardless of endothelial function. The contraction also was decreased by treatment with mergepta. The bradykinin B1-receptor agonist desArg9-bradykinin contracted endothelium-denuded arterial strips. This contraction was significantly decreased by desArg9[Leu8]bradykinin but not by icatibant. The desArg9-bradykinin-induced contraction also was inhibited by the protein-synthesis inhibitor cycloheximide. Neither bradykinin-induced relaxation nor contraction was affected by the ACE inhibitors enalaprilat or cilazaprilat. In conclusion, bradykinin-induced relaxation of isolated porcine iliac arteries was mediated by endothelial bradykinin B2 receptors and mainly nitric oxide. Bradykinin-induced contraction was endothelium independent, indomethacin sensitive, and probably mediated by bradykinin B1 (inducible) and B2 receptors located in the vascular smooth-muscle layer. Kininase I carboxypeptidase, and not ACE, is the main enzyme responsible for bradykinin degradation in these vessels.

3-Mercaptopropionic Acid↗
PubMed1998

Effects of polyamine synthesis inhibition on polyamines, growth and mechanical properties in hypertrophic rat urinary bladder.

The polyamines putrescine, spermidine and spermine, are ubiquitous intracellular metabolites associated with growth and protein synthesis. In this study effects of polyamine synthesis inhibition on bladder growth, polyamine levels and mechanical properties were investigated in rat urinary bladder subjected to partial outflow obstruction that causes bladder hypertrophy. The S-adenosyl methionine decarboxylase inhibitor CGP-48664 (5 and 20 mg kg-1) was administered alone or in combination with the ornithine decarboxylase inhibitor DFMO (500 mg kg-1), starting one day before creation of partial outflow obstruction and then daily for 7 days. The bladder muscle level of putrescine was increased 38 times and that of spermine reduced by 4 times while spermidine was unchanged after treatment with CGP-48664 (20 mg kg-1). The increase in putrescine was abolished in animals receiving CGP-48664 in combination with DFMO. Treatment with polyamine synthesis inhibitors could not prevent or reduce the hypertrophy of the bladder as judged by bladder wet weight and protein contents. The effects on polyamine quantities were not associated with changes in Ca(2+)-force relationship or in agonist and electrically stimulated force. In summary, treatment of rats with polyamine synthesis inhibitors resulted in changes in polyamine levels in the growing urinary bladder but did not affect growth or mechanical properties.

Adenosylmethionine Decarboxylase↗
PubMed1998

Analysis of the humoral immune response to Chlamydia outer membrane protein 2.

The humoral immune response to Chlamydia outer membrane protein 2 (Omp2) was studied. Omp2 is a highly genus-conserved structural protein of all Chlamydia species, containing a variable N-terminal fragment. To analyze where the immunogenic parts were localized, seven highly purified truncated fusion proteins constituting different regions of the protein were produced (Chlamydia pneumoniae-Omp2aa23-aa93, Chlamydia psittaci-Omp2aa23-aa94, and Chlamydia trachomatis-Omp2aa23-aa84, aa87-aa547, aa23-aa182, aa167-aa434, aa420-aa547). By an enzyme-linked immunosorbent assay with serologically defined patient sera, Omp2 was found to be a major immunogen of both C. pneumoniae and C. trachomatis infections (P < 0.0001). The humoral immune responses were not confined to any particular region of the Omp2 protein, and no species-specific anti-Omp2 immunoglobulins were detected.

Antibodies, Bacterial↗
PubMed1998

Nitrergic and cholinergic innervation of the rat lower urinary tract after pelvic ganglionectomy.

The possible coexistence of nitric oxide (NO) and acetylcholine in the rat major pelvic ganglion (MPG) was examined by double immunohistochemistry using antisera raised against NO synthase (NOS) and choline acetyltransferase (ChAT). The smooth muscle responses of the isolated bladder and urethra were recorded after bilateral cryoganglionectomy of the MPG, focusing on the possible development of denervation supersensitivity. In the MPG, NOS immunoreactivity (ir) was seen in a large number of cell bodies, but it was not as abundant as ChAT-ir cell bodies. Double immunolabeling showed that all NOS-ir cell bodies also displayed ChAT-ir. In ganglionectomized bladders, the electrical field stimulation (EFS)-evoked contractile response was markedly reduced. When compared with control bladders, detrusor strips from ganglionectomized rats were more sensitive to carbachol as revealed by a lower negative logarithm of the drug concentration eliciting 50% relaxation (6.5 +/- 0.04 vs. 5.9 +/- 0.07). In the urethra, the NO-mediated relaxant response to EFS was practically abolished by ganglionectomy, whereas no difference was found in sensitivity to 3-morpholinosydnonimine hydrochloride (SIN-1). SIN-1 produced an equal increase in tissue levels of guanosine 3',5'-cyclic monophosphate in urethral preparations from control and ganglionectomized rats. The results suggest that the NOS-ir nerves that mediate inhibition of rat urethral smooth muscle tone originate from the MPG and contain ChAT. No denervation supersensitivity to nitrergic stimulation was observed in the urethra after ganglionectomy.

Acetylcholine↗
PubMed1998

Spinal and peripheral mechanisms contributing to hyperactive voiding in spontaneously hypertensive rats.

The influence of noradrenergic mechanisms involved in micturition in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was investigated using continuous cystometry in in vivo and in vitro studies on isolated bladder and urethral tissues. Compared with WKY rats, SHR had a significantly lower bladder capacity (SHR: 0.7 +/- 0. 05 ml; WKY rats: 1.3 +/- 0.06 ml; P < 0.001), micturition volume (SHR: 0.4 +/- 0.04 ml, WKY rats: 1.2 +/- 0.05 ml; P < 0.001), and an increased amplitude of nonvoiding (unstable) bladder contractions. The effects of intrathecal and intra-arterial doxazosin on cystometric parameters were more pronounced in SHR than in WKY rats. There was a marked reduction in nonvoiding contractions after intrathecal (but not intra-arterial) doxazosin in SHR. Norepinephrine (0.1 microM-1 mM) failed to evoke contractions in bladder strips from WKY rats, in contrast to a weak contractile response in SHR. The response to electrical field stimulation was significantly less in bladder strips from SHR than from WKY rats. In WKY rats, norepinephrine produced concentration-dependent inhibition (87 +/- 5%, n = 6) of nerve-evoked bladder contractions. Almost no inhibition (11 +/- 8%, n = 6) was found in SHR. Alterations in bladder function of SHR appear to be associated with changes in the noradrenergic control of the micturition reflex, in addition to an increased smooth muscle and decreased neuronal responsiveness to norepinephrine. The marked reduction in nonvoiding contractions after intrathecal doxazosin suggests that the bladder hyperactivity in SHR has at least part of its origin in supraspinal and/or spinal structures.

Animals↗
PubMed1997

Capsaicin-induced bladder overactivity and nociceptive behaviour in conscious rats: involvement of spinal nitric oxide.

To investigate the role of nitric oxide (NO) in spinal regulation of lower urinary tract function and bladder nociceptive behaviour, cystometry was performed in conscious rats. The effects of intra-arterial and intrathecal administration of the NO synthase (NOS)-inhibitor, L-NG-nitroarginine methyl ester (L-NAME), were studied on volume- and capsaicin-induced micturitions. The incidence of nociceptive behaviour after intravesical capsaicin was investigated in the absence and presence of L-NAME. Intrathecal L-NAME (0.5 mg) had no effect on the normal, volume-induced micturition. Intravesical capsaicin (30 microM) increased the micturition pressure (p < 0.01), the basal pressure (p < 0.01) and decreased the bladder capacity (p < 0.01) and the micturition volume (p < 0.01). Administration of L-NAME intrathecally (0.5 mg) or intra-arterially (25 mg/kg) had no effects on the capsaicin-induced bladder activity. During capsaicin-infusion, the rats showed signs of distress such as licking and head-turning directed toward the abdomen. This nociceptive behaviour was shown during 31 +/- 3% (n = 6) of the observation period. The capsaicin-induced nociceptive behaviour was markedly reduced by intrathecal and to a less extent by intra-arterial, administration of L-NAME. The percentage time spent licking and head-turning was reduced to 11 +/- 2%, n = 6 (p < 0.001) and 18 +/- 3%, n = 6 (p < 0.05) in rats treated with intrathecal and intra-arterial L-NAME, respectively. The results suggest that NO is not involved in the spinal regulation of the volume- or capsaicin-induced micturition. In contrast, the nociceptive behaviour evoked by intravesical capsaicin seems to involve spinal NO.

Administration, Intravesical↗
PubMed1997

Polyamines regulate both transcription and translation of the gene encoding ornithine decarboxylase antizyme in mouse.

The degradation of ornithine decarboxylase (ODC) is mediated by antizyme, a protein regulated by the end-products of ODC activity, the polyamines. High levels of polyamines induce a +1 ribosomal frameshift in the translation of the rat antizyme message leading to the expression of a full-length protein. We have studied whether the regulation of antizyme expression occurs only at the level of translation or whether polyamine levels also affect the transcription of the antizyme gene. Thus, we have cloned and sequenced the mouse homologues of the rat ODC-antizyme gene and cDNA. Northern blot analysis shows that although high concentrations of polyamines do not affect the steady-state levels of antizyme message in L1210 leukemia cells, polyamine depletion using 2-(difluoromethyl)ornithine [Orn(F2Me)] leads to a marked decrease in mRNA levels. Results of transient transfections of luciferase-reporter-gene constructs driven by antizyme promoter fragments in untreated and Orn(F2Me)-treated Balb/C 3T3 cells indicate that the transcription of the antizyme gene is altered upon polyamine depletion. The amount of antizyme protein on Western blots was also altered by polyamine depletion and addition, and the polysomal distribution of antizyme message suggests a general translational increase of the message when polyamine concentrations are high. These results indicate a role for polyamines in the transcriptional and translational regulation of ornithine decarboxylase antizyme.

Animals↗
PubMed1997

Fractional factorial design optimization of the separation of pilocarpine and its degradation products by capillary electrophoresis.

The separation of pilocarpine and its degradation products by micellar electrokinetic capillary chromatography (MECC) has been optimized by using fractional factorial design of the experiments. Critical parameters were identified in a screening design, and an optimization design was used to optimize the separation. The optimal separation method was based on a borate buffer with sodium dodecyl sulfate (SDS). It is concluded that by using fractional factorial design it is possible to improve the separation of pilocarpine, its trans epimer, isopilocarpine and their hydrolysis products, pilocarpic acid and isopilocarpic acid.

Electrophoresis, Capillary↗
PubMed1997

Neurotransmitter release evoked by alpha-latrotoxin in the smooth muscle of the female pig urethra.

Neuronal regulation of smooth muscle tone in the female pig urethra has mainly been studied in vitro using electrical field stimulation (EFS) of nerves. Excitatory control is considered to be exerted by released noradrenaline, whereas inhibitory control is non-adrenergic non-cholinergic (NANC), and mediated by nitric oxide (NO), and an as yet unidentified agent. We investigated the functional and morphological effects of alpha-latrotoxin (alphaLTX), a spider neurotoxin believed to cause massive release of vesicle-stored neurotransmitters, on spontaneously developed urethral smooth muscle tone. The effects were compared to those of EFS and high potassium. In the presence of the NO-synthesis inhibitor N(omega)-nitro-L-arginine (L-NOARG: 0.3 mM) both alphaLTX and EFS evoked contractions. After treatment with scopolamine and phentolamine, no contraction was observed, and under these conditions alphaLTX and EFS induced relaxation. At low frequencies (<12 Hz), the EFS-induced relaxations were rapid, whereas at higher frequencies (>12 Hz), they were biphasic, consisting of a rapid first phase followed by a more long-lasting second phase. L-NOARG abolished the relaxations at low frequencies, as well as the first phase of the biphasic relaxation. The second phase was not affected by treatment with L-NOARG, but 0.1 microM omega-conotoxin GVIA, blocker of N-type voltage-operated calcium- channels (VOCCs), markedly reduced or abolished the response. In the presence of L-NOARG or omega-conotoxin GVIA, the alphaLTX-induced relaxation was significantly decreased, and the combination of L-NOARG and omega-conotoxin GVIA further reduced or abolished the relaxation. In preparations-treated with tetrodotoxin or scorpion venom, believed to inactivate nerves by acting on sodium channels, alphaLTX and EFS had no effects. alphaLTX-induced relaxation was not associated with changes in cyclic GMP or cyclic AMP content. High (80 mM) potassium solution induced a triphasic response of the preparation. A transient relaxation was followed by a restoration of tone, and then by a persistent relaxation. The persistent relaxation was slightly reduced by scorpion venom or L-NOARG, but reduced by 50% by a combination of L-NOARG and omega-conotoxin GVIA. Ultrastructural analysis of the urethral circular smooth muscle layer revealed a moderate amount of nerve profiles supplying the smooth muscle. In control preparations, the nerve profiles contained both small synaptic vesicles and large dense core vesicles. alphaLTX caused a major loss of both types of vesicle. The present data suggest that alphaLTX has the ability to release not only adrenergic and cholinergic transmitters, but also NANC mediators of relaxation, including NO, from nerve terminals in the urethra.

Acetylcholine↗
PubMed1997

Effects of the K+ channel opener, ZD6169, on volume and PGE2-stimulated bladder activity in conscious rats.

PURPOSE: To investigate the effects of the new K(ATP) channel opener, ZD6169, shown to have an in vivo selectivity for the bladder, on bladder activity in rats. MATERIALS AND METHODS: ZD6169 was given intra-arterially (i.a., 0.1 and 1 mg./kg.) or orally (3 mg./kg.) to conscious Sprague-Dawley rats undergoing continuous cystometry. Investigations were also performed before and after stimulation of bladder activity by intravesical prostaglandin (PG) E2. RESULTS: Intra-arterial ZD6169 increased residual volume, but caused no changes in other cystometric parameters. In rats receiving oral ZD6169, cystometric parameters were compared (every hour up to five hours) to those recorded in rats receiving oral vehicle. No differences were found, except in threshold pressure, which was significantly increased. Intravesical PGE2 20 microM increased micturition and basal pressures, and decreased bladder capacity and micturition volume. ZD6169 1 mg./kg., given i.a., reduced or completely prevented the activity induced by intravesical PGE2. Three hours after orally administered ZD6169 (3 mg./kg.), intravesical PGE2 20 microM had no effect. Three hours after oral administration of vehicle, the effects of PGE2 were attenuated, but still statistically significant. CONCLUSIONS: ZD6169, given i.a. or orally, increased threshold pressure, but had otherwise little effect on volume-induced micturition. However, the drug markedly reduced or prevented PGE2-induced bladder activity when given i.a.; it was also effective when given orally. If ZD6169 has inhibiting effects on bladder contraction in man without any cardiovascular actions, the drug may represent a novel, promising way of treating bladder overactivity.

Administration, Intravesical↗
PubMed1997

Morphological and functional evidence against a sensory and sympathetic origin of nitric oxide synthase-containing nerves in the rat lower urinary tract.

To establish which type of nerves (parasympathetic, sympathetic or sensory) produce nitric oxide in the rat lower urinary tract, chemical denervation of primary afferents and sympathetic nerves was carried out by systemic treatment with capsaicin and 6-hydroxydopamine, respectively, followed by identification of neuronal nitric oxide synthase immunoreactivity. Functional in vitro studies were also performed to examine whether the synthesis and release of nitric oxide was affected following treatment with the respective neurotoxins. Nerve fibres immunoreactive for substance P and calcitonin gene-related peptide were found in control tissue, but could not be detected following capsaicin treatment. In comparison, nitric oxide synthase-immunoreactive fibres appeared to be unaffected by capsaicin treatment. Administration of 6-hydroxydopamine resulted in a complete disappearance of tyrosine hydroxylase-immunoreactive nerves, whereas nitric oxide synthase-containing nerve fibres did not appear to be affected by the treatment. In ultrastructural studies, nitric oxide synthase immunoreactivity, as studied by colloidal gold particles, was found in the axoplasm and not in association with intraneuronal structures or synaptic vesicles. Gold particles representing substance P immunoreactivity were seen as clusters associated with large granular vesicles. In consecutive sections of nerve fibres, substance P and nitric oxide synthase were not found in the same axon profile. In functional studies on urethral tissue, application of capsaicin (1 microM) produced a long-lasting relaxation. The nitric oxide synthase inhibitor NG-nitro-L-arginine (0.1 mM) had no effect on this response. Systemic treatment with capsaicin or 6-hydroxydopamine had no effect on nerve-evoked, nitric oxide-mediated relaxations. The data suggest that nitric oxide synthase-containing nerves in the rat lower urinary tract do not belong to nerve populations sensitive to either the sympathetic neurotoxin, 6-hydroxydopamine, or the sensory neurotoxin, capsaicin.

Acetylcholinesterase↗
PubMed1997

Carbon monoxide-induced relaxation and distribution of haem oxygenase isoenzymes in the pig urethra and lower oesophagogastric junction.

1. The distribution of the carbon monoxide (CO) producing enzymes haem oxygenase (HO)-1 and -2 was studied by immunohistochemistry in the pig's lower urinary tract, including bladder extramural arteries, and the oesophagogastric junction (OGJ). In isolated smooth muscle from the urethra and the OGJ, the mechanisms for CO-induced relaxations were characterized by measurement of cyclic nucleotide levels and by responses to the guanylate cyclase inhibitor methylene blue and some K+ channel inhibitors. 2. HO-2 immunoreactivity was observed in coarse nerve trunks within the smooth muscle of the urethra and OGJ, and in nerve cell bodies of the enteric plexuses of the OGJ. Furthermore, the vascular endothelium of the intramural vessels of the urethra, bladder and OGJ, and the extramural vessels of the bladder, displayed HO-2 immunoreactivity. Two different antisera against HO-1 were used, but only one displayed immunoreactivity in neuronal structures. HO-1 immunoreactivity, as displayed by this antiserum, was seen in nerve cells, coarse nerve trunks and varicose nerve fibres in the smooth muscle of the urethra and OGJ. Some HO-2 and/or HO-1 (as displayed by both HO-1 antisera) immunoreactive cells with a non-neuronal appearance were observed within the smooth muscle of the OGJ, bladder and urethra. 3. In the urethral preparations, exogenously applied CO (72 microM) evoked a relaxation amounting to 76 +/- 6%. The relaxation was associated with an increase in cyclic GMP, but not cyclic AMP, content. CO-evoked relaxations were not significantly reduced by treatment with methylene blue, or by inhibitors of voltage-dependent (4-aminopyridine), high (iberiotoxin, charybdotoxin) and low (apamin) conductance Ca(2+)-activated, and ATP-sensitive (glibenclamide) K+ channels. Bladder strips, and ring preparations from the extramural arteries of the bladder, did not respond to exogenously administered CO (12-72 microM). 4. In the OGJ, exogenously applied CO evoked a relaxation of 86 +/- 6%, which was associated with an increase in cyclic GMP, but not cyclic AMP, content. Treatment with 30 microM methylene blue raised the spontaneously developed muscle tone, and reduced the maximum relaxation evoked by CO to 33 +/- 9%. Addition of 4-aminopyridine, apamin, glibenclamide, iberiotoxin, charybdotoxin or glibenclamide had no effect on the relaxations. 4-aminopyridine (0.1-1 mM), iberiotoxin (0.1 microM) and charybdotoxin (0.1 microM) increased the spontaneously developed tone, and a combination of charybdotoxin and apamin reduced CO-induced (24 microM CO) relaxations. 5. The present findings demonstrate the presence of HO in both neuronal and non-neuronal cells in the pig OGJ and lower urinary tract. CO produces relaxation of the smooth muscle in the OGJ and urethra, associated with a small increase in cyclic GMP concentration in both regions. Relaxations evoked by CO in the urethra do not seem to involve voltage-dependent, low and high conductance, or ATP-dependent K+ channels. However, in the OGJ relaxations evoked by CO can be attenuated by methylene blue and a combination of charybdotoxin and apamin.

Animals↗
PubMed1997

Characterization of angiotensin II formation in human isolated bladder by selective inhibitors of ACE and human chymase: a functional and biochemical study.

1. Functional recordings of smooth muscle tension and biochemical experiments on membrane fractions were performed to characterize angiotensin II (AII) formation in human isolated bladder smooth muscle. 2. A novel human chymase inhibitor CH 5450 (Z-Ile-Glu-Pro-Phe-CO2Me) and a recently developed human chymase substrate Pro11-,D-Ala12)-angiotensin I, claimed to be resistant to angiotensin converting enzyme (ACE) and carboxypeptidase, were used. 3. Angiotensin I (AI) (0.3 microM) induced a contractile response amounting to 58 +/- 5% (n=12) of the initial K+ (124 mM)-induced contractions. This response was reduced to 36 +/- 3% (n=8) by the ACE-inhibitor enalaprilat (10 microM), while pretreatment with soybean trypsin inhibitor (STI 200 microg ml(-1)) or CH 5450 (10 microM) had no effect. However, the combination of enalaprilat and STI reduced the AI-induced contractions to 19 +/- 5% (n=6), and the combination of enalaprilat and CH 5450 caused an almost complete inhibition of the AI-induced contractions to 1+/-1% (n=6). 4. The substrate (Pro11-,D-Ala12)-AI (3 microM) produced contractions which amounted to 57 +/- 4% (n=13) of the initial K+ (124 mM) contractions. These contractions were not affected by enalaprilat (10 microM). On the other hand, STI (200 microg ml(-1)) and CH 5450 (10 microM) added separately, depressed the (Pro11-,D-Ala12)-AI-induced contractions to 34 +/- 5% (n=6) and 24 +/- 4% (n=6), respectively. The combination of enalaprilat and STI or enalaprilat and CH 5450 did not produce any further inhibition. 5. Experiments with detrusor membrane fractions incubated with AI (50 microM) were performed. In the presence of enalaprilat (100 microM), carboxypeptidase inhibitor CPI (10 microg ml(-1)) and aprotinin (15 microM), CH 5450 (10 nM-1 microM) caused a concentration-dependent inhibition of AII formation. 6. The results confirm that AII is a potent contractile agent in the human isolated detrusor muscle. They also indicate that the serine protease responsible for AII formation in the human bladder in vitro is human chymase or an enzyme similar to human chymase.

Aged↗