Basal Tension Research Articles

Effect of a nucleating agent on lamellar growth in melt-crystallizing polyethylene oxide

The effects of a (non co-crystallizing) nucleating agent on secondary nucleation rate and final lamellar thickness in isothermally melt-crystallizing polyethylene oxide are considered. Small angle x-ray scattering reveals that lamellae formed in nucleated samples are thinner than in the pure samples crystallized at the same undercoolings. These results are in quantitative agreement with growth rate data obtained by calorimetry, and are interpreted as the effect of a local decrease of the basal surface tension, determined mainly by the nucleant molecules diffused out of the regions being about to crystallize. Quantitative agreement with a simple lattice model allows for some interpretation of the mechanism.

A2A and A3 receptors mediate the adenosine-induced relaxation in spontaneously active possum duodenum in vitro.

1. The aim of this study was to define the P1 purinergic receptors that regulate spontaneous or adenosine-induced duodenal motor activity. 2. Spontaneous contractile activity was recorded isometrically from possum longitudinal duodenal muscle strips. Adenosine (0.5 micro M-1 mM) was administered noncumulatively and repeated after pretreatment with a P1 antagonist or tetrodotoxin (TTX, 1 micro M), (n=4-7). Antagonists used were: A(1), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 10 nM); A(2A), 8-(3-chlorostyryl)caffeine (CSC, 10 micro M); A(2B), 3-isobutyl-8-pyrrolidinoxanthine (IPDX, 10 micro M); A(3), 9-chloro-2-(2-furanyl)-5-[(phenylacetyl) amino][1,2,4]-triazolo(1,5-c)quinazoline (MRS1220, 10 micro M). Changes in activity are expressed as percentage of baseline. Statistical analysis utilised nonparametric tests. 3. Adenosine (n=34) induced a long-lasting, concentration-dependent decrease in activity by 55.6+/-3.2% area under curve (AUC), 47.3+/-4.0% contraction amplitude, 31.6+/-3.6% basal tension and 10.4+/-1.7% contraction frequency (all P<0.001). The adenosine-induced decrease in contraction amplitude was blocked by CSC (P<0.01) or inhibited by MRS1220 (P<0.03) pretreatment, but not modified by TTX, DPCPX or IPDX pretreatment. 4. Adenosine antagonists modified spontaneous contractile activity. Pretreatment with DPCPX or CSC increased basal tension, whereas IPDX or MRS1220 pretreatment decreased contractile activity. 5. In conclusion, exogenous adenosine reduced duodenal longitudinal motor activity via A(2A) and A(3) receptors. Our findings suggest that endogenous purines may modulate spontaneous duodenal motor activity.

Octopamine modulates spermathecal muscle contractions in Locusta migratoria.

Octopamine was identified in the spermathecal tissue of Locusta migratoria using HPLC and immunohistochemical techniques. Octopamine-like immunoreactive unpaired median neurons were identified in the VIIth and VIIIth (terminal) abdominal ganglia and octopamine-like immunoreactive axons were present in the ventral ovipositor nerve (branches from this nerve innervate the spermatheca). Stimulatory actions of octopamine on myogenic and neurogenic contractions were observed. Dose-dependent increases in the frequency of myogenic contractions and the amplitude of neurogenic contractions were elicited by the application of octopamine to the spermathecal muscle. Non-sustained basal tension increases were noted in some preparations, although these were not found to be dose-dependent. SchistoFLRFamide (PDVDHVFLRFamide) inhibited octopamine-induced contractions by a maximum of about 30%. In the presence of 3-isobutyl-1 -methylxanthine, octopamine increased cAMP levels in all regions of the spermathecal. The largest increase in cAMP content was found in the spermathecal sac, followed by the straight duct and coil duct. Phentolamine blocked octopamine-induced increases in cAMP levels and abolished the actions of octopamine on myogenic contractions.

Leptin inhibits angiotensin II-induced intracellular calcium increase and vasoconstriction in the rat aorta.

Besides its role in body weight control leptin may also act as a vasoactive hormone. This study was designed to investigate whether leptin modifies angiotensin II (ANG II)-induced vascular responses. The expression of functional leptin receptors (OB-Rb) was detected in vascular smooth muscle cells (VSMCs) from adult Wistar rats by RT-PCR. Immunocytochemistry and Western blot analysis further showed the expression of OB-R protein in VSMCs. The ANG II (10(-7) mol/liter)-induced increase in intracellular Ca(2+) was blocked (P < 0.01) by leptin (10(-8) mol/liter). Moreover, in calcium-free buffer leptin was able to inhibit 65% of the ANG II-induced calcium release from intracellular stores. In endothelium-denuded aortic rings from adult Wistar rats no effect of leptin on basal tension was observed. However, the ANG II-induced isometric contraction was reduced (P < 0.05) by leptin (10(-8) mol/liter). The experiments were also performed in age- and sex-matched Zucker rats, in which no effect of leptin on ANG II-induced calcium increase and vasoconstriction was observed. It is concluded that leptin blocks the vasoconstrictor action of ANG II and inhibits the ANG II-induced increase in intracellular Ca(2+) in VSMCs through OB-Rb. These findings provide new insight into the physiological effects of leptin on blood pressure regulation.

Hypochlorous Acid Is a Potent Inhibitor of Acetylcholinesterase

The role of hydrogen peroxide and peroxynitrite in the induction of airway hyperreactivity has been well described. Another reactive species which is formed during airway inflammation is hypochlorous acid (HOCl). In the present investigation the effect of HOCl on cholinergic innervation of the airway was investigated. It was observed that HOCl was capable of increasing the basal tension of electrically stimulated tracheal smooth muscle. It was found that HOCl inhibits purified acetylcholinesterase with an IC50 value of 0.66 μM. Decreased acetylcholinesterase activity could allow accumulation of acetylcholine and increased airway muscle tension. The effects of HOCl on the isolated organ and the enzyme preparation could be precluded with thiol group-containing compounds such as reduced glutathione and N-acetylcysteine. The present findings indicate that HOCl can act as inhibitor of acetylcholinesterase. The implications of this finding for the induction of airway hyperreactivity are discussed.

C-type natriuretic peptide system in rabbit colon

C-type natriuretic peptide (CNP) is mainly distributed in the brain and vascular endothelium and is considered to act as a local regulator in many tissues. The present study was aimed to determine the presence of CNP system and its biological function in rabbit colon. The serial dilution curves of tissue extracts were parallel to the standard curve of CNP-22. With gel permeation chromatography and reverse-phase HPLC, the major immunoreactive peak of CNP was observed at the same elution time corresponding to the synthetic CNP-53. The concentration of CNP in the mucosal layer of colon was 212.49 ± 30.44 pg/g tissue wet weight ( n = 7), which was significantly higher than that in the muscular layer. The presence of CNP mRNA was also detected by RT-PCR and Southern blot analysis. Production of cGMP by the activation of particulate guanylyl cyclase stimulated by BNP and CNP was higher in membranes obtained from the muscular layer than from mucosal layer. More cGMP was produced by CNP than by ANP. Both natriuretic peptide receptor-A and -B mRNAs were detected by RT-PCR and specific binding sites to 125I-[Tyr 0]-CNP-22 were mainly localized to the muscular layer. Synthetic CNP inhibited basal tension, frequency and amplitude of basal motility of taenia coli of the right colon. This study showing the presence of CNP system and its biological function in colon suggests that endogenous CNP synthesized in the mucosal layer may have a paracrine function as a local regulator of colonic motility.

Effects of chronic estrogen-receptor blockade on ovine perinatal pulmonary circulation.

Prolonged infusions of 17beta-estradiol reduce fetal pulmonary vascular resistance (PVR), but the effects of endogenous estrogens in the fetal pulmonary circulation are unknown. To test the hypothesis that endogenous estrogen promotes pulmonary vasodilation at birth, we studied the hemodynamic effects of prolonged estrogen-receptor blockade during late gestation and at birth in fetal lambs. We treated chronically prepared fetal lambs with ICI-182,780 (ICI, a specific estrogen-receptor blocker, n = 5) or 1% DMSO (CTRL, n = 5) for 7 days and then measured pulmonary hemodynamic responses to ventilation with low- and high-fraction inspired oxygen (FI(O(2))). Treatment with ICI did not change basal fetal PVR or arterial blood gas tensions. However, treatment with ICI abolished the vasodilator response to ventilation with low FI(O(2)) [change in PVR -30 +/- 6% (CTRL) vs. +10 +/- 13%, (ICI), P < 0.05] without reducing the vasodilator response to ventilation with high FI(O(2)) [change in PVR, -73 +/- 3% (CTRL) vs. -77 +/- 4%, (ICI); P = not significant]. ICI treatment reduced prostacyclin synthase (PGIS) expression by 33% (P < 0.05) without altering expression of endothelial nitric oxide synthase or cyclooxygenase-1 and -2. In situ hybridization and immunohistochemistry revealed that PGIS is predominantly expressed in the airway epithelium of late gestation fetal lambs. We conclude that prolonged estrogen-receptor blockade inhibits the pulmonary vasodilator response at birth and that this effect may be mediated by downregulation of PGIS. We speculate that estrogen exposure during late gestation prepares the pulmonary circulation for postnatal adaptation.

Amine Metabolism: A Novel Path to Coronary Artery Vasospasm

We hypothesized that allylamine (AA) induces subendocardial necrosis in mammals via coronary artery (CA) vasospasm. Additionally, AA toxicity is likely dependent on the enzyme semicarbazide-sensitive amine oxidase (SSAO), which is highly expressed in the aorta of rats and humans. We tested whether AA or acrolein (1, 10, 100, and 1000 μM), a highly reactive product of AA metabolism by SSAO, could contract CA or thoracic aorta (TA) in vitro and if the AA effects involved SSAO. AA or acrolein produced a similar pattern of responses in both CA and TA rings at 100 and 1000 μM, including (1) increased basal tension, (2) enhanced agonist-induced contraction (hypercontractility or vasospasm), (3) remarkable, agonist-induced slow wave vasomotion (vasospasm), and (4) irreversible reduction in vessel contractility after 1 mM exposure. Endothelium-dependent acetylcholine-induced relaxation was not altered during vasospasm in either vessel. Pretreatment with the SSAO inhibitor semicarbazide (1 mM; 10 min) prevented or significantly reduced the majority of AA's effects in both CA and TA rings and inhibited 100% of the SSAO activity present in rat TA and human CA and TA. We propose a two-step model for AA induction of CA vasospasm and resultant myocardial necrosis: (1) metabolism of AA to acrolein by coronary arterial SSAO activity and (2) acrolein induction of CA vasospasm independent of endothelial injury–a novel path.

Growth kinetics in melt-crystallizing polymers: a possible role of nucleating agents

The effect of low molecular weight dopants (nucleating agents) on the basal surface tension σ e of freely growing lamellae in melt-crystallizing polymers is analyzed in terms of a statistical thermodynamic model. The latter is based on a lattice description of the basal interfacial regions developed previously for pure, compressible melt-crystallized polymers (Physica A 287 (2000) 105). Nucleant molecules diffusing out of regions being about to crystallize are responsible of a σ e reduction which practically depends only on the average nucleant concentration and (via lamellar thickness) on the undercooling at which crystallization is driven. Growth rate data obtained by calorimetry from nucleated poly(ethylene oxide) and polyethylene are well described by the theory.

RhoA/Rho-Associated Kinase Mediates Fibroblast Contractile Force Generation

The intracellular signals governing contractile force generation by non-muscle cells remain uncertain. Our aim was to test the hypothesis that the rhoA/rho-associated kinase signaling pathway is a principal mediator of contractile force generation in non-muscle cells. We measured myosin II regulatory light chain (MLC) phosphorylation and directly quantitated force generation by chicken embryo fibroblasts in the absence and presence of selective inhibitors of rhoA, and its downstream effector, rho-associated kinase. Inactivation of rhoA, with C3 transferase, inhibited serum-stimulated MLC phosphorylation and contractile force generation. Y-27632, an inhibitor of rho-associated kinase, reduced basal contractile tension, and inhibited both serum and endothelin-1 stimulated MLC phosphorylation and contractile force generation. The results of this study provide novel evidence indicating that the rhoA/rho-associated kinase signaling pathway is a principal mediator of MLC phosphorylation and consequent contractile force generation by non-muscle cells.

Alpha adrenergic activation and hemoglobin mediated contraction in the isolated rat thoracic aorta.

A primary mechanism for Hb mediated vascular contraction appears to be Hb scavenging of endothelium derive nitric oxide (NO), a potent vasodilator. In isolated rat thoracic aorta, however, Hb elicits contraction only after precontraction. The present study investigated a possible role of the alpha adrenergic activation in the Hb mediated contraction. Thoracic aortic rings harvested from normal male SD rats were prepared in a tissue bath and isometric tension changes were evaluated. In vessel rings precontracted with 50nM norepinephrine (NE), 1 microM Hb produced an additional 21.8+/-13.2% increase in tension. Pretreatment with 70nM phentolamine, an alpha adrenergic antagonist, prevented the 50nM NE induced contraction. In these vessels, subsequent treatment with 2-4 microM Hb did not elicit contraction. In vessel rings precontracted with 37mM KCl, 2 microM Hb produced an additional 21.8+/-20.1% tension increase (P<0.05). Pretreatment with phentolamine did neither prevent KCl induced contraction nor affect subsequent Hb mediated additional contraction. To test whether there is a threshold level of basal tension for Hb to trigger contraction, a group of vessel rings were passively stretched to match the tension generated by NE before Hb treatment. In these passively stretched vessel rings, Hb did not produce a significant contraction. Pretreatment with 10mM EGTA, a Ca++ chelator, significantly reduced NE induced contraction (9.7+/-5.9 vs 137.7+/-60.0%, P<0.01) but did not prevent it. EGTA also significantly reduced 2 microM Hb induced contraction (27.2+/-29.3% vs 8.9+/-7.7%, P<0.05). In contrast, pretreatment with verapamil, a Ca++ channel blocker, did not completely block NE and Hb induced contractions. In conclusion, alpha adrenergic activation is not a requisite for the Hb mediated contraction in isolated rat aortic rings. The mechanism how prior tone enhancement allows Hb mediated contraction remains unclear but results from this study suggest a factor that controls cytosolic Ca++ levels may be involved.

Pharmacological profile of T-1032, a novel specific phosphodiesterase type 5 inhibitor, in isolated rat aorta and rabbit corpus cavernosum

This study was designed to examine the pharmacological properties of T-1032 (methyl-2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate), a novel phosphodiesterase type 5 inhibitor, in isolated rat aorta and rabbit corpus cavernosum. T-1032 (3×10−11 to 3×10−7 M) caused an endothelium-dependent relaxation in the isolated rat aorta precontracted with phenylephrine, and the relaxation was accompanied by an increase in cGMP but not cAMP levels. The T-1032-induced relaxation was attenuated by NG-nitro-l-arginine methyl ester (l-NAME) (10−3 M), a nitric oxide (NO) synthase inhibitor, or 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ) (10−5 M), a guanylyl cyclase inhibitor. T-1032 (10−9, 10−8 M) produced a potentiation of the relaxation induced by sodium nitroprusside, but not of the relaxation induced by isoproterenol. In the isolated rabbit corpus cavernosum precontracted with phenylephrine, the electrical field stimulation-induced relaxation was attenuated by treatment with tetrodotoxin (10−6 M) as well as l-NAME (10−4 M). The l-NAME-inhibited relaxation was restored by treatment with l-arginine (5×10−4 M). T-1032 (10−9 to 10−6 M) and sildenafil (10−9 to 10−6 M) produced a potentiation of the electrical field stimulation-induced relaxation as well as a decrease in basal tension in a concentration-dependent manner. It was concluded that T-1032 had potentiating effects on the NO/cGMP signaling pathway in isolated tissues, probably through specific blockade of phosphodiesterase type 5. T-1032 would be a useful compound to examine the physiologic functions of phosphodiesterase type 5 in mammalian tissues.

Hyperpolarization contributes to vascular hyporeactivity in rats with lipopolysaccharide-induced endotoxic shock

We have examined the role of membrane hyperpolarization in mediating vascular hyporeactivity induced by bacterial lipopolysaccharide (LPS) in endothelial-denuded strips of rat thoracic aorta ex vivo. The injection of rats with LPS caused a significant fall of blood pressure and a severe vascular hyporeactivity to norepinephrine. The membrane potential recording showed that endotoxemia caused a hyperpolarization when compared to the control. This hyperpolarization was fully restored by methylene blue (MB; 10 μM) and partially reversed by N ω-nitro-L-arginine methyl ester (L-NAME; 0.3 mM), 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 μM), tetraethylammonium (TEA; 10 mM), charybdotoxin (CTX; 0.1 μM), or glibenclamide (GB; 10 μM), however, this hyperpolarization was not significantly affected by apamin (0.1 μM), 4-aminopyridine (4-AP; 1 mM), or Ba 2+ (50 μM). In addition, the basal tension of the tissues obtained from endotoxemic rats was enhanced by the following order: MB ≥ ODQ > TEA ≥ L-NAME ≥ CTX > GB; whereas apamin, 4-AP or Ba 2+ had no significant effects on these tissues. In contrast, none of these inhibitors had significant effects on the membrane potential or the basal tension in control tissues. Our electrophysiological results further confirmed previous studies showing that in addition to nitric oxide, the large conductance Ca 2+-activated K +-channels and ATP-sensitive K +-channels are, most likely, responsible for endotoxin-mediated hyporeactivity to vasoconstrictor agents in vascular smooth muscle.

Genistein and daidzein modulate in vitro rat uterine contractile activity

The present study investigated the effect of genistein, daidzein and estradiol on in vitro rat uterine responsiveness to oxytocin (OT) and PGF 2α or luprostiol (L). In a first experiment, animals were either sham-operated (SH; n=5), or ovariectomized (OVX; n=20) and orally treated for three months with either genistein (G; n=5; 10 μg/g BW/d) or daidzein (D; n=5; 10 μg/g BW/d) or 17α-ethinylestradiol (E; n=5; 23 μg/kg BW/d) or untreated (OVX; n=5). At necropsy, the basal uterine tension was lower in OVX, G and D than in SH, the highest value being measured in E. Oxytocin (10 −12; 10 −11 M) or PGF 2α (10 −12; 10 −9 M) induced an increase in SH, but not in OVX, E and G. In D, only the highest doses were efficient. In a second experiment, 20 intact animals were s.c. injected with either genistein (G; n=5; 10 μg/g BW) or daidzein (D; n=5; 10 μg/g BW) or estradiol benzoate (E; n=5; 23 μg/kg BW) or vehicle (C: controls; n=5), and killed 24 h later. In C and E, OT (10 −15 to 10 −10 M) or L (10 −12 to 10 −7 M) stimulated uterine contractile activity in a dose-dependent manner until a maximal level. On the opposite, in G and D, contractile agents (except the highest luprostiol doses) did not stimulate myometrium contractions. Moreover, radioligand binding assays showed that genistein or daidzein inhibited the specific binding of [ 3H] estradiol to the calf uterus estrogen receptor (ER). Therefore, it could be postulated that both genistein and daidzein might bind to the rat uterus ER, inducing either anti-estrogenic or very weak estrogenic effects (depending on the experimental conditions) on in vitro uterine responsiveness to OT and PGF 2α or luprostiol.

A simple lattice model for the basal interface in compressible semi-crystalline polymers

The basal interfacial regions of the laminar crystalline structures growing at moderate undercoolings in melt-crystallizing polymers, are modeled by accommodating a linear chain in a cubic lattice. The model extends previous treatments in that a finite compressibility is also accounted for. It is found that, due to the presence of density gradients: (a) compressibility is responsible of order 10% contributions to the overall basal surface tension, σ e , in realistic conditions, and (b) the corresponding tight folding energies required to match the observed values of σ e decrease by order 30%.

Hypocapnic constriction in rabbit basilar artery in vitro: triggering by serotonin and dependence on endothelin-1 and alkalosis

This study tested whether hypocapnic constriction of the rabbit basilar artery in vitro can be triggered by serotonin, and whether the resulting constriction is (1) due to the alkaline pH associated with hypocapnia, and (2) endothelin-1 mediated. Hypocapnic alkaline solution (25 mM NaHCO 3; pH 7.76; pCO 2 14.2) or isocapnic alkaline solution (50 mM NaHCO 3; pH 7.73; pCO 2 35.0) rarely altered basal tension. Serotonin (3 μM) challenge in hypocapnic or isocapnic alkaline solution resulted in near maximal tension. Washout of the serotonin did not decrease tension in 54% of the tissues, as plateau tension was maintained for 2–2.5 h. The plateau tension of washed tissues was relaxed by 1–3 μM PD145065 (Ac- d-Bhg- l-Leu-Asp- l-Ile- l-Ile- l-Trp), BQ610 (homopiperidinyl-CO-Leu- d-Trp(CHO)- d-Trp), and BQ788 ( N- cis-2,6-dimethyl-piperidinocarbonyl- l-γ-MeLeu- d-Trp (COOCH 3)-Nle), endothelin ET A/ET B, endothelin ET A, and endothelin ET B receptor antagonists, respectively. In contrast, serotonin-induced tension in normal solution (25 mM NaHCO 3; pH 7.42; pCO 2 36.9) was maintained for only 40 min (mean). These results demonstrate that (1) constriction due to hypocapnia in vitro can be triggered by serotonin and is endothelin-1 mediated and (2) alkaline pH in the absence of decreased pCO 2 is sufficient to elicit the constriction triggered by serotonin.

Potentiating effects on contractions by purified baicalin and baicalein in the rat mesenteric artery.

The effects of purified baicalin and baicalein from the traditional Chinese herb, Huangqin, on contractions induced by phenylephrine, U46619, and high extracellular K+ were investigated in isolated rat mesenteric arteries. Both baicalin (1-100 microM) and baicalein (1-50 microM) potentiated the contractile response to phenylephrine in a concentration-related manner. Both flavonoids (10 microM) also enhanced the U46619- or 40 mM K+-induced contractions. Baicalein (100-300 microM) reduced the phenylephrine-induced tone. Prazosin at 1 microM did not affect U46619-induced contraction in the absence and presence of baicalein or baicalin. Neither baicalin (1-100 microM) nor baicalein (1-100 microM) affected the basal tension. Removal of the functional endothelium abolished the potentiating effects of baicalin and baicalein in arteries preconstricted by both constrictors. Pretreatment of endothelium-intact rings with 100 microM N(G)-nitro-L-arginine also potentiated phenylephrine- or U46619-induced contraction but completely inhibited the effects of baicalin and baicalein. Pretreatment with 1 mM L-arginine reversed the enhancing effect of baicalin but not of baicalein on phenylephrine-evoked contraction. Pretreatment with 10 microM baicalin or 10 microM baicalein significantly reduced the endothelium-dependent relaxation induced by acetylcholine or ionomycin. These results indicate that both baicalin and baicalein potentiated the evoked contractile response, likely through inhibition of nitric oxide formation and/or release in the endothelium.

Hypocapnic constriction in rabbit basilar artery in vitro: triggering by NG-monomethyl- l-arginine monoacetate and dependence on endothelin-1 and alkalosis

This study tested whether hypocapnic constriction of the rabbit basilar artery in vitro can be triggered by a nitric oxide (NO) synthase inhibitor, and whether the resulting constriction is (1) due to the alkaline pH associated with hypocapnia, and (2) endothelin-1 mediated. Hypocapnic (25 mM NaHCO 3; pH 7.76; pCO 2 14.2) or isocapnic alkaline solution (50 mM NaHCO 3; pH 7.73; pCO 2 35.0) rarely altered basal tension. N G-monomethyl- l-arginine monoacetate (L-NMMA; 0.1 mM) challenge in hypocapnic or isocapnic alkaline solution resulted in near maximal tension that was maintained for 2–2.5 h even following L-NMMA washout. L-NMMA challenge in normal solution (25 mM NaHCO 3; pH 7.42; pCO 2 36.9) also induced near maximal tension, although the tension was maintained for only 25 min (mean). Ac- d-Bhg- l-Leu-Asp- l-Ile- l-Ile- l-Trp (PD145065), homopiperidinyl-CO-Leu- d-Trp(CHO)- d-Trp (BQ610), and N- cis-2,6-dimethyl-piperidinocarbonyl l-γ-MeLeu- d-Trp (COOCH 3)-Nle (BQ788; 1–3 μM), endothelin ET A/ET B, endothelin ET A, and endothelin ET B receptor antagonists, respectively, completely relaxed the tension that resulted from L-NMMA challenge in hypocapnic or isocapnic alkaline solution. These results demonstrate that constriction due to hypocapnia in vitro can be triggered by an NO synthase inhibitor and is endothelin-1 mediated. Additionally, alkaline pH in the absence of decreased pCO 2 is sufficient to elicit the constriction.

Thiopental induces contraction of rat aortic smooth muscle through Ca(2+) release from the sarcoplasmic reticulum.

Little is known about the mechanism of thiopental-induced contraction in vascular smooth muscle. This study aimed to clarify this question by conducting isometric tension experiments and (45)Ca(2+) flux measurements in endothelium-denuded rat aortic rings. Thiopental induced a concentration-dependent contraction under basal tension. This contraction was enhanced when rings were precontracted with phenylephrine in the presence of verapamil. In Ca(2+)-free solution, thiopental-induced contraction was reduced but not abolished with high concentrations. Ca(2+) store depletion with a maximum dose of caffeine in Ca(2+)-free solution further reduced the contraction by subsequent thiopental. Ca(2+) store depletion with thapsigargin completely abolished contraction by thiopental. (45)Ca(2+) influx experiment in the presence of verapamil showed that thiopental could not induce any Ca(2+) influx with or without phenylephrine prestimulation. The (45)Ca(2+) efflux experiment showed more evidence of thiopental-induced Ca(2+) release, which was abolished by thapsigargin. In conclusion, thiopental induces contraction in rat aortic smooth muscle by releasing Ca(2+) from the sarcoplasmic reticulum without Ca(2+) influx. This is the first study providing evidence that thiopental-induced vascular contraction is caused by Ca(2+) release from the sarcoplasmic reticulum of the smooth muscle.

Thiopental Induces Contraction of Rat Aortic Smooth Muscle Through Ca2+ Release from the Sarcoplasmic Reticulum

Little is known about the mechanism of thiopental-induced contraction in vascular smooth muscle. This study aimed to clarify this question by conducting isometric tension experiments and 45Ca2+ flux measurements in endothelium-denuded rat aortic rings. Thiopental induced a concentration-dependent contraction under basal tension. This contraction was enhanced when rings were precontracted with phenylephrine in the presence of verapamil. In Ca2+-free solution, thiopental-induced contraction was reduced but not abolished with high concentrations. Ca2+ store depletion with a maximum dose of caffeine in Ca2+-free solution further reduced the contraction by subsequent thiopental. Ca2+ store depletion with thapsigargin completely abolished contraction by thiopental. 45Ca2+ influx experiment in the presence of verapamil showed that thiopental could not induce any Ca2+ influx with or without phenylephrine prestimulation. The 45Ca2+ efflux experiment showed more evidence of thiopental-induced Ca2+ release, which was abolished by thapsigargin. In conclusion, thiopental induces contraction in rat aortic smooth muscle by releasing Ca2+ from the sarcoplasmic reticulum without Ca2+ influx. Implications This is the first study providing evidence that thiopental-induced vascular contraction is caused by Ca2+ release from the sarcoplasmic reticulum of the smooth muscle.