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Biomedical subjects

C G Stief

Publications and source records attributed to C G Stief.

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

Comparison of the effects of various spasmolytic drugs on isolated human and porcine detrusor smooth muscle.

The spasmolytic activity of flavoxate (CAS 15301-69-6), anticholinergic agents oxybutynin (CAS 5633-20-5), and trospium chloride (CAS 10405-02-4), drugs commonly utilized in the therapy of hyperactive bladder, and phosphodiesterase (PDE) inhibitors papaverine (CAS 58-74-2) and vinpocetine (CAS 42971-09-5) on muscarinic contractions of detrusor smooth muscle strips isolated from human and porcine urinary bladder was studied in vitro using the organ bath technique. Trospium chloride was most effective in relaxing contractions elicited by muscarinic stimulation, while flavoxate was significantly less effective than all other drugs tested. The relaxing potency of oxybutynin was greater than those of PDE-inhibitors papaverine and vinpocetine but 3,000 fold less significant than those of trospium chloride. The effects of the individual drugs on muscarinic tension of both human and porcine detrusor muscle strips were nearly equal. The present results suggest that the pig might be an appropriate animal model for the study of effects of spasmolytic substances on the contractility of urinary bladder smooth muscle in vitro.

Animals↗
PubMed1997

Neurotransmission and the contraction and relaxation of penile erectile tissues.

The balance between contractant and relaxant factors controls the smooth muscle of the corpus cavernosum and determines the functional state of the penis (detumescence and flaccidity versus tumescence and erection). Noradrenaline contracts both the corpus cavernosum and penile vessels, mainly via stimulation of alpha(1)-adrenoceptors. Recent investigations have demonstrated the presence of several subtypes of alpha 1-adrenoceptors (alpha(1A), alpha(1B), and alpha(1D)) in the human corpus cavernosum and also that the noradrenaline-induced contraction in this tissue is probably mediated by two or, possibly, three receptor subtypes. Even if much of the available in vitro information suggests that endothelins (ETs) may be of importance for mechanisms of detumescence and flaccidity, the role of the peptides in the control of penile smooth-muscle tone in vivo is unclear, as is the question as to whether they can contribute to erectile dysfunction. For further evaluation of the clinical importance of ETs in penile physiology and pathophysiology, clinical studies on ET-receptor antagonists would be of interest. Neurogenic nitric oxide (NO) has been considered the most important factor for relaxation of penile vessels and the corpus cavernosum, but recent studies in mice lacking neurogenic NO synthase (NOS) have shown these animals to have normal erections. This focuses interest on the role of endothelial NOS and on other agents released from nerves or endothelium. For the time being the most effective means of inducing penile erection in men involves the intracavernous administration of prostaglandin E1 (PGE1). PGE1 may act partly by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP). Recent results obtained with the adenylate cyclase stimulator forskolin suggest that penile smooth-muscle relaxation leading to penile erection can be achieved through the cAMP pathway. Thus, transmitters and agents acting through this second-messenger system may significantly contribute to relaxation of penile smooth muscle and to erection.

Animals↗
PubMed1997

Signal transduction in cavernous smooth muscle.

Knowledge of intracellular signal propagation in smooth-muscle tone regulation is of major importance to the understanding of both the physiology of erection and the pathophysiology of erectile dysfunction and the development of new and selective pharmacological agents in the treatment of erectile dysfunction. Cavernous smooth-muscle tone depends heavily on the amount of intracellular free Ca2+. In the resting state the sarcoplasmic free Ca2+ amounts to about 120-270 nM, whereas in the extracellular fluid the Ca2+ level is in the range of 1.5-2 mM. Electromechanical and pharmacomechanical coupling induces an increase in the levels of free sarcoplasmic Ca2+ by a factor of 2-3 to 550-700 nM that triggers myosin phosphorylation and subsequent smooth muscle contraction. In this case, modulation of membrane-bound ion channels and regulation of the intracellular second-messenger system are attractive and feasible targets for pharmacological intervention. Besides the amount of free sarcoplasmic Ca2+, smooth-muscle tone is also modulated by the regulation of Ca2+ sensitivity ("Ca-sensitization") and Ca(2+)-independent contraction processes.

Animals↗
PubMed1997

Cyclic nucleotide phosphodiesterase in human cavernous smooth muscle.

Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are important second messengers in mediating relaxation of various smooth-muscle cells. This second-messenger pathway also appears to be essential for cavernous smooth-muscle relaxation on the basis of the assumption it would be of theoretical and clinical interest to determine the functional relevance of various phosphodiesterase (PDE) isoenzymes in human cavernous smooth-muscle This study was concentrated on characterizing PDE isoenzymes that exist in cavernous smooth muscle and evaluating the effect of selective PDE inhibitors on relaxation that is needed for the initiation of erection. Separation of PDE isoenzymes was performed using anion-exchange chromatography [diethylaminoethanol (DEAE)-Sepharose column], and a modification of the PDE-assay method proposed by Thompson and Lakey was used. The relaxation effect of PDE inhibitors was evaluated in an organ-bath study. Three different PDE isoenzymes have been shown in human cavernous smooth-muscle homogenate: cGMP-inhibited PDE (PDE III), cAMP-specific PDE (PDE IV), and cGMP-specific PDE (PDE V). All PDE inhibitors tested showed a relaxation effect on isolated human cavernous smooth-muscle, albeit with differing potency. Quazinone (a selective PDE III inhibitor) had potency at least equal to that of papaverine (a non-selective PDE inhibitor) and had a superior effect as compared with Rolipram (a selective PDE IV inhibitor) and zaprinast (a selective PDE V inhibitor). The present study provides the rationale and opens the possibility of using selective PDE inhibitors in the treatment of patients with erectile dysfunction.

Animals↗
PubMed1997

Computer-assisted interpretation of electromyograms of corpora cavernosa using fuzzy logic.

An electromyogram of the corpora cavernosa (CC-EMG) imparts information on the autonomic cavernous innervation and/or the cavernous smooth muscles. The CC-EMG is interpreted mainly by evaluation of signal patterns of higher activity. The time required for interpretation is reduced by the implementation of a computer-assisted diagnosis program with a Microsoft Windows user interface. The program offers four levels of diagnosis: on the first level, recordings can be edited; on the second and third levels, signal patterns can be searched or evaluated; and on the last level the final diagnosis is provided. The computer-assisted interpretation is based on digital measurement data. These data have been obtained through a 170.6-Hz sampling frequency and a quantization of 10 V/12 Bit of the amplified signal. The first task of this diagnosis program is to discover and extract signal patterns of higher activity from data stored on the hard disk of a personal computer (PC). For a mathematic description of these patterns the following features were defined: relative time position, relative reproducibility, part of normal phases, and part of whip phases. Syntactic pattern recognition was introduced to identify the characteristic signal forms. An evaluation of the patterns could be derived from these features using fuzzy logic. For a summary of the evaluated patterns the variable global normality was established. The global normality forms an important evaluation basis along with the global synchronism, which represents an investigator's first impression of a recording. The final diagnosis is completed using fuzzy logic. The program was tested by comparison of expert and computer diagnoses. A total of 30 records were independently evaluated by an expert team and the computer program. With reference to the four classified levels of diagnosis a correspondence of 70% could be found. Furthermore, the rate in each of the classified levels was higher than 50%. The discrimination between normal and abnormal evaluation was 80% for clinical routine. Our results show that a computer-assisted interpretation of the CC-EMG can be achieved using mathematically based software. Within the last 7 months this computer-assisted CC-EMG program proved to be of great help in routine diagnosis. Furthermore, it demonstrated results comparable with a blinded-expert interpretation. This approach should bring about dramatic improvements in the diagnosis of erectile dysfunction.

Electromyography↗
PubMed1997

[Dorsal ligation of the penile vein--prognostic factors and long-term outcome].

Poor longterm success has been reported for penile vein ligation the last few years. Therefore, we decided to re-investigate our group of 147 patients who were operated on between 1987 and 1996. All patients showed a negative response to intracavernous injection therapy at the time of diagnosis and revealed a maintenance flow > 15 ml/min, as well as a pathological venous flow with pharmacocavernosometry or pharmacocavernosography. These patients underwent ligation of all superficial dorsal veins and resection of the deep dorsal vein of the penis. An up-to-date record of the success of the operation was kept either by a renewed clinical visit or by a standardized telephone interview or questionnaire. A total of 126 patients were available here for long-term follow-up. We divided the findings into three groups: complete spontaneous erection, postoperative response to cavernous autoinjection therapy and no changes in erectile competency postoperatively. The short-term success rate for these groups after 1-3 months was an outcome of 31 (24.6%), 25 (19.8%) and 70 (55.6%) patients; 86% of the cases whose results deteriorated after the initial operation success rate had this happen within the first postoperative year (p < or = 0.001). Favorable prognostic factors were preoperative erectile dysfunction of < or = 7 years, a normal CC-EMG and a maintenance flow of < or = 45 ml/min. If all three parameters were present, the long-term success rate (spontaneous erection plus response to intracavernous injection) of 30% of all patients was found to rise to 67% in this selected group of patients (p < or = 0.001). This study reveals that long-term success for unselected patients undergoing penile venous surgery is disappointing; however, careful selection of patients by certain prognostic factors can improve long-term results.

Adult↗
PubMed1997

Long-term results following dorsal penile vein ligation in 126 patients with veno-occlusive dysfunction.

One hundred and forty-seven patients who had dorsal penile vein ligation (DPVL) between 1987 and 1996 were re-investigated either during clinical consultation or by standardised telephone interview respectively questionnaire. One hundred and twenty-six patients were available for long-term follow-up. Postoperative outcome was classified into complete spontaneous erection, postoperative response to pharmacotherapy or no satisfactory improvement. The short-term success after 1-3 months according to this classification was 31 (24.6%), 25 (19.8%) and 70 (55.6%). These results were found to have deteriorated on long-term observation; with only 14 (11.2%), 24 (19.0%) and 88 (69.8%) respectively. Positive prognostic factors were preoperative duration of erectile dysfunction of < or = 7 y, a normal CC-EMG and a maintenance flow of < or = 45 ml/min. With all three parameters present, longterm success (spontaneous erection plus responder to intracavernous injection) rose from 30 to 67% in this selected group (P < or = 0.001). Our study shows that long-term success for unselected patients undergoing DPVL is disappointing; however, careful patient selection significantly improves long-term results.

Electromyography↗
PubMed1997

Prognostic relevance of intracaval neoplastic extension for patients with renal cell cancer.

OBJECTIVE: To assess the diagnosis of vena caval thrombosis (VCT) in patients with renal cell carcinoma (RCC) as an independent indicator of prognostic importance and when combined with additional tumour characteristics in a controlled multivariate analysis. PATIENTS AND METHODS: The clinical course of 53 patients (41 men and 12 women, mean age 60 years, range 35-79) with RCC and VCT was compared with that of a control group of 47 patients (37 men and 10 women, mean age 57 years, range 32-76) with RCC but no neoplastic extension into the vena cava. RESULTS: With a follow-up of 1-154 months and a mean long-term survival of 32 and 35 months, respectively, for patients with and without VCT, neither the propagation of the tumour into the vena cava (P = 0.391) nor the cranial extension of the thrombosis (P = 0.158) were identified as having any prognostic value during univariate or multivariate statistical analysis. The presence of regional lymph node (P < 0.001) or distant metastases (P = 0.009) was an independent prognostic variable for patients with RCC, with a significant decrease in long-term survival (13 and 14 months for patients with lymph node and distant metastases, respectively). CONCLUSION: A radical surgical approach is essential as standard therapy for the treatment of patients with RCC and neoplastic extension into the vena cava. Because they have a significantly decreased life expectancy, asymptomatic patients with lymph node or distant metastases should be treated conservatively.

Adult↗
PubMed1997

Computer-assisted evaluation of the smooth-muscle electromyogram of the corpora cavernosa by fast Fourier transformation.

OBJECTIVE: The aim of our study was to investigate analogous and digital recording of corpus cavernosum EMGs (CC-EMGs) in normal men according to criteria that were recently agreed upon in an international consensus workshop. METHODS: CC-EMGs were analogously and digitally registered from 37 normal subjects. Power spectra in the frequency domain were determined via fast Fourier transformation (FFT). RESULTS: Thirty-one of men showed identical or at least very similar electrical activity patterns in the analogous and digital registration. Needle penetration artifacts (investigated in 18 subjects) were found in 17/18 CC-EMGs during the first 20 min. Power spectra show a maximum of power at a frequency of 0.3 Hz with more than 90% of the power located between 0 and 5 Hz. CONCLUSIONS: Registration of CC-EMGs in normal men resulted in interindividually reproducible recordings. Age hardly affected CC-EMGs. Computer-assisted evaluation by FFT after elimination of artifacts was feasible. Thus, interpretation of the CC-EMG signals by a computer-aided expert system seems to be promising for clinical routine, in particular with respect to an increase in objectivity and a decrease in time needed for interpretation.

Adolescent↗
PubMed1997

[Electromyograms in erectile dysfunction and computer-assisted interpretation].

The electromyogram of the corpora cavernosa (CC-EMG) provides information on the autonomic innervation and/or smooth musculature. The interpretation of the CC-EMG, usually by evaluating signal patterns of higher activity, is time-consuming. To improve this situation, a computer-aided diagnosis employing a Microsoft Windows user interface was developed. The computer-aided interpretation is based on digital measurement data obtained using a 170.6 Hz sampling frequency and quantization of 10 V/12 bits of the signal. The first task of the program is to extract signal patterns of higher activity from stored data. To describe these patterns in mathematical terms, the features "relative time position", "relative reproducibility", "portion of normal phases", and "portion of whip phases" are calculated. Characteristic signal forms (normal and whip phases) are identified by means of syntactic pattern recognition. Using fuzzy logic, the features are used to effect pattern evaluation. To summarize the evaluated patterns, the variable "global normality" has been established, and linked to the "global synchronicity" at a second fuzzy logic level, to produce the final diagnosis. Finally, 30 records were evaluated independently by a team of experts and by the computer program. In relation to four established diagnostic classes, a correspondence of 70% was found. Furthermore, the accuracy achieved in each of the individual classes was better than 50%. Discrimination between normal and abnormal evaluation, which is of particular interest, reached 80%.

Autonomic Nervous System↗
PubMed1997

[Pharmacological therapy in erectile dysfunction--current standards and new viewpoint].

Intracavernous pharmacotherapy of erectile dysfunction has been established for over 10 years, with prostaglandin E1 (PGE1) being the standard substance with the lowest rate of side effects. Recent investigations deal with the identification of intracellular mechanisms of smooth muscle relaxation in cavernous tissue as the most important aspect of penile erection. Nitric oxide and specific phosphodiesterase-isoenzymes seem to play a central role. This resulted in clinical studies with the intracavernous injected nitric oxide-donor linsidomine (SIN 1) and the orally given phosphodiesterase-inhibitor sildenafil. Furthermore new ways of pharmaco-application are tested, e.g. transdermal treatment with nitroglycerin, minoxidil or papaverine, as well as intraurethral injection of prostaglandin E1.

Alprostadil↗
PubMed1997

Surgery for metachronous solitary liver metastases of renal cell carcinoma.

PURPOSE: The postoperative outcome and survival of patients undergoing surgery for metachronous solitary liver metastases of renal cell carcinoma were evaluated. MATERIALS AND METHODS: Between 1983 and 1993, 17 patients with metachronous liver metastases of renal cell carcinoma underwent laparotomy for metastatic liver disease. All patients had undergone radical nephrectomy a mean of 3.6 years before the diagnosis of liver metastases. RESULTS: Surgical resection was feasible in 13 of 17 patients with right hemihepatectomy in 9 (3 multivisceral resections), wedge resection in 4 and ex situ (mobilization and eversion out of the abdomen) resection in 1. Stage R0 resection (complete removal, negative surgical margins with no macroscopic disease left behind) was possible in 11 of 13 cases (85%). In patients with metastatic liver tissue resection the mortality rate was 31% (4 of 13) with additional significant morbidity in another 2. Mean survival of patients with nonresectable disease was 4 months, which increased to 16 months after resection. CONCLUSIONS: Complete resection of metachronous liver metastases can be achieved in the majority of patients. However, significant morbidity and mortality as well as the limited prognosis even after R0 resection strongly suggest careful patient selection.

Adult↗
PubMed1997

Corpus cavernosum electromyography: technique and clinical implications.

Recently, corpus cavernosum EMG (CC-EMG) has been introduced into the diagnostic evaluation of erectile dysfunction. It has been demonstrated that CC-EMG may be a valuable tool in the evaluation of the integrity of the autonomic innervation of the corpus cavernosum. The interpretation and comparison of the recorded data still remains problematic due to a lack of standardization of recording procedures, technical equipment and of data analysis software. The assessment of recorded data was originally performed visually and nonquantitatively, however, more recently, computer-aided analysis of digitized measurements has proved to be more objective, less time-consuming and more reliable. Future efforts should be aimed at creating larger databases and differentiating between the various sources of lesions within the autonomic neural network of the corpus cavernosum.

Electromyography↗
PubMed1996

Effects of various phosphodiesterase-inhibitors, forskolin, and sodium nitroprusside on porcine detrusor smooth muscle tonic responses to muscarinergic stimulation and cyclic nucleotide levels in vitro.

The cyclic nucleotides cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are second messengers involved in the regulation of contractility in various smooth muscle organs including detrusor smooth muscle. They are synthesized by activation of adenylate and guanylate cyclases, respectively, and inactivated by phosphodiesterases (PDEs). In order to delineate the intracellular regulation of porcine detrusor contractility by cyclic nucleotides and phosphodiesterases, functional organ bath studies and determinations of intracellular cyclic nucleotide contents were performed after incubation of porcine detrusor strips with forskolin (adenylate cyclase activator), sodium nitroprusside (guanylate cyclase activator), and various phosphodiesterase-inhibitors. Significant relaxant responses were achieved only by forskolin, the nonspecific phosphodiesterase-inhibitor papaverine, and the phosphodiesterase 1-inhibitor vinpocetine (62.4 +/- 5.6%, 73 +/- 4.3%, and 53 +/- 7.9%, respectively). Sodium nitroprusside and the selective PDE-inhibitors milrinone, rolipram, zaprinast, and dipyridamole were significantly less efficacious (26.9 +/- 3.9%, 15.5 +/- 3.8%, 15.3 +/- 3.0%, 13 +/- 4.0%, and 13.2 +/- 2.1%, respectively). Forskolin, papaverine, and vinpocetine elevated intracellular cAMP concentrations (7.3-, 1.9-, and 1.7-fold increase at 100 microM, respectively), whereas the other substances failed to enhance cAMP levels. cGMP levels were only increased by sodium nitroprusside (7.8-fold). The adenylate cyclase-cAMP system seems to be the more important signal transduction system involved in the relaxation of carbachol induced smooth muscle tone of the porcine detrusor. The role of the guanylate cyclase-cGMP system is less clear. In addition, the calcium/calmodulin-stimulated PDE I seems to be of major functional importance in regulating cAMP hydrolysis in the porcine detrusor smooth muscle in vitro.

Adenylyl Cyclases↗
PubMed1996

The renal paracrine peptide system--possible urologic implications of urodilatin.

Cardiodilatin/atrial natriuretic peptide (CDD/ ANP) is a hormone system of great clinical importance. The prohormone CDD/ANP-1-126 is a peptide synthesized in the heart and cleaved during exocytosis into the circulating form CDD/ANP-99-126. Urodilatin (CDD/ ANP-95-126) is a homologue natriuretic peptide that differs from CDD/ANP-99-126 by four amino acids. Whereas CDD/ANP-99-126 circulates in blood plasma and is not excreted into the urine, urodilatin is detected only in urine. Urodilatin exerts its renal effects in a paracrine fashion. After its secretion from cells in the distal tubule, it interacts with luminally located receptors in the collecting duct, resulting in increased diuresis and natriuresis. Results suggest that urodilatin plays an important role in the physiologic regulation of fluid-balance and sodium homeostasis. Pharmacology studies reveal significant differences when urodilatin and CDD/ANP-99-126 are given intravenously, showing that stronger diuresis and natriuresis are induced by urodilatin as compared with those induced by CDD/ANP-99-126. Clinical studies indicate the prophylactic and therapeutic effect of urodilatin in patients suffering from acute renal failure following heart and liver transplantation. A significant reduction in requirements for hemodialysis/hemofiltration can be achieved using urodilatin. Postobstructive diuresis and natriuresis is probably due to a defective urinary concentrating mechanism and is usually resistant to treatment with antidiuretic hormone. The distal tubule and collecting duct have often been considered to be the site of altered sodium and water excretion following relief of obstruction. Since circulating CDD/ANP-99-126 levels are markedly elevated during obstruction and decrease upon relief of the obstruction, natriuretic peptides may play an important role in this clinical feature. On the basis of recent findings attributing an important role in sodium homeostasis to urodilatin in contrast to CDD/ANP-99-126, future studies have to clarify whether urodilatin, not CDD/ANP-99-126, might be responsible for the altered renal sodium excretion observed in postobstructive diuresis. In the past decade a considerable amount of research has led to the identification and characterization of hormones of the natriuretic peptide family [13]. These peptides are involved in the regulation of salt and water homeostasis. The prototype of the natriuretic hormones is cardiodilatin/atrial natriuretic peptide (CDD/ANP), or A-type natriuretic peptide. CDD/ANP is primarily produced in the heart [6]. It is synthesized as a precursor molecule, CDD/ ANP-1-126, in specific granules in atrial myoendocrine cells [15]. The prohormone, upon appropriate stimuli for release, is cleaved into the C-terminus CDD/ANP-99-126 and excreted into the circulation via exocytosis [16]. Further members of the natriuretic peptide family are brain natriuretic peptide (BNP, or B-type natriuretic peptide) [45] and C-type natriuretic peptide (CNP) [46]. All the members of this family share many common features, including tissue distribution of gene expression, biosynthetic pathways, and pharmacologic effects in target organs [13,26]. The main biologic effects of these hormones are natriuresis, diuresis, and vasodilation [5, 6, 14, 22], but these vary among the individual peptides. Natriuretic effects such as increased glomerular filtration, inhibition of aldosterone production, and secretion result from direct inhibition of sodium absorption in the collecting duct. Urodilatin (INN: Ularitide) is a member of the natriuretic peptide family, discovered in 1988 by Schulz-Knappe et al. [43]. This hormone is presumably synthesized in the kidney and exerts potential paracrine renal effects [17]. Results of clinical phase I-II trials suggest a potent therapeutic effect of urodilatin in the treatment of acute renal failure in patients following organ transplantation [4, 27, 33].

Acute Kidney Injury↗
PubMed1996

Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle. I. Identification and characterization.

Phosphodiesterases (PDEs) are key enzymes involved in the regulation of intracellular cyclic nucleotide metabolism. The aim of the present study was to identify and to characterize the PDE isoenzymes present in the human detrusor smooth muscle. Human detrusor PDE isoenzymes were separated by Q-Sepharose anion exchange and calmodulin-agarose affinity chromatography and characterized upon their kinetic characteristics and their sensitivity to allosteric modulators and inhibitors. All five presently known PDE isoenzyme families were identified: one high-affinity, low-Km calcium/calmodulin-stimulated PDE I with a slight preference for cGMP over cAMP, one cGMP-stimulated PDE II, one cGMP-inhibited PDE III, one cAMP-specific PDE IV and one cGMP-specific PDE IV. All five known PDE isoenzyme families exist in human detrusor smooth musculature. The kinetic characteristics, together with functional in vitro studies, suggest that the PDE I may be of importance in the intracellular regulation of the human detrusor smooth muscle tone.

Anion Exchange Resins↗
PubMed1996

Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle. II. Effect of various PDE inhibitors on smooth muscle tone and cyclic nucleotide levels in vitro.

Phosphodiesterases (PDEs) regulate intracellular cyclic nucleotide metabolism and, thus, contraction and relaxation of smooth musculature. The aim of the present study was to evaluate the functional effects of isoenzyme-selective inhibitors and their effects on cyclic nucleotide levels in the human detrusor smooth muscle. In addition, the functional relevance of the cAMP versus the cGMP pathways in the regulation of the detrusor smooth muscle tone was assessed. Relaxant responses to various PDE inhibitors, forskolin and sodium nitroprusside (SNP) were investigated in vitro using a standard organ bath setup. Cyclic nucleotide levels were measured after incubation with the same substances using cAMP and cGMP radioimmunoassays (RIAs). Significant relaxant responses were only induced by non-selective PDE inhibition, the PDE I inhibitor vinpocetine and the adenylate cyclase activator forskolin. Relaxant responses to these substances were paralleled by increases in cyclic nucleotide levels. Our data suggest that the cAMP pathway and calcium/calmodulin-stimulated PDE (PDE I) may be of functional importance in the regulation of the human detrusor smooth muscle tone in vitro.

Cyclic AMP↗