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Biomedical subjects

H Hedlund

Publications and source records attributed to H Hedlund.

At least 73 records · Page 4Linked to original sources
PubMed1989

The action of pinacidil in the isolated human bladder.

The need for effective symptomatic treatment of patients with detrusor hyperactivity is widely recognized. In search of new principles of decreasing bladder contraction we have studied the effects of pinacidil on the isolated human bladder. Pinacidil is a recently developed antihypertensive agent classified as a K+ channel opener, and is believed to depress smooth muscle activity by this action. Pinacidil concentration-dependently depressed contractions elicited by carbachol, low concentrations of K+ (less than 60 mM) and electrical stimulation. In addition it caused a concentration-related increase in the efflux of 86Rb from preloaded detrusor cells. The effects on 86Rb efflux could be inhibited by tetraethylammonium chloride and procaine, but not by apamin, agents known to block K+-channels. The results support the view that part of the pinacidil effect on the human bladder is caused by an opening of K+-channels, efflux of K+ and subsequent hyperpolarization of the detrusor cells. Clinical testing of this new therapeutic principle for treatment of bladder hyperactivity seems justified.

Antihypertensive Agents↗
PubMed1989

Effect of atropine and terbutaline on motor activity of the continent caecal reservoir for urine.

The effects of muscarinic receptor blockade (atropine) and of beta-adrenoceptor stimulation (terbutaline) on the motor activity of the continent caecal reservoir for urine were studied in 12 patients during continuous filling of the reservoir. Basal pressure was low at high level filling, but pressure waves with amplitudes of 40 to 50 cm H2O occurred every other minute. The reservoir's functional adaptation, revealed as a diminished amplitude of pressure waves and evident soon after its construction, remained stable at long-term follow-up. Subcutaneously injected atropine or terbutaline did not influence the basal pressure but increased the volume at which the first pressure wave appeared and decreased the wave amplitude and frequency at high filling levels. Intra-reservoir instillation of these drugs did not alter the dynamic behaviour of the reservoir. In selected patients, orally administered anticholinergic drugs or beta 2-adrenoceptor agonists may be useful in the management of hyperactivity in a colonic segment used as a continent reservoir or bladder substitute.

Adult↗
PubMed1989

Influence of age, fat cell weight, and obesity on O2 consumption of human adipose tissue.

The oxygen consumption of human adipose tissue (AT) was determined in 53 adults, lean and obese, and in nine lean boys. The oxygen consumption was positively related to fat cell weight and negatively to age and degree of obesity. Men and women did not differ with respect to oxygen consumption of AT. The positive relationship between oxygen consumption per cell and fat cell size was also demonstrated in size-separated cells from the same donors. Expressed per cell the oxygen consumption was higher in fat cells from obese than in cells from lean subjects, but expressed per gram of tissue the opposite result was found. The oxygen consumption of the total AT organ was higher in obese than in lean subjects. The energy expenditure of AT constituted approximately 4% of the estimated 24-h energy expenditure in both groups. It is concluded that obese subjects do not maintain their obesity because of a reduced energy expenditure of the total AT (or of the total body). After a partial weight reduction in five subjects, the energy metabolism tended to change in direction toward the conditions seen in lean subjects. However, it is still an open question whether the observed energy metabolic aberrations of obese human AT are only secondary to the obese state or partly primary and thus of etiological importance.

Adipose Tissue↗
PubMed1989

Effects of prazosin in men with symptoms of bladder neck obstruction and a non-hyperplastic prostate.

In a double blind cross-over study, the selective alpha 1-adrenoceptor blocker prazosin was given to eleven men with a non-hyperplastic prostate and with symptoms of bladder neck obstruction. During prazosin treatment maximum and average flow rates increased and residual urine was reduced. Prazosin did not change any pressure variables recorded. All patients had antegrade ejaculation and no side effects were reported. It is concluded that in selected patients with bladder outlet obstruction, prazosin may be a therapeutic alternative to bladder neck incision.

Adult↗
PubMed1988

Immunoreactive arginine vasopressin (AVP) and effects of AVP in the human vas deferens.

Immunoreactive (IR) arginine vasopressin (AVP) was found to occur in the epididymal part of the human vas deferens. Segments from nine different subjects all contained IR-AVP in concentrations ranging from 37 to 717 fmol/gm. wet weight, concentrations severalfold higher than those normally found in the circulation. IR-AVP was shown by high performance liquid chromatography to elute in the same position as synthetic AVP. AVP added to isolated preparations of the human vas deferens induced concentration-related repetitive phasic contractions without significant changes of baseline tension. These contractions seemed to be mediated via stimulation of vasopressin V1-receptors and were abolished in the presence of vasopressin antagonists. Contractions induced by electrical field stimulation were frequency-dependent and sensitive to tetrodotoxin and prazosin. They were not affected by the vasopressin antagonists used. AVP increased the response to electrical field stimulation and this effect was inhibited by vasopressin antagonists. The results suggest either that circulating AVP is taken up and accumulated by the human vas deferens, and/or that AVP is synthesized locally. They do not suggest co-release of AVP and noradrenaline from nerve endings. The physiological role of the AVP occurring in the human vas deferens remains to be established.

Adult↗
PubMed1988

Effects of prazosin and carbachol in patients with benign prostatic obstruction.

To eight patients with benign prostatic obstruction (BPO), prazosin and placebo were given in a double blind cross-over manner. Prazosin decreased significantly residual urine volume and increased maximum and average flow rates. Neither when treated with prazosin nor with placebo, did the patients improve their ability to empty the bladder after injection of carbachol (0.25 mg) s.c. The only significant effect of carbachol on urodynamic variables was an increase in intravesical premicturition pressure. This was observed both when the patients were treated with prazosin and with placebo. Fourteen patients with BPO were given oral carbachol in maximally tolerated doses (6 or 12 mg/day) during a 2 week period. Despite producing significant systemic side effects in all patients, carbachol did not change any of the urodynamic variables tested. It is concluded that carbachol does not further improve bladder emptying in BPO patients given prazosin. Oral carbachol has no effects on bladder emptying in these patients.

Aged↗
PubMed1988

Effects of pinacidil on bladder muscle.

Infravesical outflow obstruction and bladder hypertrophy are often associated with bladder hyperactivity causing frequency, urge and urinary incontinence. This hyperactivity may be due to a supersensitivity to depolarising stimuli. Drugs that inhibit smooth muscle activity by opening K+ channels, resulting in hyperpolarisation, would therefore seem to be an attractive therapeutic principle. Pinacidil is an effective vasodilator classified as a K+ channel opener. The drug has been shown to effectively depress spontaneous contractile activity, the contractions induced by low (less than 40 mmol/L) concentrations of K+, carbachol and by electrical stimulation of nerves in isolated normal human bladder tissue and also in normal and hypertrophied rat bladder. The effect was more pronounced in hypertrophied detrusor. Pinacidil in concentrations inhibiting muscle activity also increased the efflux of 86Rb in bladder tissue. In vivo pinacidil suppressed spontaneous contractile activity in rats with infravesical bladder obstruction and detrusor hypertrophy. The findings make K+ channel openers an interesting, potentially useful therapeutic principle in hyperactivity associated with bladder hypertrophy.

Animals↗
PubMed1987

Identification and characterization of muscarinic cholinergic receptors in the human urinary bladder and parotid gland.

The binding characteristics of [3H]quinuclidinyl benzilate (QNB) to muscarinic sites in isolated plasma membrane fractions of the human urinary bladder and parotid gland were studied. QNB binding to both preparations was of high affinity and low capacity. Mean values for the apparent dissociation constants (Kd) for binding to membrane preparations from the urinary bladder and parotid glands were 22 and 34 pM and the Bmax values 234 and 456 fmol/mg protein, respectively. Significance of difference between Kd and Bmax values from the two tissues was at the level of P less than 0.005 and P less than 0.05, respectively. QNB binding was inhibited by muscarinic receptor antagonists with varying degree of effectiveness. The mean values for the inhibition constant (Ki) were significantly lower for oxybutynin, amitriptyline, and pirenzepine but higher for secoverine in preparations of the urinary bladder than of the parotid gland. The mean Ki values for quinidine and verapamil were lower in the urinary bladder than that in the parotid gland. Carbachol exhibited a marked selectivity for the urinary bladder (about 30-fold) compared with the parotid gland. The present data obtained in two human tissues that are highly cholinergic in their innervation give support to the argument for heterogeneity of the muscarinic cholinergic receptors.

Cell Membrane↗
PubMed1987

Calcium channel blockade and contractile responses in the isolated human vas deferens.

The effects of removal of extracellular calcium and of the calcium channel blockers nifedipine, verapamil and diltiazem were studied on contractions induced by electrical field stimulation and high K+-solution in isolated preparations of the human vas deferens. Electrically induced contractions were blocked by tetrodotoxin and alpha-adrenoceptor blockade. They were abolished in calcium-deficient medium, and suppressed by the calcium channel blockers in the order of potency nifedipine greater than verapamil greater than diltiazem. The maximum blocking effect of nifedipine was approximately 40%. All the blockers practically abolished K+-induced contractions. It is concluded that even if the contractile response of the human vas deferens to electrical stimulation is dependent on extracellular calcium, calcium channel blockers seem to have only a limited effect on this contraction and their capability of impairing the function of the vas deferens in patients is questioned.

Adult↗
PubMed1987

Effects of some calcium channel blockers on isolated human penile erectile tissues.

The effects of the calcium channel blockers (CCBs) verapamil, nifedipine and diltiazem on contractile activation of isolated human penile erectile tissues were investigated. Specimens of the corpus spongiosum (CS) and corpora cavernosa (CC) were obtained from men with a history of normal penile erection undergoing cystourethrectomy because of bladder malignancy. Preparations were mounted in organ baths and isometric tension was recorded. Deprivation of extracellular calcium abolished electrically induced contractions in both CS and CC preparations within 15 min.; norepinephrine (NE)-induced contractions were reduced by 90% (CS) and 83% (CC) after 30 min. All the CCBs reduced electrically induced contractions concentration-dependently, nifedipine being the most potent agent. Contractions induced by exogenous NE were depressed by about 50%, whereas high K+ (124 mM) induced responses were abolished. It is concluded that contraction in penile erectile tissues is mediated mainly by neuronally released NE stimulating postjunctional alpha-adrenoceptors. The contraction is highly dependent on extracellular calcium and can partly be inhibited by CCBs. It cannot be excluded that some CCBs injected intracavernosally may be useful for diagnosis and even treatment of erectile dysfunction. However, calcium channel blockade may not be as effective as a therapeutic principle as blockade of alpha-adrenoceptors.

Aged↗
PubMed1987

Ketanserin interaction with urethral alpha-adrenoceptors.

The selective 5-HT2 receptor blocker ketanserin was found to reduce maximal urethral pressures in healthy females by about 40% without reducing blood pressure. In vitro, ketanserin completely or almost completely reduced contractions of the isolated female rabbit urethra induced by phenylephrine, noradrenaline (NA) and electrical field stimulation. The drug was less effective against responses evoked by clonidine and 5-hydroxytryptamine (5-HT). 5-HT-induced contractions were effectively reduced by methysergide, but little affected by prazosin and rauwolscine. In concentrations exceeding 10(-7) M ketanserin significantly increased efflux of 3H in 3H-NA preloaded preparations of rabbit urethral muscle. Low concentrations of 5-HT, less than 10(-6) M, had slight inhibitory effects of 3H release, whereas 5-HT 10(-5) M caused a significant increase. It is concluded that ketanserin counteracts the effects of postjunctional alpha 1-adrenoceptor stimulation in isolated rabbit urethra. Such an effect might also explain its urethral pressure lowering action in man.

Adult↗
PubMed1987

Urovaginal fistulas: 20 years of experience with 45 cases.

We treated 45 patients with urovaginal fistulas owing to operative gynecological procedures and radiotherapy: 36 had vesicovaginal and urethrovaginal, 6 had ureterovaginal and 3 had rectovesicovaginal fistulas. Reconstruction was performed in 40 patients, mainly via a transvesical approach. There was good success in patients not given radiotherapy: 24 of 26 patients experienced primary healing and no failures were noted. Of the 14 patients treated by irradiation 9 had primary healing and 3 failed therapy. Patients with a urovaginal fistula should be referred to centers with special interest in this type of repair. An alternative surgical technique with the carbon dioxide laser deserves consideration in patients with scarred and irradiated tissue.

Adult↗
PubMed1987

Characterization of immunoreactive arginine vasopressin (AVP) in and effects of AVP on isolated human penile erectile tissues.

Arginine vasopressin (AVP), which has been shown to have a marked contractant effect on human penile erectile tissues, particularly the corpus spongiosum (CS), was demonstrated to occur in these tissues. Out of nine CS samples, eight contained vasopressin-like immunoreactivity in concentrations ranging from 3.5 to 107.2 fmol./gm. wet weight. These amounts suggest that the hormone is taken up and/or synthesized locally. The effects of four different vasopressin antagonists were characterized on human CS strips, and they were found to effectively inhibit the contractile response to exogenous AVP. However, none of these antagonists had any effects on electrically induced contractions in penile erectile tissues. These results do not favour the view that AVP is released on electrical stimulation in amounts that contract the erectile tissues. Whether or not the peptide is involved in the mechanisms controlling penile erection remains unclear.

Aged↗
PubMed1987

Early complications and long-term results of colorectal resection ad modum Rehbein for Hirschsprung's disease.

Ten years experience with Rehbein's procedure in the surgical treatment of Hirschsprung's disease (23 patients) is reported. Eleven patients were operated with a covering colostomy. Clinically overt anastomotic dehiscence was seen in 6/23 patients, being more common in the patients without a colostomy (5/12). Five of the patients with anastomotic dehiscence recovered completely after surgical intervention (4) or conservative treatment (1), whereas one patient ended up with incontinence. One patient died in enterocolitis apparently without relation to the surgical treatment. Early postoperative constipation and soiling were common, whereas at late follow-up constipation was reported only in one patient. At late follow up barium enemas showed a normal colorectal calibre in most patients. Anorectal manometry (n = 8) showed absence of normal rectoanal inhibition and rectal volumes slightly larger than among controls.

Child↗
PubMed1986

Effect of alpha, beta-methylene ATP on distal colonic and rectal motility--a possible involvement of P2-purinoceptors in pelvic nerve mediated non-adrenergic, non-cholinergic contraction.

The possible involvement of purinoceptors in the parasympathetic nervous control of large intestinal motility was investigated in cats anaesthetized with chloralose and treated with adrenolytics. Distal colonic and rectal motor responses to efferent pelvic nerve stimulation (PNS) and drugs injected close i.a., were recorded by a volumetric method. Single dose i.a. injections of alpha, beta-methylene ATP (mATP) induced colonic and rectal contractions which were resistant to atropine, hexamethonium and indomethacin, as well as to the nerve blocking agent tetrodotoxin. Repeated injections of mATP were followed by attenuated motor responses and eventually complete tachyphylaxis to the compound developed. In the presence of atropine, or a combination of hexamethonium and atropine, contractions elicited by PNS were inhibited during mATP tachyphylaxis. In contrast, prior to such anticholinergic drugs, or in the presence of hexamethonium alone, pelvic nerve mediated contractions persisted despite mATP tachyphylaxis, which did not affect the colonic and rectal contractions evoked by acetylcholine or histamine. The results suggest that P2-purinoceptors are involved in non-adrenergic, non-cholinergic large intestinal excitatory motor responses to PNS.

Adenosine Triphosphate↗
PubMed1985

Contraction and relaxation induced by some prostanoids in isolated human penile erectile tissue and cavernous artery.

Contractant and relaxant effects of prostaglandins (PG) F2 alpha, E1 and E2, prostacyclin (PGI2), the thromboxane A2 agonist U46619 and the prostaglandin endoperoxide analogue U44069 were investigated in isolated preparations of the human corpus cavernosum, corpus spongiosum and cavernous artery. In corpus cavernosum and corpus spongiosum preparations, PGF2 alpha produced concentration-dependent contractions showing rhythmic variations in tension. The contractions were effectively relaxed by carbachol and vasoactive intestinal polypeptide. U46619, U44069 and PGI2 also contracted corpus cavernosum and corpus spongiosum strips at resting tension, U46619 being the most potent drug. PGE1 and PGE2, but not PGI2 relaxed corpus cavernosum and corpus spongiosum preparations contracted by noradrenaline (NA) and PGF2 alpha. PGE1 was the more effective agent; high concentrations of PGE2 produced contraction. In cavernous artery segments, PGF2 alpha produced concentration-dependent contractions. No oscillations in tension were observed; carbachol had no relaxant action, but VIP effectively relaxed the vessels. U46619 and U44069, but not PGI2 had contractant effects on cavernous artery segments at resting tension. PGE1 and PGI2, but not PGE2 relaxed NA contracted vessel preparations; all agents (PGE2 less effectively) relaxed PGF2 alpha contracted vessel segments. It is concluded that cavernous artery and erectile tissue proper (corpus cavernosum and corpus spongiosum) differ importantly in their reaction to various prostanoids. It cannot be excluded that products of the arachidonate cascade can be involved in the control of penile tumescence and erection.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1985

Alpha-adrenoceptors and muscarinic receptors in the isolated human prostate.

Prostatic specimens of adenomatous tissue (PA) were obtained from the lateral lobe of the prostate in patients with benign prostatic hyperplasia (BPH). Non-hyperplastic specimens of the outer prostatic tissue (PC) were taken from the dorsal part of the prostate in patients undergoing cystourethrectomy. Effects of alpha-adrenoceptor and muscarinic receptor active drugs were studied. Noradrenaline (NA) and the alpha 1-adrenoceptor agonist phenylephrine induced concentration-dependent contractions in PC and PA preparations. The alpha 2-adrenoceptor agonist clonidine was without effect on PC but contracted PA preparations; it was less potent and had less intrinsic activity than phenylephrine. In PC and PA strips, the alpha 1-adrenoceptor antagonist prazosin was more effective than the alpha 2-adrenoceptor antagonist rauwolscine to inhibit NA-induced contractions. Prazosin, but not rauwolscine, inhibited electrically induced contractions in PC strips. The muscarinic receptor agonists acetylcholine and carbachol were without effect in PC and PA preparations. In both PC and PA preparations, clonidine decreased and rauwolscine increased the electrically elicited 3H-efflux after pre-loading of the tissues with 3H-noradrenaline. Carbachol and scopolamine were without consistent effects. In radioligand receptor binding experiments, the occurrence of alpha 1- and alpha 2-adrenoceptor binding sites was demonstrated; the ratio between alpha 1- and alpha 2-adrenoceptor binding sites was 3/2 in PC, but 2/3 in PA tissue. By autoradiography, muscarinic receptors were found to be localized exclusively to the glandular epithelium, consistent with the lack of contractile effects of muscarinic receptor active drugs on PC and PA preparations. Our results thus suggest that the main alpha-adrenoceptor function in human prostatic smooth muscle is of the alpha 1-type and that muscarinic receptors in the prostate are involved in processes other than control of smooth muscle contraction.

Acetylcholine↗