Effects of anoxia and glucose depletion on isolated veins of the dog.

Canine vein strips were mounted for isometric tension recording. Anoxia did not affect basal tension of saphenous and pulmonary strips mounted in standard Krebs-Ringer solution or after 30 min of incubation in glucose-free solution. Anoxia depressed the strength of spontaneous contractions of mesenteric veins; in glucose-free solution (30 min), anoxia relaxed the strips. Veins placed in glucose-free solution for more than 60 min contracted with anoxia; this contraction was not inhibited by iproveratril. When the vein strips were contracted by norepinephrine or KCl, anoxia depressed the contractions, most in mesenteric and least in saphenous preparations; this depression was greater in the absence of glucose. When oxygen was present, the absence of glucose had little effect on the response to vasoactive agents. Contractions with acetylcholine were depressed by anoxia in mesenteric and pulmonary strips but were augmented in saphenous veins; the latter potentiation was inhibited by iproveratril and by incubation in glucose-free solution. Thus, especially in the saphenous vein, anaerobic glycolysis can provide most of the energy requirements, and intracellular substrates are available for oxidative metabolism.     

Regulatory mechanisms for the spontaneous contractile force and frequency of the rat portal vein]

By the extracellular recording technique, the action potentials and spontaneous contractions of the isolated rat longitudinal portal vein strips were simultaneously recorded in the presence of varying concentrations of electrolytes, various vasoactive agents, and hormones, and the mechanisms regulating the force and frequency of spontaneous contraction of the vascular smooth muscle were investigated. A longitudinal stretch (-200% of the initial length), a higher [K+]0 (-30 mM), a lower [Na+]0, epinephrine, acetylcholine or ouabain increased both force and frequency of the phasic contractions. A lower [Na+]0 or ouabain raised basal tone of the muscle in addition to the above effects. A higher [Ca++]0 increased the contractile force, while it decreased the frequency. A lower [Ca++]0, calcium channel blocker or VIP reduced the contractile force but increased the contractile frequency. A bigger force and a higher frequency of the phasic contractions were exhibited in the portal vein strips isolated from rats with CCl4-induced experimental portal vein hypertension. They were similar to responses of the strips from the intact rats to stretch, ouabain, or higher [Ca++]0 in the presence of lower [Na+]0. These results suggest that an initiation and force of the phasic and tonic contractions depend on extracellular Ca++ concentration and influx of Ca++, and frequency of the phasic contractions, mainly on membrane potential rather than on extracellular Ca++ concentration. In the portal hypertension, permeability of the cell membrane to Ca++ is possibly increased.     

Length-tension relations of smooth muscle from normal and denervated rat urinary bladders

Urinary bladders of rats were denervated by bilateral excision of the pelvic ganglion and removed 10 days after the operation. They were filled with 0.75 ml saline and a longitudinal muscle strip was marked out, measured and dissected out. Strips from normal bladders filled with the same volume were used as controls. Denervated bladders were 4–5 times heavier than control bladders. Muscle strips from denervated bladders showed, in contrast to controls, marked phasic spontaneous contractions which were unaffected by tetrodotoxin, indicating a myogenic origin. Active tension in response to AC stimulation was measured at different lengths. In relation to the in situ length (L_{in situ}) at 0.75 ml the denervated strips had to be stretched to much greater extent than controls in order to reach optimum length (L₀) for force development. Furthermore, the denervated strips shortened less in relation to L_{in situ} than the controls. If active length-tension relations were expressed in relation to Lo, the difference between denervated and control strips was abolished. Maximal active force was the same for denervated and control strips. Water content increased significantly in denervated bladders. The results suggest a remodelling of the smooth muscle structure in denervated bladders; the characteristics of the contractile machinery seem, however, to be unaltered.     

Difference between endothelium-dependent relaxation in arterial and in venous coronary bypass grafts

Both the internal mammary artery and the saphenous vein are used to construct coronary-artery bypass grafts. We hypothesized that the release or production of endothelium-derived relaxing factor, which regulates blood flow and inhibits platelet function, may differ in venous and arterial grafts. We therefore studied endothelium-dependent relaxation in internal mammary arteries, internal mammary veins, and saphenous veins obtained from 58 patients undergoing coronary bypass surgery. Vascular rings with and without endothelium were suspended in organ chambers, and isometric tension was recorded. Acetylcholine (10(-8) to 10(-4) M), thrombin (1 U per milliliter), and adenosine diphosphate (10(-7) to 10(-4) M) evoked potent endothelium-dependent relaxation in the mammary artery but weak response in the saphenous vein (P less than 0.005; n = 6 to 27). In the mammary artery, relaxation was greatest in response to acetylcholine (86 +/- 4 percent reduction in norepinephrine-induced tension), followed by thrombin (44 +/- 7 percent) and adenosine diphosphate (39 +/- 8 percent). In the saphenous and mammary veins, relaxation was less than 25 percent. Relaxation was unaffected by indomethacin but was inhibited by methylene blue and hemoglobin (P less than 0.005 and 0.01, respectively), which suggests that endothelium-derived relaxing factor was the mediator. Endothelium-independent relaxation in response to sodium nitroprusside was similar in arteries and veins. We conclude that endothelium-dependent relaxation is greater in the mammary artery than in the saphenous vein. The possibility that this contributes to the higher patency rate among arterial grafts than among venous grafts will require further study.     

Oscillatory contractions in vertebral arteries from hypertensive subjects.

In response to several agonists, tail arteries from spontaneously hypertensive stroke prone rats (SHRSP) contract in an oscillatory manner not observed in tail arteries from normotensive rats. This study evaluated whether oscillations in force development characterize the contractile pattern of vertebral arteries from hypertensive humans. Vertebral arteries were isolated and studied within 18-24 h post mortem. Helical strips of the arteries were mounted in a muscle bath for isometric force recording. Contractile responses to serotonin (10(-7)M) and endothelin (10(-8)M) in arteries from hypertensive subjects were characterized by fluctuations in force development whereas those in arteries from normotensive subjects usually remained constant with time. The frequency of the response was approximately 1-2 contraction/relaxation cycles per min. This pattern of oscillatory contractile activity was observed in all but one of the hypertensive arteries (n = 15), and in approximately 40% of the normotensive arteries (n = 12). Oscillatory activity was converted to maintained contraction by nifedipine (10(-7)M) which also caused relaxation of the contractile response. Relaxation to acetylcholine (10(-6)M) and nitroglycerin (10(-6)M) did not alter the oscillatory contractions. Endothelium removal did not influence the oscillatory pattern of contraction. These observations suggest that oscillatory contractile activity in vertebral arteries from hypertensive subjects is related to abnormal calcium entry into the smooth muscle cells. This altered membrane property may contribute to changes in vascular reactivity in hypertension.     

Characteristics of contractile response of isolated portal veins from chronic portal hypertensive rats under altered levels of external K+, Ca2+, and norepinephrine concentrations: a comparison with normal Wistar rats

We studied contractile properties of portal veins isolated from chronic portal hypertensive rats (PHR) resulting from liver cirrhosis, a model obtained by repeated subcutaneous injections of CCl4 (2 mg/kg) twice weekly for over 45 weeks. Portal venous pressure in vivo was significantly higher in PHR (167.0 +/- 38.7 mmH2O) than in the control normal Wistar rats (NWR) (102.0 +/- 25.5 mmH2O). A pair of portal veins from PHR and NWR were mounted longitudinally in an organ bath and perfused with Tyrode's solution with different K+, Ca2+, and norepinephrine concentrations. The isometric tension was measured by a strain-gauge. Under control conditions, spontaneous phasic contractile force, corrected by cross-sectional area, was greater, and the frequency was lower in PHR than in NWR preparations. The averaged peak contractile force measured at different [K]o (5.4-86.4 mM) was also greater in PHR than in NWR. Force of the tonic contraction measured at different [Ca]o (0.45-5.4 mM), under conditions of 86.4 mM [K]o was significantly larger in PHR than in NWR preparations. However, the Ca2+ sensitivity of both preparations was the same. D-600 (greater than or equal to 0.1 microM) inhibited the tonic contraction in both preparations with an identical sensitivity to the drug. In the presence of norepinephrine (10 microM), the Ca2+ sensitivity of the tonic contraction increased both in PHR and NWR preparations. The increase was more pronounced in PHR and was completely reversed in the presence of the alpha 1-adrenoceptor blocker, prazosin (0.1 microM). The alpha 1-adrenoceptor sensitivity to norepinephrine was not altered in PHR preparations. The rate of Ca2+ release and uptake of intracellular Ca2+ seemed identical in both preparations. Thus, in the absence of norepinephrine, the phasic and tonic contractile forces of portal veins from PHR are larger than that of NWR, probably due to increased membrane Ca2+ permeability. The PHR preparations have a higher affinity for external Ca2+ in the presence of norepinephrine, an additional factor contributing to elevation of portal blood pressure in the presence of chronic liver cirrhosis.     

Differential actions of exogenous and intracellular spermine on contractile activity in smooth muscle of rat portal vein

Effects of the naturally occurring polyamine spermine on electrical and contractile properties of the rat portal vein were studied. 1 mM spermine nearly abolished spike activity and spontaneous contractions and decreased the intracellular Ca²⁺ concentration ([Ca²⁺],). The phasic force responses to 0.1 and 1 μM phenylephrine were partially inhibited, but not the sustain plateau contraction caused by 5 /IM phenylephrine. The Ca²⁺-force relation in high-K⁺ (128 mM)-depolarized veins was shifted to the right, EC₅₀ for Ca²⁺ increasing from 0.50 ± 0.03 mM (control, n= 8) to 0.65 ± 0.06 and to 0.94 ± 0.03 at 1 (n – 4) and 10 (n = 3) mM spermine, respectively. However, at a Ca²⁺ concentration of 2.5 mM, giving maximal force, there was no effect of spermine (1 mM) on either force or [Ca²⁺],. Whereas extracellular spermine thus reduced contractile activity at moderate levels of stimulation, increased intracellular concentration of spermine potentiated the force response to Ca²⁺. Intracellular loading of spermine by reversible permeabilization increased its concentration by 2–3 times. The spontaneous activity and response to phenylephrine were unchanged. However, the Ca²⁺-force relation of depolarized veins was shifted to the left, EC₅₀ decreasing from 0.51 ± 0.04 mM in controls (n= 7) to 0.36 ± 0.02 mM in the loaded veins (n= 9). Spermine increased Ca²⁺-activated force in portal veins permeabilized with β-escin. The degree of potentiation was consistent with observed effects in spermine-loaded intact veins. The results suggest that spermine at physiological intracellular concentration may contribute to the determination of Ca²⁺ sensitivity in vascular smooth muscle cells.     

Noradrenaline-induced smooth muscle relaxation in the specific region of canine facial vein: implications for facial and cranial circulation

This study was performed to investigate the heterogeneity of physiological and pharmacological properties in segments of the facial veins with special reference to selective brain cooling. Canine facial veins were isolated and the isometric tension of each segment was measured using the organ bath technique. Vessels in the segments of the facial veins that run opposite to the buccal cavity automatically produced myogenic tone and tended to show spontaneous contractions, but vessels in other segments did not. When no contractile agent was used for precontraction, noradrenaline and adrenaline produced dose-dependent relaxations in the former venous segments, but contractions in the latter ones. A Schild plot analysis for metoprolol against denopamine and for ICI118,551 against salbutamol showed that the venous segments running opposite the buccal cavity contained both beta(1)- and beta(2)-adrenoceptors, but the other venous segments contained only beta(2)-adrenoceptors. Electrical field stimulation-induced tetrodotoxin-sensitive relaxations in the former venous segments were diminished by pretreatment with metoprolol, but not with ICI118,551, indicating that the electrical stimulation-induced relaxation may be related to the activation of beta(1)-adrenoceptors in the venous smooth muscles. In conclusion, the heterogeneity of the functional properties, especially in the distribution of beta-adrenoceptors, in different segments of canine facial veins was observed in the present study, and autoregulatory mechanisms, humoral mechanisms, and neural mechanisms were suggested to affect cranial venous drainage.     

Diabetes mellitus and responses of the urinary bladder to acetylcholine: an in vitro study

This study was prompted by the inconsistent reports and apparent controversies that exist in the biomedical literature on the responses of diabetic bladder strips to cholinergic nerve stimulation or exogenously-administered muscarinic agonists, especially acetylcholine (ACh). In the present study, acetylcholine-induced contractions of urinary bladders isolated from normoglycaemic (normal) and streptozotocin-treated, diabetic Wistar rats were examined under physiological conditions. Mechanical contractile changes of the isolated urinary bladders of STZ-treated, diabetic rats in response to bath-applied acetylcholine were compared with those obtained from isolated urinary bladders of normal, age-matched, control rats. Results obtained show that urinary bladders from diabetic rats were always more spontaneously active after mounting, than those of the age-matched normal, control rats. ACh (10(-8)-10 (-4) M) provoked concentration-related, atropine-sensitive contractions of the isolated urinary bladders of both diabetic and age-matched normal, control rats. However, acetylcholine always induced more powerful and greater contractions of the diabetic bladders compared with bladders from the age-matched normal, control rats. The magnitude and/or intensity of the diabetic bladder enhanced contractile responses to ACh continued to increase as the diabetic state of the animals progressed.     

Membrane current and contraction in frog atrial fibres

1. Membrane current and mechanical activity were recorded from short segments of frog atrial muscle strips using a double sucrose gap voltage clamp arrangement. Experiments were performed at 4-7 degrees C. Two types of contraction were observed dependent upon the duration of the clamp.2. Short-lasting depolarizations caused a flow of Ca inward current, I(Ca), and development of a phasic contraction. Time to peak tension approximated 400 msec. Both I(Ca) and contraction, as functions of membrane potential, had a threshold of about - 40 mV and were maximal at inside positive potentials in normal Ringer fluid. Peak tension decreased at strong depolarizations.3. The minimum time of depolarization required for initiation of a phasic contraction was 40-70 msec. The time necessary for full activation of contraction was 200-300 msec and comparable to the period of time covered by the flow of I(Ca).4. There was no marked change in peak tension upon repetitive depolarization to the same membrane potential.5. Restoration of (phasic) contractility after a preceding contraction was strongly dependent on the level of membrane potential between conditioning and test pulse. Restoration was half complete at potentials around - 45 mV.6. Long-lasting depolarizations generated tonic (sustained) contractions superimposed on the phasic (transient) ones. Threshold potential for initiation of tonic contractions was usually positive to the threshold of phasic contractions. The time taken to attain the final level of tension ranged between 0.7 and 3 sec. Plateau tension, as a function of membrane potential, increased with increasing depolarization and reached a flat maximum at about + 50 mV in normal Ringer fluid.7. At membrane potentials near zero level, plateau tension developed by the tonic mechanism was about twice peak tension due to phasic contraction.8. Removal of Ca ions from the external medium resulted in an almost complete abolition of phasic contraction within 1-2 min and a gradual decrease of tonic contraction during the first 10 min. Application of a ;Ca inhibitor' to normal Ringer fluid caused a strong reduction of both I(Ca) and phasic contraction without affecting tonic contractions.9. It is concluded that phasic contractions are directly activated by the flow of I(Ca). Generation of tonic contractions may be attributed to a Ca transfer mechanism different from I(Ca) or a release of Ca from intracellular stores.     

Myosin light chain phosphorylation during phasic contractions of tracheal smooth muscle

Rapid, coordinated contractions of tracheal smooth muscle were elicited by either direct electrical depolarization of muscle cells or treatment with tetraethylammonium which produced spontaneous phasic contractile activity. Both types of contraction were blocked by the calcium channel antagonist verapamil, indicating that these contractions are supported primarily by calcium of extracellular origin. With direct electrical stimulation, force was biphasic and phosphate content of the phosphorylatable light chain (P-light chain) of myosin increased rapidly (2.5 s) from 0.1 to 0.4 mol phosphate/mol P-light chain, then decreased to levels above resting values. Phosphorylation increased more rapidly than force. Under conditions of spontaneous activity, phasic contractions occurred above a level of basal tone significantly greater than resting force, and minimum values of phosphorylation measured at the base of contraction were significantly greater than those observed in the resting muscle. Phosphorylation oscillated with force (from 0.2 to 0.4 mol phosphate/mol P-light chain) and peak values occurred during the rising phase of contraction. Time courses of phosphorylation and force showed evidence of a prolonged state of activation of myosin following dephosphorylation. These results suggest that phosphorylation and dephosphorylation of myosin P-light chain are sufficiently rapid to participate in regulation of contractility during phasic mechanical activity.     

Alteration of the responses of gastric smooth muscle to endothelin in streptozotocin-induced diabetic rats.

Diabetic gastropathy is suggested to be the result of not only an autonomic neuropathy but also to disorder of the spontaneous rhythmic motility of the gastric smooth muscle. Attempts were made to investigate the alteration of the effects of endothelin-1 (ET-1), which is known to enhance the spontaneous activity of gastrointestinal smooth muscle, on gastric activity in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic rats were prepared by the injection of Sprague-Dawley (SD) rats with STZ (i.p.). Isometric mechanical responses were recorded in isolated circular smooth muscle strips of the stomach antrum, to measure changes in the rhythmicity of the smooth muscle. ET-1 (10 nM) significantly elevated the resting tension and the frequency of spontaneous contraction, but did not alter the amplitude of the spontaneous oscillatory contractions in normal rats. In diabetic rats, ET-1 elevated the resting tension, and spontaneous contractions were increased in frequency, however they were decreased in amplitude. In normal rats, sarafotoxin S6c (S6c, 10 nM), a selective ET(B) receptor agonist, elevated the resting tension slightly and increased both the frequency and amplitude of the spontaneous contractions. However, S6c significantly elevated the resting tension alone in STZ-induced diabetic rats. Selective stimulation of endothelin type A (ET(A)) receptors with ET-1, in the presence of a selective antagonist of ET(B) receptors, produced similar responses in the gastric muscle of both normal and diabetic rats. These results indicate that ET-1 elevates the resting tension and increases the frequency of the spontaneous oscillatory contractions in both normal and STZ-induced diabetic rats, to a similar extent. However, the specific actions on ET(B) receptors were quite different between the two: the elevating actions on the resting tension were much greater in STZ-diabetic rats than in normal rats. The results suggested the facilitation of ET(B) receptor signaling in the antrum during the pathogenesis of diabetic gastropathy.     

Mechanical properties of isolated human oesophageal submucosal veins.

The mechanical properties of isolated human oesophageal submucosal veins were investigated. The veins were without tone or spontaneous activity and possessed a high compliance, tolerating a stretch of several hundred per cent of the length at which the vessels were first able to contract with only minor increases in passive tension. The veins were capable of producing active tension when the length exceeded 30% of L0 (the length at which maximum wall tension (T0) was developed when activated by 124 mM K(+)-solution). The veins from the oesophageal body (OB) had a higher L0 than the veins from the gastrooesophageal junction (GOJ) (1180 microns vs 820 microns) and T0 was correspondingly higher (1.1 mN/mm vs. 0.6 mN/mm). However, there was no significant difference in the calculated effective transmural pressure (P) at the two locations. Noradrenaline induced contractions in all preparations tested with a maximum response equivalent to the tension achieved after stimulation with 124 mM K(+)-solution, pD2 values for noradrenaline in vessels from the oesophageal body and the gastroesophageal junction were 7.03 +/- 0.28 (mean +/- SEM) and 7.15 +/- 0.20, respectively. The present model seems suitable for future studies of human oesophageal submucosal veins from the oesophageal body and the gastrooesophageal junction.     

The actions of altered osmolarity on guinea-pig detrusor smooth muscle contractility and intracellular calcium

The study measured the effects in vitro of changing extracellular osmolarity on the contractility of detrusor smooth muscle strips. The data were interpreted in the context of separate measurements from isolated cells of alterations to the intracellular [Ca2+], [Ca2+]i. Increased osmolarity (300-700 mosmol l-1) reduced phasic contractions but increased resting tension regardless of whether sucrose, LiCl or NaCl were used as osmolytes. [Ca2+]i was decreased slightly only when NaCl increased osmolarity, otherwise it was unchanged. The contractile effects may be explained by tissue shrinkage and reduction of detrusor excitability. Lowered osmolarity (300-64 mosmol l-1) decreased phasic contractions but increased resting tension and [Ca2+]i. The raised resting tension was due solely to low osmolarity and was independent of changes to [Na], [Cl] or ionic strength. The rise of [Ca2+]i was due partly to Ca2+ influx through Na(+)-Ca2+ exchange but a fraction was independent of extracellular Ca, unaffected by Gd3+, and persisted in the presence of caffeine. By contrast, reduction of phasic tension was due mainly to the reduced ionic strength, not osmolarity. The results do not support the presence of functional stretch-activated channels and suggest only a minor role for Na(+)-Ca2+ exchange under these conditions. However, they do suggest an intracellular source of Ca2+, which is independent of the sarcoplasmic reticulum.     

Vasa vasorum quantification in human varicose great and small saphenous veins

Recent research regarding saphenous vasa vasorum (VV) has focused on two main topics: the VV during varicogenesis in chronic venous insufficiency and the VV in saphenous grafts used in reconstructive vascular surgery. Our aim has been (i) to establish a technique for the histological quantification of the VV in human varicose great and small saphenous veins and (ii) to describe the density and distribution of the vasa vasorum within varicose veins. Great (n=11) and small (n=5) saphenous veins (length, 15-40cm) were collected from 12 patients who were undergoing venous stripping due to chronic venous insufficiency (Clinical-Etiology-Anatomy-Pathophysiology class 2-3). The veins were divided into 5-cm long segments. In total, 92 tissue blocks were collected to trace the variability of the density and distribution of the vasa vasorum in the proximo-distal direction. The endothelium was detected by immunohistochemistry using the von Willebrand factor. We quantified the number of microvessel profiles per section area and the relative distance of the microvessels from the outer border of the adventitia. The VV did not exhibit a preferential orientation in the varicose veins. VV density profiles were highest in the middle third of the venous wall and lowest in the inner third of the venous wall. Both the density and distribution of VV were uniform along the veins, and no differences were observed between the great and small saphenous veins. The VV density was statistically independent of the relative distance from the adventitia. The usability of this technique for perioperative frozen sections remains to be tested.     

Effect of neurotensin on contractile activity and [3H]acetylcholine release in cat terminal ileum during different postnatal periods.

The effect of neurotensin (NT) on the contractile activity of circular and longitudinal strips from the terminal ileum of 15-, 30-, 60-day-old and adult cats as well as on the resting and electrically-evoked release of [3H]acetylcholine (ACh) was studied. Radioactivity was measured by liquid scintillation spectrometry and the effect of NT was evaluated by the S2/S1 ratio. In the circular muscle strips NT (1-100 nM) inhibited spontaneous contractions in all age groups. In the longitudinal strips the effect of NT was concentration- and age-dependent. NT at a concentration of 1 nM had no effect on the spontaneous activity in 15-day-old cats, but in the other age groups in 70-80% of the cats it inhibited spontaneous contractions. The response to 10 and 100 nM NT was either biphasic (relaxation followed by contraction) or inhibitory: in 15-day-old cats the response was biphasic only and with increasing age the percentage of strips responding with inhibition of the contractions increased. Neither substances affecting adrenergic and cholinergic transmission nor TTX changed the inhibitory response to NT. The contractile component of the biphasic response was TTX-resistant in all age groups and was significantly decreased by scopolamine in 60-day-old and adult cats. NT increased both resting and electrically-evoked release of [3H]ACh which was not changed by TTX. In the presence of the peptide the S2/S1 ratio increased as NT-induced [3H]ACh release in the strips of adult cats was higher than that in young cats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pentobarbital and contraction of vascular smooth muscle.

This study, with isolated rat aortic strips and portal veins, was undertaken to : 1) study the effects, if any, of pentobarbital Na (PTB) (5 x 10(-5) to 2 X 10(-3) M) on reactivity to epinephrine, serotonin, and KCl; 2) determine whether certain concentrations of PTB induce direct actions on aortic strips and portal veins; and 3) gain some insight into how these effects are brought about. The results indicate that PTB can: a) inhibit development of spontaneous mechanical activity in these vessels in anesthetic concentrations; b) dose-dependently attenuate contractions induced by epinephrine, serotonin, and KC1; c) cause a noncompetitive type displacement of the dose response curves of these vasoactive agents; d) attenuate Ca2+- induced contractions of potassium-depolarized aortic strips and portal veins concomitant with a dose-dependent displacement of these dose-response curves to the right; and e) rapidly relax drug as well as Ca2+ -induced contractions of aortas and portal veins. In addition, the data indicate that rat portal venous smooth muscle is more sensitive to the inhibitory actions of PTB than rat aortic smooth muscle. Overall, these data suggest that concentrations of PTB used to induce surgical anesthesia can exert profound depressant effects on at least two different types of vascular smooth muscle that may be related to actions on movement and/or translocation of Ca2+.     

A comparison of the relaxation responses of isolated cavernosal smooth muscles by endothelium-independent and endothelium-dependent vasodilators in diabetic men with impotence.

This study was intended to explore the effects of endothelium-independent, direct smooth muscle relaxants(papaverine, verapamil) and endothelium-dependent vasodilators(acetylcholine, bradykinin, adenosine) on the isolated cavernosal smooth muscle strips taken from diabetic men with impotence. When smooth muscle contraction was evoked with norepinephrine for the study of relaxation to these vasodilators, the tension induced was similar in diabetic and non-diabetic men with importance. Papaverine showed the strongest relaxation response followed by verapamil, acetylcholine, bradykinin and adenosine both in non-diabetic and in diabetic men. Relaxation of the cavernosal tissues to endothelium-independent vasodilators was similar in non-diabetic and diabetic men. However, the relaxation response of the tissues to endothelium-dependent vasodilators was significantly reduced in the diabetic group compared with that in the non-diabetic group (p < 0.05). In conclusion, the impairment of endothelium-mediated relaxation of cavernosal smooth muscle seems to play a more important role in the pathogenesis of diabetogenic impotence rather than the problem of smooth muscle itself. This finding forms a rational basis for the use of intracavernosal injections of vasodilators to induce endothelium-independent relaxation of the cavernosal smooth muscle in the patients with diabetogenic impotence.     

Postpartum changes in the mechanical responses of the circular muscle of rat uterus

The circular muscle strips were isolated from rat uterus 10-60 h after parturition, and the electrical and mechanical responses were investigated. The muscle strips exhibited a variety of contractile activity ranging from frequent spontaneous contractions generated on an elevated muscle tone to a sustained contracture, when incubated with Mg-free Krebs solution. The muscle tone was lowered, and phasic contractions were abolished when the external Ca was removed. Muscle tone was also lowered by addition of 1.2 mM Mg, 1 mM spermidine, or 1 mM tetracaine. The membrane potential was about -25 mV in a muscle which exhibited a contracture, and the membrane was hyperpolarized by 20-25 mV by the (1.5-4.5 x 10(-5) M) caused a gradual decrease in muscle tone, and the that Ca-influx was increased, for which prostaglandin(s) was membrane was hyperpolarized. In view of the above results, it is hypothesized that Ca-influx was increased, for which prostaglandin(s) was probably responsible, in the circular muscle of postpartum rat uterus, thereby elevating the muscle tone in Mg-free solution.     

Effect of microvibration on activity of ureteral and portal smooth muscles.

Spontaneous contractions were elicited by microvibrations (1--80 Hz, 50--400 micron) imposed upon quiescent ureter and portal venous smooth muscles of dogs. The microvibrations increased the rate of spontaneous contractions. A microvibration of larger amplitude gave rise to a more profound increase at each frequency. The acceleration was often accompanied by a reduction in contractile force. The positive chronotropic effect was enhanced by increases in frequency from 20 to 40 Hz and not affected by administration of autonomic blocking agents and tetrodotoxin, but disappeared in a Ca-free environment and reappeared on addition of Ba2+. the simulating action of microvibration was almost proportional to external Ca2+ concentrations ranging from 2.2 to 6.2 mM. The microvibrations were able to elicit spontaneous activity in the preparation, which had been made quiescent by administration of Mn2+. These findings suggested that the positive chronotropic effect may be closely related to an increased Ca2+ influx through the membrane of smooth muscle. Active tension in the ureter in a state of contracture was depressed by imposed microvibrations.