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Biomedical subjects

P O Madsen

Publications and source records attributed to P O Madsen.

At least 19 recordsLinked to original sources
PubMed1998

Role of intracellular Ca2+ stores in smooth muscle of human penile erectile tissue.

OBJECTIVE: In human erectile tissue smooth muscle contraction and detumescence are highly dependent on an increase in cytosolic [Ca2+]. The Ca2+ influx can be derived from the extracellular space or from intracellular sarcoplasmic stores. The role of both pathways was evaluated in an organ bath study on human cavernosal strips. PATIENTS AND METHODS: The tissue was obtained from 12 patients with chronic erectile dysfunction. The effects of Ca2+-free solution, ryanodine, caffeine and of nifedipine on electrically and adrenergically induced contractions were evaluated. RESULTS: Following an incubation period of 10 min in Ca2+-free solution the electrically induced contraction was reduced to 20%, whereas the contraction induced by phenylephrine (PE) was only reduced to 64 +/- 6% (mean +/- SEM). Ryanodine inhibited the PE-contraction to 30 +/- 6% and the additional application of caffeine or nifedipine further reduced the contraction to 11% and 8%. CONCLUSION: The results give evidence for a role of intracellular Ca2+-stores in human cavernosal tissue. Whether the more marked effect of ryanodine in tissue from patients with erectile failure in comparison with similar experiments in rabbit cavernosal tissue might be a sign of an increased cavernosal contractility in these patients remains to be shown in future experiments with normal erectile tissue.

Animals↗
PubMed1998

Histamine release and contrast media-induced renal vasoconstriction.

RATIONALE AND OBJECTIVES: The authors' purpose was to investigate the role of histamine release causing renal vasoconstriction induced by application of contrast media, an important element in contrast medium-induced nephrotoxicity. MATERIALS AND METHODS: Isometric contractions in rabbit segmental renal arteries stimulated with KCl and increasing concentrations of the ionic contrast medium diatrizoate and the nonionic agents iomeprol and iodixanol were studied both with and without increasing concentrations of the histamine H1 and H2 blockers diphenhydramine and cimetidine. Histamine concentrations after contrast medium application were determined. RESULTS: Contrast-induced, dose-dependent, reversible renal artery contractions of 27%, 4.5%, and 5% of the control KCl contraction were found for diatrizoate, iodixanol, and iomeprol respectively. Those induced by the ionic contrast medium were statistically significantly higher (P < .01). Contractions were partially inhibited by diphenhydramine (49%) but not by cimetidine. Significant elevation of histamine concentrations (P < .05) was detected only after stimulation with diatrizoate but not with nonionic agents. CONCLUSION: Ionic contrast medium induces histamine release leading to renal vasoconstriction, which can be partly blocked by H1 blockers. Histamine has no effect on renal vasospasm induced by nonionic contrast media.

Animals↗
PubMed1998

Prevention of contrast medium-induced renal vasospasm by phosphodiesterase inhibition.

RATIONALE AND OBJECTIVES: This study investigated the involvement of cyclic adenosine monophosphate (cAMP) in contrast medium-induced renal vasomotor effects and the efficacy of selective phosphodiesterase (PDE) inhibitors influencing cAMP in preventing contrast medium-induced renal vasospasm. METHODS: Isometric contractions of rabbit renal artery rings were subjected to increasing concentrations of the ionic contrast medium sodium/meglumine diatrizoate (DIA) and the nonionic contrast media iopamidol (IOP) and iodixanol (IOD) and compared with a potassium chloride control. Subsequently increasing concentrations of the nonselective phosphodiesterase inhibitors theophylline and papaverine and the following selective phosphodiesterase inhibitors were applied: vinpocetine, trequinsin, zardaverine, rolipram, and dipyridamole (subtypes I-V) before restimulation of the arterial tissue with contrast medium. RESULTS: Diatrizoate, iopamidol, and iodixanol induced contractions up to 30%, 15%, and 3.5% of the potassium chloride control, respectively. All phosphodiesterase inhibitors markedly inhibited the contrast medium-induced contractions in a dose-dependent manner. The selective phosphodiesterase inhibitors rolipram and trequinsin attenuated these contractions significantly more (92% and 94%) than did zardaverine, dipyridamole, and vinpocetine, with an inhibitory potency of 37%, 41%, and 62%, respectively. CONCLUSIONS: Nonionic contrast media induced renal vasoconstriction less potently than ionic contrast media. Significant differences in the ability to prevent contrast medium-induced vasoconstriction were observed among the various phosphodiesterase subtypes studied. selective phosphodiesterase inhibition with inhibitor subtypes II and IV showed the most promising results in specifically preventing contrast medium-induced renal vasospasm.

Animals↗
PubMed1997

Comparative regulation of alpha1-adrenergic receptor mediated contraction in urogenitally derived smooth muscle. Effect of epidermal growth factor.

Contractility of smooth muscle within mammalian urogenital organ systems has an established role in physiological/pathophysiological functioning of the component structures. Our aim was to examine the direct effect of epidermal growth factor (EGF) on smooth muscle tone as well as its indirect effects in regulating alpha1-adrenoceptor-mediated contraction of the prostate, the vas deferens and renal arteries. Tissues were mounted isometrically, under controlled conditions, and changes in tension in response to treatment with phenylephrine (PE) with or without pretreatment with EGF were recorded on a physiological recorder via force transducers. In the rabbit prostate, EGF potentiated the magnitude of contraction to PE. The potentiation appeared to be dependent on cyclo-oxygenase products. In the human prostate, EGF potentiated the contractile response to PE. EGF had no effect on the PE-induced contraction of the rabbit renal artery and vas deferens. EGF alone did not alter smooth muscle tone in any of the above-mentioned tissues. The main finding of this study is the difference in the regulation by EGF of the alpha1-adrenoceptor-mediated response in smooth muscle of the prostate, from that by the vas deferens and renal artery. The reasons for this difference in response remain to be elucidated. This study may form the basis for further investigation into receptor transregulation and its relevance to symptomatic benign prostatic hyperplasia (BPH).

Animals↗
PubMed1997

Variable effects of iodinated contrast media on different rabbit arteries in vitro.

Vasoconstriction caused by iodinated contrast media (CM) has been considered specific for the renal artery only. We examined the vascular effect of CM in rabbit carotid, aorta, renal, iliac, mesenteric and celiac arteries and found that other arteries also respond with a contraction to CM. Isolated arterial rings were exposed to diatrizoate (high osmolar CM), iohexol (low osmolar CM) or glucose solution, and the isometric contraction response was expressed as percentage of an initial KCl control contraction. Diatrizoate evoked contractions of 82% (carotid), 63% (aorta), 30% (renal), 24% (iliac), 28% (mesenteric) and 18% (celiac), respectively. Iohexol caused contractions of 31% (carotid), 24% (aorta), 15% (renal) and 14% (iliac), whereas the mesenteric and celiac arteries were relaxed by iohexol. A high osmolar glucose solution elicited contractions of 78%, 77%, 11%, 27%, 3% and 5%, respectively, in the arteries. CM have contraction potency in arterial vasculature other than the renal artery.

Animals↗
PubMed1997

Attenuation of contrast material-induced renal artery vasoconstriction by nitric oxide donors.

RATIONALE AND OBJECTIVES: The authors studied the role of the endothelium and associated endothelial pathways in contrast material-induced renal vasoconstriction. MATERIALS AND METHODS: Isometric contractions in human and rabbit renal artery rings with intact and denuded endothelium were stimulated with phenylephrine and increasing concentrations of the ionic contrast material diatrizoate, the nonionic contrast materials iopamidol and iomeprol, and the dimeric contrast material iodixanol in a tissue perfusion bath. Rings with intact endothelium were incubated with endothelium-stimulating compounds such as the NO synthetase inhibitor Ng nitro-L-arginine methyl ester (L-NAME) to study the endothelium-mediated vasomotor regulation and the NO-liberating substances molsidomine (SIN-1) and nitroprusside (NPR) to study the endothelial-mediated vasorelaxation before being stimulated with contrast material. RESULTS: Contrast material-induced, dose-dependent, reversible renal artery contractions are dependent on the type of contrast material. No differences in the contractions were found between intact and denuded rings. L-NAME had no effect on contrast material-induced contractions. Contractions were inhibited by the NO donors SIN-1 and NPR. SIN-1 was the most potent inhibitor. CONCLUSION: Contrast material-induced renal vasoconstriction is endothelium-independent. Selective pharmacologic stimulation of the endothelium by NO donors, however, may still be useful in the prophylaxis of contrast material-induced renal vasoconstriction and, thus, potentially nephrotoxicity.

Animals↗
PubMed1997

Comparison of iodinated contrast media-induced renal vasoconstriction in human, rabbit, dog, and pig arteries.

RATIONALE AND OBJECTIVES: Contrast media (CM)-induced renal vasoconstriction is an important factor in the pathogenesis of CM-induced nephrotoxicity. The effects of ionic, high-osmolar CM sodium/meglumine diatrizoate and nonionic, low-osmolar CM iohexol and iopamidol were studied in rabbit, dog, and pig renal arteries and compared with human tissue in an organ bath. METHODS: Isometric contractions were induced by increasing concentrations of CM and high-osmolar glucose solution. RESULTS: Contrast media and glucose elicited contractions in human renal arteries of 32% (diatrizoate), 20% (iohexol), 30% (iopamidol), and 22% (glucose). Rabbit and dog renal arteries demonstrated contractions of 30% and 46% (diatrizoate), 15% and 23% (iohexol), 15% and 26% (iopamidol), and 11% and 40% (glucose), respectively, of the control. There was a vasorelaxing effect of all CM tested on pig renal artery. CONCLUSIONS: Responses in rabbit and dog renal arteries were similar to those in human renal arteries and could serve as models for investigating CM-induced renal vasoconstriction.

Animals↗
PubMed1997

Effect of contrast medium on corpus cavernosum smooth muscle.

RATIONALE AND OBJECTIVES: Changes in contractility of corpus cavernosum (CC) smooth muscle caused by radio contrast medium may result in misinterpretations of cavernosography used diagnostically in erectile dysfunction. METHODS: The authors investigated the direct effect of various contrast media on rabbit CC smooth muscle tissue strips in an in vitro model by adding contrast medium to the tissue in a perfusion bath and recording the resulting contractions. Glucose addition was used as control. RESULTS: Application of high-osmolar, ionic contrast medium diatrizoate-induced CC smooth muscle contractions of 57% of the control potassium chloride (124 mM) induced contractions. The low-osmolar (862 mOsm/kg) nonionic monomer contrast medium, iohexol, and the iso-osmolar (300 mOsm/kg) nonionic-dimer contrast medium, iodixanol, elicited contractions of 34% and 36% of the potassium chloride control contractions, respectively. High- and Iso-osmolar glucose solutions caused contractions of 51%, 38%, and 24% of the control, respectively. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) regulate CC smooth muscle contractions. These are influenced by different drugs including phosphodiesterases (PDEs), forskolin, and 3-morpholinsydnonimine hydrochloride (SIN-1). The nonspecific PDE inhibitors papaverine (0.1 mM) and theophylline (1 mM) reduced the contrast medium-induced contractions to 66% and 69%, respectively. The specific PDE inhibitor milrinone (0.1 mM) reduced the contractions to 69%; 0.1 mM forskolin and SIN-1 reduced the contractions to 34% and 41%, respectively. CONCLUSIONS: Contrast medium induces CC smooth muscle contractions, depending mainly on the osmolality of the solution. The contractions are reduced but not abolished by elevating the intracellular cAMP and cGMP concentrations. The clinical applications in cavernosography are discussed.

Animals↗
PubMed1996

Role of intracellular calcium stores in contrast medium-induced renal vasoconstriction.

RATIONALE AND OBJECTIVES: Renovascular smooth muscle contractility, an important factor in contrast media-induced nephrotoxicity, depends on intracellular Ca2+ concentration, which is composed of extracellular Ca2+ influx and intracellular Ca2+ release. These factors were investigated in contrast media-induced renal vasoconstriction in an in vitro model. METHODS: KCl-induced isometric contractions of rabbit renal artery were compared with contractions elicited by contrast media (diatrizoate, iohexol, iopamidol). Measurements were made after incubation with the Ca2+ channel blockers nifedipine, verapamil, and diltiazem to assess the role of extracellular Ca2+ influx and after ryanodine and thapsigargin to investigate the role of intracellular Ca2+ release. RESULTS: The Ca2+ channel blockers partially inhibited contractions induced by contrast media, while KCl-induced contractions were completely abolished. Ryanodine and thapsigargin also markedly inhibited contrast media-induced contractions. CONCLUSION: Ionic and nonionic contrast media induced quantitatively different renal vasocontractions. Ca2+ channel blockers inhibited this vasocontraction only slightly compared with intracellular Ca2+ release blockers.

Animals↗
PubMed1995

Ryanodine-sensitive intracellular Ca2+ stores in isolated rabbit penile erectile tissue.

Norepinephrine release from adrenergic nerve terminals leads to a rise in intracellular Ca2+, which promotes penile smooth muscle contraction and detumescence. Ca2+ sources are the extracellular space and sarcoplasmic Ca2+ stores. To elucidate the role of intracellular stores strips from rabbit erectile tissue were investigated in an organ bath study. Contractions were elicited by phenylephrine (PE) and electrical stimulation. Incubation in Ca(2+)-free solution as well as exposure to nifedipine did not abolish electrical or PE-induced contraction. Ryanodine (10(-5) mol/l), a functional blocker of sarcoplasmic Ca2+ channels, significantly reduced PE response. In the presence of caffeine (10(-3) mol/l) the effect was significantly enhanced. Addition of nifedipine nearly abolished the contraction. These results provide evidence for intracellular Ca2+ pools in cavernosal tissue and indicate that the alpha 1-adrenoceptor-induced contraction requires the opening of voltage-gated Ca2+ channels and the release of Ca2+ from intracellular stores.

Animals↗
PubMed1995

Transurethral resection versus incision of the prostate: a randomized, prospective study.

OBJECTIVES: To evaluate longer term effects of transurethral resection (TURP) and incision (TUIP) of the prostate in randomized patients. METHODS: In a randomized, prospective study, 120 patients with symptoms of bladder outlet obstruction caused by smaller benign prostates (estimated resectable weight less than 20 g) were assigned to TURP or TUIP. Patients were evaluated preoperatively and at intervals postoperatively as to urinary symptoms (Madsen's questionnaire), sexual function, and uroflowmetry. Overall evaluation of outcome of surgery was also assessed at follow-up visits. RESULTS: Fifty-six patients received a TURP and 61 a TUIP. Three patients refused to participate in the project after randomization, and 5 patients were lost to or excluded from follow-up. A group of 112 patients were obtainable for postoperative evaluation with a mean follow-up time of 34 months (1 to 82 months). Improvements in mean urinary peak flow rates were seen in both groups throughout the study period. The peak flow rates generally were higher (but not statistically so) in the TURP group. Postoperative irritative, obstructive, as well as total symptom scores decreased significantly at all follow-up visits after both TURP and TUIP (P < or = 0.034). Preoperatively and at all postoperative follow-up there was no statistically significant difference in irritative, obstructive, or total symptom scores between TURP and TUIP. The patients indicated an overall subjective improvement at all follow-ups in both groups, with no statistically significant difference between the treatment groups. Fifteen of 22 (68%) patients receiving TURP and 8 of 23 (35%) in the TUIP group who were sexually active before and after surgery developed postoperative retrograde ejaculation (P = 0.020). Postoperatively, 9 (16%) of the patients in the TURP and 14 (23%) in the TUIP group received further treatment for benign prostatic hyperplasia (BPH)-related infravesical obstruction. This difference was not statistically significant (P = 0.908). CONCLUSIONS: In small prostates TURP and TUIP were generally equally effective in relieving bladder outlet obstruction secondary to BPH. Most surgically treated BPH cases can be well managed by the incision technique, which is an underutilized procedure.

Adult↗
PubMed1995

Regulation of prostatic smooth muscle contractility by intracellular second messengers: implications for the conservative treatment of benign prostatic hyperplasia.

The increased sympathetic neurotransmission in benign prostatic hyperplasia (BPH) results in a alpha 1C-adrenoceptor-mediated increase in prostatic smooth muscle tone which seems to be responsible for the dynamic infravesical obstruction occurring in BPH. The prostatic smooth muscle contractions evoked by norepinephrine can be efficiently blocked by alpha 1-adrenoceptor blockers. Moreover, an impressive number of clinical trials illustrated the beneficial results of alpha 1-adrenoceptor blockers in the treatment of BPH. However, despite knowledge of alpha 1-adrenergic neurotransmission and the clinical application of its blockade by selective alpha 1-adrenoceptor antagonists, very little is known about the intracellular pathways involved in the regulation of prostatic smooth muscle contractility. To study the intracellular mechanism of the alpha 1C-adrenoceptor-induced prostatic smooth muscle contraction, the patch-clamp technique in the whole-cell configuration mode combined with the Fura-II fluorescence technique was used in human, enzymatically isolated smooth muscle cells obtained from patients undergoing transurethral resection of the prostate because of symptomatic BPH. Furthermore changes in prostatic smooth muscle contractility were registered in organ bath experiments. Application of the selective alpha 1-adrenoceptor agonist phenylephrine (PE) increased the L-type Ca(2+)-channel current (ICa) dose dependently from 8 up to 18.5 microA/cm2, simultaneously elevating the free cytoplasmic Ca2+ concentration ([Ca2+]i) up to 1.9 microM. Pretreating the myocytes with pertussis toxin, an exotoxin of Bordetella pertussis which inactivates GTP-binding proteins (G proteins) of the Gi and G(o) family by ADP ribosylation, reduced the PE-induced ICa stimulation by 71.5 +/- 5.6% (n = 21). Dialysis of the cytosol with the second messenger inositol-1,4,5-trisphosphate (IP3), which releases Ca2+ from intracellular non-mitochondrial, IP3-sensitive Ca2+ pools, imitated the PE-evoked responses. Pretreating the myocytes with the Ca(2+)-release blockers ryanodine (10-100 microM, n = 8), thapsigargin (0.1 microM, n = 11) or low-molecular weight heparin (n = 14) largely attenuated the PE-evoked responses. The experimental results suggest a coupling of alpha 1-adrenoceptors to phospholipase C-converting phosphoinositol-4,5-bisphosphate into diacylglycerol, an endogenous activator of the protein kinase C and IP3 which releases Ca2+ from intracellular stores stimulating ICa via Ca(2+)-calmodulin-dependent protein kinase induced phosphorylation of voltage-dependent Ca2+ channels. This knowledge could be of interest for conservative treatment in symptomatic BPH.

Calcium Channel Blockers↗
PubMed1995

[Long-term results of transurethral prostate incision (TUIP) and transurethral prostate resection (TURP). A prospective randomized study].

TUIP (transurethral incision of the prostate) or TURP (transurethral resection of the prostate) was performed in 120 patients to treat small-volume (< 20 g) benign prostatic hyperplasia in a prospective randomized study. The mean follow up was 43 months. Preoperatively and at regular follow-up visits obstructive and irritative symptom scores were obtained, sexual function was evaluated, and a uroflow study was performed. Both treatments achieved a marked improvement of symptoms. The obstructive, irritative and the total symptom scores did not differ significantly between TURP and TUIP. After 2-3 years the scores slowly increased in both groups. Subjective satisfaction rates averaged about 60% after more than 3 years and remained at this level. Initial significant differences in the peak flow rate in favour of TURP were no longer seen after more than 2 years. In smaller prostates TURP and TUIP are equally effective and since TUIP has fewer side effects and entails lower costs it appears to be an acceptable alternative to TURP.

Adult↗
PubMed1995

Contrast medium induced renal vasoconstriction, role of alpha receptors.

Standard imaging techniques for evaluation of renal and renovascular disease require the application of radiocontrast medium. The use of high osmolar, ionic radio contrast medium is however associated with adverse effects including acute renal insufficiency. Renal vasoconstriction seems to play an important role in the pathomechanism of this side effect. The cellular mechanisms however remain unsolved. Alpha 1-adrenoceptors and their subtypes are the crucial link between sympathetic stimulation and renal vasoconstriction. We investigated the role of alpha 1-receptors and the alpha 1A and alpha 1B subtypes in the renal artery and in sodium/meglumine diatrizoate induced renal artery smooth muscle contraction. Alpha 1-receptor induced rabbit renal artery contraction was produced by stimulation with the specific agonist phenylephrine which was antagonized dose-dependently and reversibly by the alpha 1-blockers prazosin, terazosin and YM 617. The alpha 1A-receptor was the prevalent receptor subtype in rabbit renal artery. This was identified by applying the specific alpha 1A-receptor antagonist 5-methylurapidil and the irreversible alpha 1B-receptor antagonist chloroethyllonidine. These two inhibited the PE induced contraction by 96% and 66%, respectively. Sodium/meglumine diatrizoate elicited renal artery contraction at 25% of the phenylephrine control. This contraction was not influenced by alpha 1-blockers indicating the absence of an alpha 1-receptor mediated process.

Adrenergic alpha-Agonists↗