dinoprost and barium-chloride

Although inward rectifier K+ channels contribute to the regulation of cerebral circulation, dilation of cerebral microvasculature mediated by these channels has not been demonstrated in chronic hypertension. We designed the present study to examine the roles of inward rectifier K+ channels in the vasodilation produced by increased levels of extracellular K+ in cerebral parenchymal arterioles from hypertensive and normotensive rats. During constriction to prostaglandin F2alpha (5 x 10(-7) M), the arterioles within brain slices were evaluated using computer-assisted microscopy. Potassium chloride (KCl) induced vasodilation in cerebral arterioles from normotensive (5-10 mM) and hypertensive (5-15 mM) rats, whereas an inward rectifier K+ channel antagonist barium chloride (BaCl2; 10(-5) M) completely abolished the vasodilation in both strains. In arterioles of hypertensive rats, vasodilator responses to KCl were augmented compared with those in normotensive rats. In contrast, the vasodilator responses induced by sodium nitroprusside (3 x 10(-8) to 3 x 10(-6) M) in these two strains were similar. These results suggest that in cerebral cortex parenchymal microvessels, inward rectifier K+ channels play a crucial role in vasodilation produced by extracellular K+ and that the dilation of cerebral arterioles via these channels is augmented in chronic hypertension.

Topics: Animals; Arterioles; Barium Compounds; Blood Pressure; Brain; Cerebrovascular Circulation; Chlorides; Dinoprost; Dose-Response Relationship, Drug; Hypertension; Male; Nitroprusside; Potassium Channels, Inwardly Rectifying; Potassium Chloride; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasoconstriction; Vasoconstrictor Agents; Vasodilation

Present study was conducted on prostaglandin F2alpha (PGF2alpha), oxytocin, (OT), potassium chloride (KCI) and barium chloride (BaCl2) pre-contracted perimetrial uterine strips of dioestrus and pregnant buffaloes to evaluate the tocolytic efficacy of selective beta2 adrenoceptor agonists-albuterol (salbutamol) and terbutaline. Cumulative concentration-response curves of both the beta2 adrenoceptor agonists were constructed and the mean effective concentration (EC50) values determined and compared statistically. Based on the comparative EC50 values in relaxing the pre-contracted uterine strips with different spasmogens, the rank order potency of albuterol was found to be--PGF2alpha > BaCl2 > OT > KCl on uterine strips from dioestrus animals, while OT> BaCl2> PGF2alpha >KCl on the uterine strips of pregnant buffaloes. The rank order potency of terbutaline on uterine strips from dioestrus stage animals was- BaCl2 > OT > KCl > PGF2alpha, while BaCl2 > PGF2alpha > KCl > OT on uterine tissues of pregnant animals. Thus, irrespective of the state of uterus, whether gravid or non-gravid, KCl-depolarized uterine tissues required comparatively higher concentrations of albuterol or terbutaline to produce tocolytic effect. High concentrations of K+ in biophase may have interfered with the beta2 adrenoceptor agonists-induced outward K+ current and hyperpolarization. From the results of present study, it was evident that selective beta2 adrenergic agonists had good tocolytic efficacy on the uterus of buffaloes. Further, indirectly the possibility of existence and activation of K(Ca) channels by selective beta2 adrenoceptor agonists in mediating tocolysis of buffalo myometrium can not be ruled out, however, detailed studies using specific K(Ca) channel blockers are required for characterizing the nature of such channels in buffalo uterus.

Topics: Abortifacient Agents, Nonsteroidal; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Albuterol; Animals; Barium Compounds; Buffaloes; Chlorides; Dinoprost; Female; Oxytocin; Potassium Chloride; Pregnancy; Receptors, Adrenergic, beta-2; Terbutaline; Tocolytic Agents; Uterine Contraction; Uterus

Three cases of disopyramide-induced urinary retention were reported and effects of disopyramide on agonist-induced contraction of detrusor muscle were studied in vitro. Muscle strips were obtained from rabbit bladder body and changes in isometric contraction of the strips were monitored. Acetylcholine, prostaglandin F2-alpha, potassium chloride, barium chloride, adenosine triphosphate and Ca2+ were used as agonists for detrusor muscle contraction. Disopyramide relaxed the contraction elicited by acetylcholine in normal Krebs solution, but exhibited no relaxing effect on contractions induced by prostaglandin F2-alpha, potassium chloride, barium chloride and adenosine triphosphate. In Ca2+-free Krebs solution, basal tension of the strips declined and spontaneous contractile activity was eliminated. Replenishment of 3 mM Ca2+ induced a slow contraction and redevelopment of spontaneous contraction of the strips. Pretreatment of the strips with disopyramide had no inhibitory effect on the Ca2+-induced contraction or on the spontaneous contractile activity in Ca2+-free solution. In normal Krebs solution, acetylcholine (10(-9)-10(-2)M) caused dose-dependent contractions of the detrusor muscle strips. Pretreatment of the strips with disopyramide (10(-5)-10(-3)M) dose-dependently inhibited the acetylcholine-induced contraction in a competitive way. The inhibitory effect of disopyramide on acetylcholine-induced contraction was less potent than that of atropine. We conclude that disopyramide may inhibit detrusor contractile activity mostly by its anticholinergic effect, resulting clinically in micturition disturbance.

Topics: Acetylcholine; Adenosine Triphosphate; Aged; Aged, 80 and over; Animals; Barium; Barium Compounds; Chlorides; Dinoprost; Disopyramide; Female; Humans; Male; Muscle Contraction; Potassium Chloride; Prostaglandins F; Rabbits; Urethral Stricture

Using a cannula-insertion method for isolated arteries, the effects of thiopental, barium chloride, and prostaglandin F2 alpha were investigated on isolated canine mesenteric arteries with and without saponin treatment. Thiopental caused a vasoconstriction in a dose-related manner. The observed vasoconstriction was not influenced by phentolamine in doses which inhibited norepinephrine-induced vasoconstriction. After intraluminal saponin treatment, thiopental- and barium chloride-induced constrictions were significantly enhanced, but prostaglandin F2 alpha-induced constriction was not potentiated. It is suggested that vasoconstrictor responses to thiopental and barium chloride may be enhanced by an increase in calcium influx after disrupting the endothelium of the artery.

Topics: Animals; Barium; Barium Compounds; Chlorides; Dinoprost; Dogs; Drug Synergism; Endothelium; Female; Injections, Intra-Arterial; Male; Mesenteric Arteries; Norepinephrine; Phentolamine; Potassium Chloride; Prostaglandins F; Saponins; Thiopental; Vasoconstriction

Mepacrine is a potent inhibitor of uterine contractile responses in vitro. Pretreatment of isolated rat uterine horns with mepacrine (1.3 X 10(-4)M) for periods of time ranging from 15 s to 5 min prior to the addition of carbachol (1.0 X 10(-4)M) showed that mepacrine could significantly reduce carbachol-induced uterine contractile responses within 15 s of exposure. The maximal inhibitory effects of mepacrine on uterine contractile responses were observed within 2 min of mepacrine treatment. A dose-response study related to the effect of increasing concentrations of mepacrine (7.5 X 10(-6) to 1.3 X 10(-4)M) on carbachol-induced (1 X 10(-4)M) uterine contractions revealed that a dose of 3.1 X 10(-5)M mepacrine reduced the carbachol-induced contraction by 50%. A dose of 7.8 X 10(-5)M mepacrine produced the maximal inhibitory effect on the carbachol-induced uterine contractions. Two doses of mepacrine (3.1 X 10(-5) and 1.3 X 10(-4)M) significantly reduced maximal contractile responses and shifted contractile dose-response curves of carbachol, oxytocin, prostaglandin F2 alpha, and BaCl2 to the right. Based on the nonselective inhibition by mepacrine of contractile responses induced by different uterotonic agents, these results suggest that mepacrine cannot be used to characterize the role of phospholipase in regulating the actions of hormones in uterine tissue.

Topics: Animals; Barium; Barium Compounds; Carbachol; Chlorides; Dinoprost; Dose-Response Relationship, Drug; Female; Oxytocin; Prostaglandins F; Quinacrine; Rats; Rats, Inbred Strains; Uterine Contraction

Although calcium antagonists such as verapamil are used primarily in cardiovascular disease, they appear to relax smooth muscle generally. Therefore, the possibility that verapamil might have bronchodilator properties was explored using the guinea-pig tracheal ring technique. Verapamil was found to produce considerable tracheal smooth muscle relaxation from a threshold concentration of 2 X 10(-7) M and with maximum effect at 10(-3) M. The responses to the contractile agonists histamine and prostaglandin F2 alpha and especially methacholine and serotonin were substantially reduced by prior administration of verapamil. Verapamil 2 X 10(-4) M was equally effective as isoprenaline 10(-8) M in producing 50% maximum direct relaxation but was more effective than isoprenaline as an antagonist of the contractile agonists, methacholine, histamine and serotonin, but not prostaglandin F2 alpha. Verapamil abolished the contractile responses to barium chloride. It is concluded that, although verapamil was not very potent as a direct bronchodilator, it could potentially be of prophylactic benefit in asthma because of its efficacy as an antagonist of common contractile agonists.

Topics: Animals; Barium; Barium Compounds; Bronchi; Chlorides; Dinoprost; Dose-Response Relationship, Drug; Guinea Pigs; Histamine; Isoproterenol; Methacholine Chloride; Methacholine Compounds; Muscle Relaxation; Muscle, Smooth; Prostaglandins F; Serotonin; Verapamil

We have studied the effects of ketotifen (Ke), an effective antiallergic drug, on guinea pig trachea. Ke (10(-6)-5 X 10(-5) M) inhibits contractions induced in this preparation by acetylcholine, prostaglandin F2 alpha, barium chloride, potassium chloride and electrical stimulation. These results provide evidence for protective effects of Ke in airways. Furthermore, Ke exerts also a neural inhibitory effect on postganglionic parasympathetic fibers of guinea pig trachea. These findings resemble the effects reported previously for disodium cromoglycate by us and might be relevant for antiasthmatic and antiallergic properties of Ke.

Topics: Acetylcholine; Animals; Barium; Barium Compounds; Chlorides; Dinoprost; Electric Stimulation; Guinea Pigs; In Vitro Techniques; Ketotifen; Male; Muscle Contraction; Potassium Chloride; Prostaglandins F; Trachea

Dose-response curves for several prostaglandins (PGI2; PGD2; PGF2 and PGE2); BaCl2 or prostaglandin metabolites (15-keto-PGF2 alpha; 13,14-diOH-15-keto-PGF2 alpha; 6-keto-PGF1 alpha and 6-keto PGE1 in quiescent (indomethacin-treated) uterine strips from ovariectomized rats, were constructed. All PGs tested as well as BaCl2, triggered at different concentrations, evident phasic contractions. Within the range of concentrations tested the portion of the curves for the metabolites of PGF2 alpha was shifted to the right of that for PGF2 alpha itself; the curve for 6-keto-PGF1 alpha was displaced to the right of the curve for PGI2 and that for 6-keto-PGE1 to the left. It was also demonstrated that the uterine motility elicited by 10(-5) M PGF2 alpha and its metabolites was long lasting (more than 3 hours) and so it was the activity evoked by PGI2;6-keto-PGF1 alpha and BaCl2, but not the contractions following 6-keto-PGE1, which disappeared much earlier. The contractile tension after PGF2 alpha; 15-keto-PGF2 alpha; 13,14-diOH-15-keto-PGF2 alpha and PGI2, increased as time progressed whilst that evoked by 6-keto-PGF1 alpha or BaCl2 fluctuated during the same period around more constant levels. The surprising sustained and gradually increasing contractile activity after a single dose of an unstable prostaglandin such as PGI2, on the isolated rat uterus rendered quiescent by indomethacin, is discussed in terms of an effect associated to its transformation into more stable metabolites (6-keto-PGF1 alpha, or another not tested) or as a consequence of a factor which might protects prostacyclin from inactivation.

Topics: Animals; Barium; Barium Compounds; Castration; Chlorides; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Epoprostenol; Female; Indomethacin; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Uterine Contraction

Ketotifen (Ke) at the concentration of 10(-5) M or greater significantly inhibits guinea pig ileum contractions induced by cumulative dose response curves to Pg alpha F2 or BaCl2. This inhibitory effect of Ke is also observable against ileal contractions induced by isotonic and hypertonic solutions with high K+ and by electrical stimulation. In contrast to the long term antihistaminic effect of DSCG and Ke, the latter drug exhibits a shorter inhibitory effect when Ach and electrical stimulation are used to induce ileal contractions shortly after Ke is removed by washing from the organ bath. This nonspecific protective effect of Ke on smooth muscle against various spasmogens resembles the one reported recently by us for DSCG and might be relevant to the antiallergic and antiasthmatic properties of both drugs.

Topics: Acetylcholine; Animals; Barium; Barium Compounds; Chlorides; Cromolyn Sodium; Dinoprost; Electric Stimulation; Guinea Pigs; Ileum; In Vitro Techniques; Ketotifen; Male; Muscle Contraction; Muscle, Smooth; Potassium; Prostaglandins F

1-(2,6-Dimethylphenyl)-3-methylamidinourea hydrochloride (lidamidine hydrochloride) has previously been reported to inhibit intestinal smooth muscle contractile activity in vivo and in vitro. This study showed lidamidine also inhibited contractile activity in the isolated gravid rat uterus preparation and antagonized, the spasmogenic effects of acetylcholine, serotonin, oxytocin, and PGF2 alpha and BaCl2. Increasing Ca2+ concentrations in the bathing medium from 0.9 mmol/l to 7.2 mmol/l effectively antagonized the lidamidine inhibition of responses to BaCl2 and acetylcholine in the gravid rat uterus preparation. These results suggest that the spasmolytic effect of lidamidine may be due to its interference with the availability of Ca2+ necessary for excitation-contraction coupling in smooth muscle.

Topics: Acetylcholine; Animals; Barium; Barium Compounds; Calcium; Chlorides; Dinoprost; Female; In Vitro Techniques; Oxytocin; Parasympatholytics; Phenylurea Compounds; Prostaglandins F; Rats; Rats, Inbred Strains; Uterine Contraction