Safety and feasibility of minimally invasive esophagectomy for elderly esophageal cancer patients.

The number of elderly patients with esophageal cancer has increased in recent years. The use of thoracoscopic esophagectomy has also increased, and its minimal invasiveness is believed to contribute to postoperative outcomes. However, the short- and long-term outcomes in elderly patients remain unclear. This study aimed to elucidate the safety and feasibility of minimally invasive esophagectomy in elderly patients. This retrospective study included 207 patients who underwent radical thoracoscopic esophagectomy for thoracic esophageal squamous cell carcinoma at Kobe University Hospital between 2005 and 2014. Patients were divided into non-elderly (<75 years) and elderly (≥75 years) groups. A propensity score matching analysis was performed for sex and clinical T and N stage, with a total of 29 matched pairs. General preoperative data, surgical procedures, intraoperative data, postoperative complications, in-hospital death, cancer-specific survival, and overall survival were compared between groups. The elderly group was characterized by lower preoperative serum albumin levels and higher American Society of Anesthesiologists grade. Intraoperative data and postoperative complications did not differ between the groups. The in-hospital death rate was 4% in the elderly group, which did not significantly differ from the non-elderly group. Cancer-specific survival was similar between the two groups. Although overall survival tended to be poor in the elderly group, it was not significantly worse than that of the non-elderly group. In conclusion, the short- and long-term outcomes of minimally invasive esophagectomy in elderly versus non-elderly patients were acceptable. Minimally invasive esophagectomy is a safe and feasible modality for elderly patients with appropriate indications.

Inhibitory effect of calmodulin inhibitors on palytoxin-induced K+ release from rabbit erythrocytes.

Palytoxin (PTX) caused K+ release from rabbit erythrocytes at a concentration as low as 10(-11) M. The K+ release due to PTX at a concentration below 10(-9) M was dependent on Ca2+ in medium. The effect of Ca2+ was substituted fully by Sr2+ and partially by Ba2+. W-7 (2 X 10(-4) M), a known inhibitor of calmodulin, markedly inhibited the rate of K+ release due to PTX. W-5 (2 X 10(-4) M), an analog of W-7 with lower affinity to calmodulin than W-7, showed weaker inhibition. Other calmodulin antagonists, such as prenylamine, chlorpromazine and compound 48/80, also inhibited the PTX-induced K+ release. These results suggest that the K+ release induced by PTX involves the process(es) mediated by intracellular Ca2+ and calmodulin.

Sugar moiety of cardiac glycosides is essential for the inhibitory action on the palytoxin-induced K+ release from red blood cells.

Palytoxin (PTX), a highly toxic and sugar-containing substance isolated from Palythoa tuberculosa, caused K+ release from rabbit red blood cells. Cardiac glycosides, such as ouabain, convallatoxin, cymarin, digoxin and digitoxin, inhibited the PTX-induced K+ release. Their corresponding aglycones did not inhibit the K+ release, but antagonized the inhibitory effect of the glycosides. All these cardiotonic steroids equally inhibited the activity of (Na+ + K+)-ATPase prepared from hog cerebral cortex. These results suggest that the sugar moiety of the cardiac glycosides is important for the inhibitory effect on the K+ release induced by PTX and that the inhibition is not related to their inhibitory potency on the (Na+ + K+)-ATPase activity.

Intracellular Ca2+-calmodulin system involved in the palytoxin-induced K+ release from rabbit erythrocytes.

Palytoxin (PTX) caused K+ release from rabbit erythrocytes which was dependent on the concentrations of extracellular Ca2+ and PTX. In a Ca2+-free solution, PTX still caused a slow K+ release. An intracellular Ca2+ antagonist, TMB-8, an intracellular Ca2+ chelator, quin 2, and calmodulin inhibitors, prenylamine, W-7 and W-5, inhibited the PTX-induced K+ release in a Ca2+-free solution. These results suggest that the PTX-induced K+ release is dependent on the process including intracellular Ca2+ and calmodulin.

Comparative effects of verapamil and sodium nitroprusside on contraction and 45Ca uptake in the smooth muscle of rabbit aorta, rat aorta and guinea-pig taenia coli.

The effects of verapamil and sodium nitroprusside on muscle tension and 45Ca uptake activated in different ways were compared in rabbit aorta, rat aorta and guinea-pig taenia coli. In rabbit aorta, K-induced contraction was specifically inhibited by verapamil and noradrenaline-induced contraction by sodium nitroprusside. In rat aorta, both K-induced and noradrenaline-induced contractions were inhibited by verapamil or by sodium nitroprusside also. In taenia, both K- and histamine-induced sustained contractions were inhibited by verapamil but not by sodium nitroprusside. The effect of verapamil was competitively antagonized by external Ca, while that of sodium nitroprusside was not. High K, noradrenaline and histamine increased the rate of 45Ca uptake in aortae and taenia. In rabbit aorta the increment in response to high K was specifically inhibited by verapamil and the increment induced by noradrenaline was specifically inhibited by sodium nitroprusside. In rat aorta, increments induced by both high K and noradrenaline were inhibited by verapamil and by sodium nitroprusside. In taenia, the increments induced by high K and by histamine were inhibited by verapamil but not by sodium nitroprusside. These results suggest different characteristics of Ca entry systems in these smooth muscles. In rabbit aorta, there seem to be two Ca channels, one of which is activated by high K and inhibited by verapamil, while the other is activated by noradrenaline and inhibited by sodium nitroprusside. In rat aorta, both K- and noradrenaline-activated Ca pathways are sensitive to both verapamil and sodium nitroprusside whereas, in taenia, both K- and histamine-activated Ca pathways are sensitive only to verapamil.

Age-related changes in the sensitivity to verapamil and sodium nitroprusside of vascular smooth muscle of rabbit aorta.

Age-related changes in the sensitivity to verapamil and sodium nitroprusside were examined in isolated aortic strips of the rabbit. In the aortae of newborn rabbits within 10 days of birth, the resting tone of the muscle was strongly reduced by sodium nitroprusside but not by either Ca-deficient solution or by verapamil. High K-induced contraction and noradrenaline-induced contraction were both inhibited by verapamil or sodium nitroprusside. In the aortae of 24 day-old rabbits, resting tension was slightly reduced by sodium nitroprusside but not by verapamil. High K-induced contraction was less sensitive to sodium nitroprusside than to verapamil whereas noradrenaline-induced contraction was less sensitive to verapamil than to sodium nitroprusside. In the aortae isolated from 60 day-old or older rabbits, resting tension was not affected by either sodium nitroprusside or verapamil. High K-induced contraction was inhibited by verapamil whereas sodium nitroprusside showed only a weak inhibitory effect. Noradrenaline-induced contraction was inhibited by sodium nitroprusside although verapamil had only a slight inhibitory effect. In the aortae of 1 day-old and also in adult rabbits, noradrenaline induced an additional increase in muscle tension when applied during the sustained contraction induced by high K. It is suggested that, in the newborn rabbit aorta, the voltage-dependent Ca channel is sensitive to both verapamil and sodium nitroprusside and the sensitivity to sodium nitroprusside gradually decreases during maturation whereas the receptor-linked Ca channel is also sensitive to both of the inhibitors at birth but the sensitivity to verapamil gradually decreases with age.

Inhibitory effects of caffeine on contractions and calcium movement in vascular and intestinal smooth muscle.

1. The mechanism of the inhibitory effect of caffeine was investigated using vascular smooth muscle of rabbit aorta and intestinal smooth muscle of taenia isolated from guinea-pig caecum. 2. Caffeine, 0.5-10 mM, relaxed the sustained contraction induced by 65.4 mM KCl or 10(-6) M noradrenaline in aorta, and by 45.4 mM KCl or 10(-6) M carbachol in taenia. The inhibitory effect of caffeine on the high K+-induced contraction was antagonized by external Ca2+ but not by the Ca2 channel activators, Bay K 8644 (10(-7) M) or CGP 28,392 (10(-7) M). Forskolin (2 x 10(-7) M) potentiated the inhibitory effect of caffeine on the noradrenaline-induced contraction but not on the high K+- or carbachol-induced contraction. Caffeine induced a time- and concentration-dependent increase in the cyclic AMP content of aorta and forskolin caused a further augmentation. 3. 45Ca2+ uptake was increased by high K+ or noradrenaline in aorta and by high K+ or carbachol in taenia. The increments were inhibited by caffeine at concentrations needed to inhibit muscle contractions. 4. 45Ca2+ in the cellular releasable site in aorta was decreased either by noradrenaline or by caffeine. Simultaneous application of noradrenaline and caffeine did not induce an additive decrease. 5. In aorta treated with a Ca2+-free solution, caffeine induced only a small contraction. Noradrenaline induced a greater contraction which was inhibited by caffeine. After washout of caffeine and noradrenaline, the second application of noradrenaline induced a transient contraction suggesting that caffeine does not deplete the noradrenaline-sensitive store. 6. It was concluded that caffeine has multiple sites of action in smooth muscle. Caffeine releases Ca2+ from a store which is apparently not sensitive to noradrenaline. Caffeine may inhibit noradrenalineinduced Ca2' release. Caffeine itself induces only a small contraction possibly because it decreases the Ca2+ sensitivity of contractile filaments and/or increases Ca2+ extrusion. Further, caffeine seems to inhibit stimulated Ca2+ influx. Cyclic AMP may be only partly responsible for the inhibitory effect of caffeine.

The inhibitory effects of N2-dansyl-L-arginine-4-t-butylpiperidine amide (TI233) on contraction of vascular and intestinal smooth muscle.

Effects of N2-dansyl-L-arginine-4-t-butylpiperidine amide (TI233) on the contractions in vascular and intestinal smooth muscles were examined. High K-induced sustained contractions in the smooth muscles were inhibited by TI233 with an IC50 of 2.1 X 10(-5) M for rabbit aorta and 3.6 X 10(-6) M for guinea-pig taenia coli in a solution containing 1.5 mM Ca. Initial transient contraction induced by K in taenia coli was less sensitive to the inhibitory effect of TI233. When the Ca concentration in the medium was decreased to 0.3 mM, the concentration-inhibition curves for TI233 shifted to the left in both aorta and taenia coli. Increasing the Ca concentration to 7.5 mM shifted the curve to the right in the aorta. TI233 also inhibited the noradrenaline-induced contraction in the aorta (IC50 = 2.1 X 10(-5 M). In a hypoxic solution without added glucose, the inhibitory effect of TI233 on the K-induced contraction in aorta was augmented. In the presence of high concentrations (40 mM) of glucose in hypoxia, TI233 did not inhibit the noradrenaline-induced contraction of the aorta. Hypoxia and a high concentration of glucose also decreased the inhibitory effect of TI233 on the K-induced contraction in taenia coli. TI233 inhibited the K-induced increase in cellular Ca content measured by a modified lanthanum method. TI233 decreased oxygen consumption and ATP content of resting and K-stimulated aorta and taenia coli. It was concluded that TI233 inhibits the vascular and intestinal smooth muscle contraction by a Ca antagonistic action and also by inhibition of aerobic metabolism.

Nitroglycerine-induced biphasic relaxation in vascular smooth muscle of rat aorta.

Nitroglycerine induced biphasic relaxation in the rat aorta, previously contracted by noradrenaline; a rapid decrease in tension was followed by a gradual increase reaching a steady level below the control contractile tension. No initial transient relaxation was induced by nitroglycerine in high K-stimulated muscle. The initial transient relaxation, but not the sustained relaxation, was dependent on the concentration of external K; maximum relaxation was observed in the presence of 2.7 mM K solution and only a slight relaxation was observed in 0 mM or 10.8 mM K solution. The initial transient relaxation was also inhibited by ouabain or low Na solution. On an appropriate increase in the concentration of external K, noradrenaline-induced contraction was transiently relaxed. Previous application of nitroglycerine potentiated this K-induced relaxation. Pretreatment of the muscle with methylene blue, an inhibitor of guanylate cyclase, inhibited both the initial transient and the sustained relaxations induced by nitroglycerine, but not the K-induced transient relaxation. It is suggested that the nitroglycerine-induced initial transient relaxation, but not the sustained relaxation, may be due to a stimulation of an electrogenic Na pump. Both relaxation phases may be mediated by cyclic GMP.

Mechanism of cadmium-induced contraction in ileal longitudinal muscle of guinea-pig.

1 The mechanism of cadmium (Cd2+)-induced contraction was studied in isolated ileal longitudinal muscle of guinea-pig. 2 CdCl2 (1x10(-8) to 1x10-4M)) caused a transient contraction which subsided within approximately 6 min of application. The contraction was reproducible and dependent on the concentration. The dose-response curve was bell-shaped. A maximal response was observed at concentrations of 5x10(-6) to 1x10(-5) M. 3 The contractile effect was inhibited to some degree at 20 degree C or by tetrodotoxin (0.1 microgram/ml), hyoscine (o.1 microgram/ml), but completely inhibited by Ca2+ -removal from the medium. 4 Cd2+ increased the output of [14C]-acetylcholine biosynthesized from [14C] by the preparation depending on the concentration. The increase terminated within the first 6 min and was reduced by tetrodotoxin (0.1 microgram/ml) or by removal of Ca2+ from the medium. 5 Both the contractile and transmitter releasing effects of Cd2+ were dependent on the concentration of external Ca2+. Strontium ions were able to replace Ca2+ -induced transmitter release. 6 It is suggested that Cd2+ contracts ileal longitudinal muscle through a release of cholinergic transmitter from the parasympathetic nerve terminals, which is dependent on external Ca2+. It also has a smaller hyoscine-resistant contractile effect, presumably due to a direct action on smooth muscle cells.

Effects of the calcium channel facilitator, CGP 28,392, on different modes of contraction in smooth muscle of rabbit and rat aortae and guinea-pig taenia caeci.

Effects of a Ca2+ channel facilitator, CGP 28,392, on smooth muscle contractions were examined in order to delineate characteristics of Ca2+ channels in rabbit and rat aortae and guinea-pig taenia caeci. Application of increasing concentrations of KCl induced contractile responses in these smooth muscles and CGP 28,392 shifted the concentration-response curve for KCl to the left. The maximum response was also increased in rat aorta and guinea-pig taenia. CGP 28,392 also shifted the concentration-response curves for noradrenaline in rat aorta and for histamine in taenia to the left and increased the maximum response in rat aorta. However, the corresponding curve for noradrenaline in rabbit aorta was not affected by CGP 28,392. The sustained contractions induced by KCl were inhibited by cumulative application of verapamil in these smooth muscles. Pretreatment of the muscle with CGP 28,392 decreased the inhibitory effect of verapamil. The noradrenaline-induced contraction in rat aorta and the histamine-induced contraction in taenia were also inhibited by verapamil, and CGP 28,392 antagonized the effect of verapamil. The noradrenaline-induced contraction in rabbit aorta was only slightly inhibited by verapamil, and CGP 28,392 did not modify the effect of verapamil. In these smooth muscles, cumulative application of Ca2+ to the Ca2+-depleted, KCl-treated muscle induced contraction, and the concentration-response curve for Ca2+ was shifted to the left by CGP 28,392 and to the right by verapamil. The concentration-response curves for Ca2+ in Ca2+-depleted, noradrenaline-treated rabbit and rat aortae and in Ca2+-depleted, histamine-treated taenia were also shifted to the left by CGP 28,392 and to the right by verapamil. In some contractions, CGP 28,392 increased and verapamil decreased the maximum responses. CGP 28,392 antagonized the inhibitory effect of verapamil. 5 These results suggest that the Ca2 channel facilitator, CGP 28,392, has a relatively selective activating effect on voltage-dependent Ca2+ channels in rabbit aorta. However, it also activates receptor-linked Ca2+ channels in rabbit aorta when Ca2+ concentrations are low. In rat aorta and guinea-pig taenia this facilitator activates both types of Ca2+ channels.

Effects of calmodulin antagonists on tension and cellular calcium content in depolarized vascular and intestinal smooth muscles.

1 Several putative calmodulin antagonists have been examined for their inhibitory action on muscle tension and cellular Ca content in the K-depolarized vascular and intestinal smooth muscles. 2 The 65.4 mM K-induced sustained contraction in the media-intimal layer of rabbit aorta and the 45.4 mM K-induced sustained contraction in guinea-pig taenia coli were inhibited by the calmodulin antagonists, prenylamine, chlorpromazine, N2-dansyl-L-arginine-4-t-butylpiperadine amide (No. 233), and N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), and also by the organic Ca antagonists, verapamil and diltiazem. 3 The cellular Ca content in rabbit aorta and guinea-pig taenia coli as measured by a modified lanthanum technique increased in the high-K solutions. The increments were inhibited by these antagonists at concentrations similar to those required to inhibit the K-induced contractions. However, W-7 did not change (in aorta) or only slightly decreased (in taenia coli) the K-induced increase in the cellular Ca content. 4 A high concentration (2 X 10(-4)M) of W-7 increased the resting cellular Ca content without increasing the muscle tension in aorta. The increment was inhibited by verapamil, sodium nitroprusside or hypoxia (N2 aeration). 5 It is suggested that the inhibitory effects of prenylamine, chlorpromazine and No. 233 may be attributed mainly to the Ca antagonistic effect whereas W-7 may inhibit the process beyond the transmembrane Ca influx.

Inhibition of calcium channels by harmaline and other harmala alkaloids in vascular and intestinal smooth muscles.

Effects of harmaline and other harmala alkaloids on the contractions induced in the vascular smooth muscle of rabbit aorta and intestinal smooth muscle of taenia isolated from guinea-pig caecum were examined. In rabbit isolated aorta, harmaline inhibited the sustained contraction induced by 65.4 mM K+ with an IC50 (concentration needed for 50% inhibition) of 4.6 X 10(-5) M. This inhibitory effect on high K+-induced contraction was antagonized by raising the concentration of external Ca2+ but not by Bay K 8644, a Ca2+ channel facilitator. Harmaline also inhibited the sustained contraction induced by noradrenaline (10(-6) M) with an IC50 of 7.6 X 10(-5) M. The inhibitory effects on noradrenaline-induced contractions were not antagonized by raising the external Ca2+ concentrations or by Bay K 8644. In guinea-pig taenia, harmaline inhibited the 45.4 mM K+-induced contraction with an IC50 of 6.8 X 10(-5) M and the carbachol (10(-6) M)-induced contraction with an IC50 of 7.0 X 10(-5) M. The inhibitory effects on both high K+- and carbachol-induced contractions were antagonized by raising the external Ca2+ concentrations but not by Bay K 8644. Harmaline, at the concentrations needed to inhibit the muscle contraction, inhibited the increase in 45Ca2+ uptake induced by high K+, noradrenaline and carbachol in aorta and taenia. Harmaline did not change the cellular Na+ and ATP contents in resting and high K+ stimulated taenia. Other harmala alkaloids also inhibited the contractions in these smooth muscles. The order of the inhibitory potency was 6-methoxyharman = harmine > harmaline = 2-methylharmine = harmane > 6-methoxyharmalan > harmalol = harmol for the contractions induced by high K+ in aorta and taenia and by carbachol in taenia, and 2-methylharmine >6-methoxyharman >6-methoxyharmalan = harmol = harmalol = harmane > harmine> harmaline for the contraction induced by noradrenaline in aorta. 7 These results suggest that harmaline inhibits the contractile response ofrabbit aorta and guinea-pig taenia by inhibiting different types of Ca2 channel. The structure-activity relationship indicates that the potency and selectivity of the inhibitory effects on these channels are varied by modification of the structure of this alkaloid.

Effects of pirarubicin, an antitumor antibiotic, on the cardiovascular system.

In the present study we examined the effects of pirarubicin [(2"R)-4'-O-tetrahydropyranyladriamycin, THP] on a cardiovascular system. An injection of THP (0.39-3.13 mg/kg, i.v.) reduced the mean blood pressure and caused an increase in the respiratory air rate in anesthetized rats. At 1.5 x 10(-6)-1.5 x 10(-5) M, THP markedly relaxed a contraction induced by 10(-7) M norepinephrine in rat aorta with endothelium but not in that without endothelium. At a dose of 0.02-0.5 mg, THP produced an increase in the contractile force and the perfusion flow of isolated perfused guinea pig hearts. At a higher concentration (4.5 x 10(-5)-1.5 x 10(-4) M), it produced a slight increase in the contractile force of the left atria in guinea pigs. This positive inotropic action of THP was inhibited by diphenhydramine (10(-6)-5 x 10(-5) M), chlorpheniramine (3 x 10(-7)-3 x 10(-5) M), and tripelennamine (3 x 10(-7)-3 x 10(-5) M) but not by propranolol (10(-6) M), cimetidine (10(-5) M), diltiazem (10(-6) M), or ryanodine (10(-8) M). THP given i.v. at 2.5 mg/kg elevated the plasma histamine level in anesthetized dogs. From these data, we conclude that THP mainly relaxed the rat aorta in the presence of endothelium and that at higher concentrations, it increased the contractile force in the cardiac muscle, probably mediated through the release of histamine.

Effects of vanadate on mechanical responses and Na-K pump in vascular smooth muscle.

The effects of vanadate on tension and on the Na-K pump in isolated guinea-pig aorta were investigated. Vanadates (NH4VO3 or Na3VO4 . nH2O) (10(-3) M) produced a sustained contraction (about 0.5 g) which was not influenced by phentolamine (10(-6) M). In the absence of external Ca, vanadate and norepinephrine (2 x 10(-6) M) induced a small contraction, although high K (45.4 mM) did not. In a Ca-depleted, high K (142.2 mM) solution, vanadate and norepinephrine still caused muscle contraction. D600 (10(-6) M) slightly inhibited the contractions induced by vanadate and norepinephrine, while this agent completely inhibited the contraction induced by high K. Sodium nitroprusside (10(-5) M) strongly inhibited the contractions induced by vanadate and norepinephrine but not the contraction induced by high K. Vanadate produced a contraction in K-free solution with ouabain (10(-4) M). The tissue K content did not change during a 2 h treatment of the muscle with vanadate. Reaccumulation of K following a 3 h treatment of the muscle with K-free solution was inhibited by ouabain but not by vanadate. These results indicate a similarity between the contractions induced by vanadate and by norepinephrine and suggest that the vanadate-induced contraction is not due to an inhibition of the Na-K pump.

Possible role of endogenous catecholamines in the contractions induced in rabbit aorta by ouabain, sodium depletion and potassium depletion.

Effects of ouabain, Na+ depletion and K+ depletion on the tension development of rabbit aorta were studied. Contraction in the strips was induced by ouabain and Na+-free solution substituted with Li+, tris or sucrose. The contractions were rarely seen under alpha-adrenergic blockade, in reserpinized aorta and mechanically denervated aorta. Contractions induced by norepinephrine were potentiated by Na+ depletion, K+ depletion and ouabain. Contractions induced by high K+ solution were also potentiated by Na+ depletion and ouabain. The potentiation in Li+ solution, K+-free solution and with ouabain was not seen under alpha-adrenergic blockade, in reserpinized aorta and denervated aorta although the potentiation by tris and sucrose solutions was still observed. These data suggest that Na+ depletion, K+ depletion and ouabain release endogenous catecholamines which affect the contraction of the vascular smooth muscle of rabbit aorta.

Comparison of the inhibitory effects of nicorandil, nitroglycerin and isosorbide dinitrate on vascular smooth muscle of rabbit aorta.

The inhibitory effects of nicorandil, nitroglycerin and isosorbide dinitrate on the contractions induced by 10(-6) M norepinephrine or by 65.4 mM K+ were compared in the vascular smooth muscle of rabbit aorta. These compounds relatively selectively inhibited the contraction induced by norepinephrine. Norepinephrine induced a sustained contraction in the aorta depolarized with high K+ and treated with 10(-6) M verapamil, and this contraction was also inhibited by these compounds. The increase in Ca2+ influx induced by norepinephrine, but not by high K+, was inhibited by the three compounds. The norepinephrine-induced transient contraction, which is due to release of stored Ca2+, was inhibited by these compounds. The inhibitory effects of nicorandil and nitroglycerin on this contraction were attenuated by high-K+ depolarization. Methylene blue (10(-5) M) antagonized and M&B 22948 (10(-5) M) potentiated the inhibitory effects of these compounds. These results suggest that nicorandil, nitroglycerin and isosorbide dinitrate have a similar mechanism of action. These compounds inhibit the norepinephrine-induced sustained contraction possibly by inhibiting the Ca2+ influx through receptor-linked Ca2+ channels, and inhibit the transient contraction by membrane hyperpolarization and also by direct inhibition of Ca2+ release although other mechanism of action may also be involved.

Effects of ouabain and potassium-free solution on the contraction of isolated blood vessels.

Ouabain and K-free solution affected the tension development of isolated vessels as follows. In rabbit aorta, ouabain induced a transient contraction followed by a delayed sustained contraction whereas K-free solution was almost ineffective; both ouabain and K-free solution produced a sustained contraction in guinea pig aorta; rat aorta rarely responded to ouabain but developed a contraction in K-free solution. Phentolamine inhibited the transient contraction produced by ouabain in rabbit aorta. In rabbit aorta, ouabain produced a concentration-dependent potentiation of norepinephrine contraction. In denervated rabbit aorta, however, the potentiation only occurred in the presence of 5 X 10(-7) to 5 X 10(-6) M ouabain. K-free solution inhibited the norepinephrine contraction in denervated rabbit aorta. Ouabain potentiated the norepinephrine contraction in guinea pig aorta but not in rat aorta. It is concluded that ouabain and K-free solution affect contraction both indirectly via the release of endogenous catecholamines and directly by acting on vascular smooth muscle, and that there are species differences in the sensitivity to ouabain.

Properties of contractions induced by ouabain and K+-free solution in guinea pig taenia coli.

The properties of contractions induced by ouabain and by K depletion were studied in comparison with those induced by other stimulants in guinea pig taenia coli. Ouabain 7.5 X 10(-6) M and K depletion produced biphasic contractions with similar time courses. Both contractions were slightly inhibited by low (0.25 mM) and high (7.5 mM) Ca concentrations, while the high K contraction was strongly inhibited by low Ca and potentiated by high Ca. Contractions induced by ouabain and K depletion were highly sensitive to lowering of the temperature and abolished at 15 degrees C, although contractions induced by carbachol 1.1 X 10(-7) M and histamine 5 X 10(-7) M were still observed below 15 degrees C. In Cl deficient solution substituted by SO4 or propionate, contractions induced by ouabain and K depletion were potentiated, while contractions induced by high K, carbachol and histamine were suppressed. These results indicate a striking similarity between contractions induced by ouabain and K depletion suggesting a common mechanism for both contractions.

Mobilization of stored calcium for phasic contraction induced by norepinephrine in rabbit aorta.

In Ca-free solution norepinephrine (NE) produced only a phasic contraction in the media-intima layer of rabbit aorta. The second application of NE was almost ineffective. Incubation of the muscle with Ca for a short period (Ca loading) restored the ability to produce a phasic contraction in Ca-free solution. Various ions and compounds were applied to the muscle prior to the Ca loading or prior to NE application and it was found that these treatments variously affected the NE-induced phasic contraction. The data suggest that the NE-induced phasic contraction in Ca-free solution results from Ca release from cellular sites and that a hyperbolic relationship exists between the amount of Ca at these sites and the magnitude of the contraction. These sites take up extracellular Ca by a process sensitive to La3+ but not to D600; the Ca influx stimulated by high K solution, which is sensitive to D600 and also contributes to refilling of these sites; NE releases this stored Ca by a process sensitive to procaine, caffeine and theophylline and, in this manner, elicits a phasic contraction.