Influence of X-irradiation on the motor activity of rat urinary bladder in vitro and in vivo.

Preparations of rat detrusor vesicae urinariae exposed to 50 kV X-irradiation with 10 to 200 Gy (single dose) at dose-rates of 30 and 60 Gy/min reacted immediately with a dose and dose-rate dependent reversible or persistent increase (up to ten hours) of the basal tone and an increase or a decrease of the acetylcholine contractile response. The motor activity was recorded isotonically. For measurements of time changes following treatment in vivo the bladder was locally irradiated from lateral position with single 300 kV X-ray doses of 10, 25 and 50 Gy. The motor reaction of isolated detrusor preparations to acetylcholine had a threshold concentration in control animals of 2.3 X 10(-10) mol/l (n = 33); the sensitivity to acetylcholine was diminished as early as one to two hours after local irradiation with 50 Gy as reflected in a ten times higher threshold concentration, which decreased further with time past treatment up to 40 days. The inhibitory effect after 25 Gy was weaker. The contractile response of acetylcholine at different concentrations (10(-10) to 10(-5) mol/l) was also diminished after irradiation (50 Gy). It is suggested that the pathophysiological reactions of the radiogenic bladder are based on multifactorial mechanisms and X-ray induced tonic contraction as well as inhibition of the acetylcholine contractile response could be essential factors for the clinically observed hypertonia of the irradiated bladder ("radiogene Harnblase") and its functional volume decrease as well as of the diminished pressure during micturition.

Reactions of isolated rat aorta to X-irradiation.

The reaction of isolated helical strips of rat aorta to X-irradiation was studied: X-rays (50 kV) induced a reproducible, reversible contractile response at threshold doses of 2.5 Gy (60 Gy/min) and 10 Gy (30 Gy/min). After repeated irradiation with the same doses at equal time intervals and constant dose-rate (for example 50 Gy every 15 min, dose-rate 60 Gy/min) the contractile response was progressively diminished, i.e. a tachyphylaxis appeared. The preparations still reacted even after total doses over 1000 Gy. The X-ray induced contractile responses were dose- and dose-rate dependent. Quantitative analysis indicated no essential differences in the radiation-induced contractile response when recorded under isometric or isotonic conditions. After hypothermia (20 degrees C) or hyperthermia (42 degrees C) no visible radiation response could be induced. Part of the aortic strips were spontaneously active: X-ray doses of 5 to 10 Gy stimulated, while doses of 100 to 200 Gy inhibited or blocked the spontaneous phasic activity. A comparison between the immediate X-ray reaction of vascular and non-vascular smooth muscle preparations is given. Participation of cholinergic and adrenergic mechanisms in the X-ray induced contractions of rat aorta seems to be ruled out, because the blocking agents atropine, phentolamine, and bretylium had no effect.

Contractile reaction of isolated frog aorta after X-irradiation.

The action of X-rays (50 kV, filtered by 0.3 mm Al) on helical strip of frog aorta (rana esculenta) has been investigated. The isolated preparations have a stable basal tone and are radio-sensitive to X-rays which induce reversible, dose-dependent, contractile responses. After repeated irradiation tachyphylaxis appears. The threshold doses are about 250 Rat 3 to 6 kR/min, antiadrenergic (phentolamine, propranolol), anticholinergic (atropin), antihistaminic (Neo-Bridal) and serotoninergic (Deseril) drugs have no visible influence on the X-ray induced reaction, i.e. these action mechanisms of the irradiation-induced contraction do not seem probable. Theophylline and cAMP inhibit the X-ray contraction probably non-specifically. Indometacin also inhibits the X-ray contraction: this suggests participation of prostaglandin-mechanism on the contraction of frog aorta after irradiation.

Differences in the physiological response and ultrastructure of human and guinea pig vas deferens. Effects of prostaglandins, irradiation, and temperature.

Marked differences were observed in the mechanical reactions of human and guinea pig vas deferens to prostaglandins, irradiation, and cooling. In human preparations prostaglandin E1 (0.1-1 ng/ml) had an augmentory effect on the contractile response after electrical neurostimulation (10 Hz, 0.3 ms, 3 s), but no visible influence (at concentrations ranging from 1 ng to 10 micrograms/ml) on the contractile response after electrical muscle stimulation (10 Hz, 40 ms, 3 s). In contrast, in guinea pig preparations (PGE1 (0.1-1 ng/ml) had an inhibitory effect on the contractile response after electrical neurostimulation and an augmentory effect (0.1-1 micrograms/ml) on the contractile response after electrical muscular stimulation. Human vas deferens showed higher radiosensitivity than guinea pig preparations. The neurotransmitters acetylcholine and catecholamines increased the radiosensitivity of guinea pig preparations, but not of human ones. Vas deferens reacted to short-time (15-120 s) cooling with an immediate temporary contraction, at 25 degrees C of short (seconds), at 5 degrees C of long (minutes) duration; after rewarming (5-37 degrees C) a second contraction appeared in guinea pig preparations, but not in human ones. Whereas the contraction to electrical neurostimulation (10 Hz, 0.3 ms, 3 s) was abolished in human preparations by cooling, it was only inhibited in guinea pig vas deferens. Electron microscopy showed differences in the ultrastructure of human and guinea pig vas deferens. Muscle cells were more widely separated in human vas deferens (generally 400 nm or more) than in guinea pig (approximately 100-200 nm), and the intracellular space in human preparations contained more collagen. The axons in human preparations contained predominantly large granular and agranular vesicles, those in guinea pig preparations small granular and agranular vesicles. The possible correlation between the physiological response of human and guinea pig vas deferens and the ultrastructural differences is discussed. The results indicate the possibility that other pharmacophysiological and toxicological phenomena could be essentially different in human and guinea pig material.

Effects of Urol on isolated neuromuscular preparations of guinea pig and rat urogenital tracts (ureter, detrusor vesicae and vas deferens).

Urol--a compound of extracts from rad. Rubiae, sem. Ammeos visnagae, herb. Virgaureae, rad. Taraxaci and aescin - induced changes in the mechanical activity (isotonic registration) of guinea pig and rat ureter, detrusor and vas deferens preparations when applied at concentrations of 10 ng to 100 microgram/ml. Low concentrations (10 ng to 1 microgram/ml) had an inhibitory effect on the spontaneous mechanical phasic activity in about half of the ureter preparations and a stimulatory effect on the remaining preparations; higher concentrations (1-100 microgram/ml) had a predominantly inhibitory effect. Urol acted similarly on detrusor preparations; it inhibited (up to 30% at 10 mg/ml) or stimulated the contractile responses after nerve stimulation (10 Hz, 0.3 ms, 3 s); it had a purely inhibitory effect on the contractions of vas deferens after nerve stimulation and had an inhibitory effect on X-ray-induced contractions in detrusor muscle preparations. The effects of Urol were observed at therapeutically relevant concentrations (about 1-10 microgram/ml). The nonuniform effects of Urol on urinary tract preparations suggest a reason for the differences in therapeutic response observed in clinical trials.

Effects of buphenin on the rat portal vein.

The vasodilator and tocolytic substance buphenin (10 mumol/l) stimulated the spontaneous phasic activity of some (8 out of 18) isolated rat portal vein preparations; 0,1-1 mmol/l buphenin diminished or abolished the activity in all preparations. The isotonic and isometric tonic contractions of portal vein in response to adrenaline, noradrenaline and phenylephrine (0,1-1 mumol/l) disappeared almost completely after addition of buphenin in equimolar concentrations, whereas acetylcholine contractions persisted. The beta-adrenergic blocking agents propranolol and dichloisoprenaline (10 mumol/l) only slightly antagonized the inhibitory effect of buphenin on the contractile responses to catecholamines. It is concluded that buphenin exerts dual action upon rat portal vein: the drug partially stimulates the beta-receptors and partially blocks the alpha-adrenergic receptors.

Immediate mechanical reactions of isolated human detrusor muscle on x-irradiation.

The mechanical activity (isotonic registration) of isolated detrusor (smooth) muscle preparations from the human urinary bladder (surgical material) is investigated. The preparations reacted on X-irradiation (50 kV) with an immediate dose-dependent tonic contraction at threshold-doses of 100 to 1000 R (1 to 3 kR/min). The contraction was either reversible, semireversible or persistent, and the basal muscle tone was elevated. A tachyphylactic reaction was observed. The phasic activity of the preparations was temporarily increased, then inhibited after irradiation. The radiation-induced changes of the human and guinea-pig detrusor muscle are compared and their possible relation to the functional disturbances of the urinary bladder after radiotherapy is discussed.

[Influence of 2-mercaptoethylguanidine on blood pressure reaction to bradykinine and kallidine in normal and spinal rats]. / Beeinflussung der Blutdruckreaktion auf Bradykinin und Kallidin durch 2-Mercaptoäthylguanidin (MEG, AET) bei normalen und Spinalratten

2-Mercaptoethylguanidine (MEG) enhances the hypotension reaction to bradykinine and kallidine injections. In normal and spinal rats the secondary rise of the blood pressure after bradykinine, caused by catecholamine liberation, was transformed into a hypotension through MEG. These effects are partially interpreted as sympatholytic effects of MEG.

[The late bladder reaction following radiotherapy of a cervix carcinoma]. / Zur späten Harnblasenreaktion nach Bestrahlung des Kollumkarzinoms

This study presents the cystotonometric checks of trends in 102 patients with irradiated carcinoma of the cervix up to the time of the so-called five year survival recovery. As compared with a standard control group concerning the function of the urinary bladder a distinct tendency to hypertonia is realized and attributed as inevitable to radiotherapy. The moderate load being present before the onset of irradiation is mentioned, resulting from diagnostic operations and from the primary disease. Based on these observations, functional findings which allow objectivation appear to be indicated, the aim being to recognize, as early as possible, the increase of vesical reactions with regard to gynecologic radiotherapy and later follow-up care.

Action of tetrodotoxin on the contractile responses of isolated guinea-pig urinary bladder preparation to x-irradiation and to electrical stimulation.

Tetrodotoxin (10- minus 8 to 10- minus 6 g/ml) blocked the contractile responses of isolated guinea-pig urinary bladder preparation to electrical (25 and 100 Hz) neural but not to transmural stimulation and to X-irradiation (50 kV, 20 kR/min, 20 kR). The irradiation had no influence on the bladder responses to electrical and hormonal (acetylcholine and histamine) stimulation. It is concluded that the X-ray-induced contraction is of myogenic origin and that it is possibly not related to the electro-mechanical coupling system.