Tension Of Strips Research Articles

Low temperature decreased basal tension in isolated rat tongue

The tongue is a complex organ that plays a vital role in the functions of mastication, deglutition, articulation, airway protection, and oral hygiene maintenance. The tongue also has the function of regulating body temperature. The aim of this study was to evaluate the effect of temperature on the tension changes of isolated rat tongue, with or without electric field stimulation (EFS). Tissue bath for isolated tongue was used. An in vitro isometric contraction of tongue from healthy Sprague-Dawley rat (body weight > or =200 g) was continuously recorded. Tension in strips of rat tongues that were untreated and treated with EFS, was recorded continuously in stepwise manner in temperatures that varied from 37 to 7 degrees C or 7 to 37 degrees C. Descent and reascent of temperature produced temperature-dependent tension changes. Basal tension of the tongue decreased as temperature was reduced, while EFS-induced spike contraction increased as temperature was reduced. Low temperature induced rapid and reproducible relaxation in isolated rat tongue strip. Increasing temperature enhanced basal tension and reduced EFS-induced spike contraction of the tongue.

Effect of hyperthermia on the function of thyroid gland

Hyperthermia may be a consequence of environmental conditions, bacterial or viral infections and/or thyroid storm. This study investigates the acute effect of body temperature elevation on thyroid function and on its scintigraphy studies. Thyroid scintigraphy was performed on New Zealand White rabbits weighing approximately 3-3.5 kg. Each rabbit was injected with 115 MBq (3.1 mCi) technetium-99 m pertechnetate ((99m)Tc pertechnetate). Studies were performed using Gamma camera equipped with a low energy, high resolution, pinhole collimator interfaced with a computer. Static images were acquired 20 min after administration of the radiotracer. Two days later the same protocol was repeated for the same rabbit after increasing the body temperature by 2 degrees C. The experiment was repeated again after a 2-day interval at 3 degrees C, and then after another 2-day interval at 4 degrees C. Plasma free thyroxine (FT(4)), free triiodothyronine (FT(3)) and thyroid stimulating hormone (TSH) were measured at control and at different hyperthermic temperatures (+2, 3, 4 degrees C). We recorded isometric tension of rabbit thyroid artery strips in organ baths during stepwise temperature elevation. During hyperthermia the decrease in thyroid function and thyroid scintigraphy studies was proportional to body temperature elevation. The recording of isometric tension in rabbit thyroid artery strips in organ baths showed vasoconstriction during hyperthermia which is proportional to the heating temperature. Plasma FT(4) and FT(3) level were decreased while TSH levels were not affected by acute fever. Our results indicate that hyperthermia causes a transient decrease in thyroid gland function and scintigraphic patterns on radionuclide studies. Thus, body temperatures must be measured before radionuclide studies in order to ensure that interpretation of data is not influenced by hyperthermia.

Dihydrotestosterone and progesterone relax female guinea pig gallbladder strips

We demonstrated that dihydrotestosterone (DHT) and progesterone (P) relaxed cholecystokinin octapeptide (CCK) induced tension in male guinea pig strips; however, the effects of DHT and P on female guinea pig strips has not been fully studied. An in vitro technique was used. Statistical analyses used either paired t‐test or analysis of variance. DHT, P, 17‐hydroxyprogesterone (17‐P) or 20α–hydroxyprogesterone (20‐P; 10 μM 50 μM, and 100 μM) were used to generate concentration response curves. All 4 agents induced a concentration dependent relaxation of CCK‐induced tension. There was no significant difference between the P‐ and 17‐P‐induced relaxations. 20‐P induced significantly (P<0.05) less relaxation than P. DHT produced a relaxation similar to that induced by P and 17‐P. The relaxation caused by 50 μM and 100 μM DHT were not significantly different (63.7±5.1 vs. 63.5±6.5%). The response to 100 μM DHT was significantly less (p<0.01) than 100 μM P (91.0±6.2%). To determine if the PKA/cAMP second messenger system mediated the P‐ or DHT‐induced relaxation, PKA inhibitor 14‐22 amide myristolated (PKA‐IM; 180 nM) was used. PKA‐IM caused a significant (p<0.05) decrease in P‐induced relaxation (73.5±7.9 vs. 64.2±7.0%), but had no significant effect on DHT‐induced relaxation. When the PKC inhibitors bisindolymaleimide IV (0.5 μM) and chelerythrine Cl (5 μM) were used together, a significant (P<0.05) reduction in both P‐ and DHT‐induced relaxation (P, 56.8±4.0 vs. 36.8±6.2%; DHT, 53.0±6.3 vs. 42.5±5.1%) was observed. The results suggest that both the PKA/cAMP and PKC second messenger systems mediated the P‐induced relaxation of CCK‐induced tension in female guinea pig gallbladder strips. Only the PKC system mediates the DHT‐induced relaxation.

Antioxidant Treatment with .ALPHA.-Tocopherol Improves Erectile Function in Hypertensive Rats

There is no known treatment for erectile dysfunction (ED) in hypertensive patients. We tested whether or not antioxidative therapy improves ED in the setting of hypertension. Spontaneously hypertensive rats (SHRs) were treated with a control chow or an alpha-tocopherol-enriched chow (12 or 24 mg/100 g chow) for 8 weeks. The isometric tension of corpus cavernosum strips from these SHRs was recorded. nNOS and HO-2 gene expression and NOx, cGMP, thiobarbituric acid-reacting substance (TBARS), and superoxide dismutase (SOD) activity levels were determined in serum and tissue. Relaxation in response to electrical field stimulation (EFS) in the corpus cavernosum increased after the administration of alpha-tocopherol at a dose of 24 mg/100 g chow. This effect was inhibited by a nitric oxide synthase (NOS) inhibitor and by a heme oxygenase (HO) inhibitor, nNOS and HO-2 gene expression and NOx concentrations in the corpus cavernosum were similar between 24 mg alpha-tocopherol-fed SHRs and controls. Tissue cGMP levels were greater in alpha-tocopherol-fed SHRs than in controls. Treatment with 24 mg alpha-tocopherol decreased TBARS levels and increased SOD activity in the serum and corpus cavernosum. Relaxation in response to acetylcholine chloride in the corpus cavernosum was improved with alpha-tocopherol treatment at each dose. These results suggest that alpha-tocopherol treatment increases the diminished relaxation in the corpus cavernosum of SHRs by improving neuronal or endothelial function related to nitric oxide and carbon monoxide. This, in turn, indicates that antioxidant therapy may play a role in treatment for ED in hypertensive patients.

The Differential Effects of Intravenous Anesthetics on Myofilament Ca2+ Sensitivity in Pulmonary Venous Smooth Muscle

Pulmonary venous contraction can increase pulmonary capillary pressure and pulmonary edema. In the present study, we investigated the direct effects of ketamine, etomidate, thiopental, and midazolam on pulmonary venous contraction and myofilament Ca2+ sensitivity in permeabilized pulmonary venous smooth muscle (PVSM). The effects of these IV anesthetics on acetylcholine contraction were assessed in isolated canine pulmonary vein rings. Tension and [Ca2+]i were measured simultaneously in fura-2 loaded endothelium-denuded PVSM strips after being permeabilized with alpha-toxin. The effects of the IV anesthetics on tension ([Ca2+]i remains constant) in the absence or the presence of muscarinic receptor activation (acetylcholine) were assessed. The immunofluorescence technique and confocal microscopy were used to localize the cellular distribution of protein kinase C (PKC) isoforms in PVSM cells before and after the addition of ketamine. Ketamine, etomidate, and midazolam each attenuated acetylcholine contraction dose-dependently, whereas thiopental had no effect. None of the IV anesthetics alone had an effect on tension in strips at constant [Ca2+]i (i.e., they had no direct effect on myofilament Ca2+ sensitivity). Acetylcholine increased tension by 56% +/- 7% at constant [Ca2+]i. In acetylcholine-stimulated strips, etomidate, midazolam, and thiopental had no additional effect on tension at constant [Ca2+]i, whereas ketamine decreased tension by 33% +/- 3%. Activation with acetylcholine induced translocation of PKC from cytoplasm to membrane, and this effect was blocked by ketamine. Ketamine, etomidate, and midazolam each attenuated acetylcholine-induced pulmonary venous contraction. Ketamine attenuates acetylcholine contraction by inhibiting the acetylcholine-induced increase in myofilament Ca2+ sensitivity and the acetylcholine-induced translocation of PKCalpha.

Non‐genomic effects of androgens on isolated human vascular and nonvascular penile erectile tissue

To evaluate non-genomic effects of testosterone and dihydrotestosterone (DHT) on isolated human cavernosal arteries (HCA) and corpus cavernosum (HCC) using organ-bath studies and radio-immunoassays (RIA), as non-genomic effects of androgens are reported for vascular smooth musculature and there is evidence that the relaxant response involves a modulation of cyclic nucleotide tissue levels. The relaxation induced by the cumulative addition of testosterone and DHT (0.01-10 microm) was studied using circular segments of HCA and strip preparations of HCC. To evaluate the effects of testosterone and DHT on tissue levels of cAMP and cGMP, specimens were exposed to increasing concentrations of the hormones. Forskolin and sodium nitroprusside (SNP) served as reference compounds. Testosterone and DHT dose-dependently reversed the noradrenaline-induced tension of vascular segments and HCC strips. At the maximum concentration, testosterone and DHT reduced the mean (sd) tension to 79.8 (4.43)% and 83.9 (10.94)%, respectively. SNP and forskolin significantly stimulated the production of cGMP and cAMP. No effects of testosterone and DHT on cGMP and cAMP levels were detected. Rapid androgen-induced relaxation of HCA and HCC occurs via non-genomic mechanisms. In penile erectile tissue, non-genomic relaxant effects of testosterone and DHT are not mediated via modulation of cyclic nucleotide tissue levels. Additional studies are required to establish if non-genomic relaxant effects are important in ensuring a basal level of perfusion to maintain overall penile function.

Urocortin I is present in the enteric nervous system and exerts an excitatory effect via cholinergic and serotonergic pathways in the rat colon

Corticotropin-releasing factor (CRF) and urocortin I (UcnI) have been shown to accelerate colonic transit after central nervous system (CNS) or peripheral administration, but the mechanism of their peripheral effect on colonic motor function has not been fully investigated. Furthermore, the localization of UcnI in the enteric nervous system (ENS) of the colon is unknown. We investigated the effect of CRF and UcnI on colonic motor function and examined the localization of CRF, UcnI, CRF receptors, choline acetyltransferase (ChAT), and 5-HT. Isometric tension of rat colonic muscle strips was measured. The effect of CRF, UcnI on phasic contractions, and electrical field stimulation (EFS)-induced off-contractions were examined. The effects of UcnI on both types of contraction were also studied in the presence of antalarmin, astressin2-B, tetrodotoxin (TTX), atropine, and 5-HT antagonists. The localizations of CRF, UcnI, CRF receptors, ChAT, and 5-HT in the colon were investigated by immunohistochemistry. CRF and UcnI increased both contractions dose dependently. UcnI exerted a more potent effect than CRF. Antalarmin, TTX, atropine, and 5-HT antagonists abolished the contractile effects of UcnI. CRF and UcnI were observed in the neuronal cells of the myenteric plexus. UcnI and ChAT, as well as UcnI and 5-HT, were colocalized in some of the neuronal cells of the myenteric plexus. This study demonstrated that CRF and UcnI act on the ENS and increase colonic contractility by enhancing cholinergic and serotonergic neurotransmission. These peptides are present in myenteric neurons. CRF and, perhaps, to a greater extent, UcnI appear to act as neuromodulators in the ENS of the rat colon.

Influence of hyperthermia on carotid blood flow using 99mTc-HMPAO

Hyperthermia can be the result of many causes such as environmental conditions, brain tumors and infectious diseases. Since hyperthermia is very common, its role in causing stroke through a decrease in cerebral blood flow needed further emphasis. The aim of this study was to record cerebral blood flow in vitro by using isolated rabbit carotid artery strips and in-vivo using radioactive isotope scanning during temperature elevation. The recording of isometric tension in rabbit carotid artery strips in organ baths, and the scintigraphic cerebral imaging of technetium-99m-hexamethyl-propyleneamineoxime (99mTc-HMPAO) using Gamma camera, were acquired at control and higher body temperature by 4 degrees C. Blood pressure was measured through femoral artery and cerebral blood flow was measured through carotid artery. Elevating temperature by 4 degrees C induced reproducible contraction. During hyperthermia, the carotid artery contraction leads to a decrease in cerebral blood flow although the blood pressure did not decrease. The uptake of 99mTc-HMPAO in the brain was significantly reduced. This decrease in cerebral perfusion is regionally dependent, which is more in the frontal area, the cerebral hemispheres than the cerebellum. The decrease was 36+/-3, 37+/-2, 22+/-2%, respectively. Hyperthermia causes carotid artery contraction leading to decrease in cerebral blood flow, which was confirmed by 99mTc-HMPAO images. The decrease is regionally dependent. Since the blood pressure did not decrease by heating, the reduction in cerebral perfusion is mainly due to carotid contraction. The applied neck cooling may be considered as a promising therapeutic strategy for the hyperthermic patient to avoid brain damage. This can be achieved by external application of an ice-water-perfused neck collar.

Synergistic effects of ethanol and hyperthermia on carotid artery vasoconstriction

Heatstroke is a serious condition and clinical studies indicate that vascular stroke increases with excessive consumption of alcohol (ethanol). It was our objective to test the influence of ethanol on cerebral perfusion at normal and higher temperatures. Recording of isometric tension in rabbit carotid artery strips in organ baths with different concentrations of ethanol at 37 degrees C and during hyperthermia (39-43 degrees C) and scintigraphic cerebral imaging of a radioactive isotope in the control situation and during hyperthermia. Stepwise heating induced reproducible reversible graded contraction, proportional to temperature. At high concentrations (toxic levels), ethanol induced an increase in tension and heating potentiated these responses. Extracellular Mg(2+) potentiated both heat-induced contraction and ethanol-induced contraction while extracellular Ca(2+) had no effect on these responses. During hyperthermia and ethanol scintigraphic isotope uptake was reduced in cortical and cerebellar regions. Carotid artery vasomotor tone is temperature dependent and heating induces vasoconstriction. Alcohol (ethanol) at 37 degrees C elicited carotid artery contraction at high concentrations (toxic levels) but at any concentration during elevated temperature (39-43 degrees C). Ethanol potentiated the effect of hyperthermia-induced vasoconstriction and reduced cerebral perfusion as shown by radionuclide imaging. The synergistic effect of ethanol and hyperthermia may induce heat stroke and brain damage.

Effects of ovariectomy and oestrogen replacement on the function and expression of Rho‐kinase in rat bladder smooth muscle

To investigate the effects of ovariectomy and oestrogen replacement on the function and expression of Rho-kinase in rat bladder smooth muscle, as the actual effects of oestrogen deprivation on bladder smooth muscle are unclear. Female Sprague-Dawley rats were placed into one of three groups: sham-operated, bilateral ovariectomy-only, and bilateral ovariectomy plus oestrogen replacement groups. In the last group, oestrogen was replaced by weekly injection of beta-estradiol 17-cypionate (250 microg/kg subcutaneously for 6 weeks) beginning at 1 week after ovariectomy, whereas the other groups received vehicle-only injections for 6 weeks. After treatment, the bladder was removed for muscle strip studies to evaluate the effects of Y-27632, a specific inhibitor of Rho-kinase, on baseline tension and carbachol-induced tonic contractions. Also, the protein expression of RhoA and Rho-kinase isoenzymes was assessed by Western blot analysis. Of the three groups, incubation with 10 microm Y-27632 resulted in the largest decrease in baseline tension of strips from the bilateral ovariectomy-only group, but this was not statistically significant (P > 0.05). For carbachol-induced tonic contractions, strips from the bilateral ovariectomy-only group were attenuated the most among the three groups after adding Y-27632 (P < 0.05). However, there were no significant differences in the levels of RhoA and the two Rho-kinase isoenzymes in bladder tissues from the three groups. Our data show that oestrogen might inhibit the function of Rho-kinase in bladder smooth muscle, while having no significant effect on its expression. This finding might help to explain the greater incidence of urinary tract symptoms suggestive of overactive bladder after the menopause in women.

Low Temperature Decreased Tension in Isolated Hypertrophic Human Nasal Mucosa

The purpose of this study was to evaluate the effect of low temperature on basal tension in isolated hypertrophic human nasal mucosa with or without alpha1-agonist stimulation. A tissue bath for isolated nasal mucosa was used. Tension in strips of human turbinate mucosa that were untreated and treated with an alpha1-adrenoreceptor agonist, methoxamine (10 microM), was recorded continuously in a stepwise manner in temperatures that varied from 37 to 10 degrees C. The changes of tension in the human nasal mucosa were found to be temperature-dependent in both untreated and treated tissues, with tension decreasing to 48.6% at 10 degrees C in comparison with 100% at 37 degrees C in the untreated group, the presence of methoxamine (10 microM) had minimal effect. Low temperature induced a rapid and reproducible relaxation in isolated hypertrophic human nasal mucosa that was not affected by the presence of the alpha1-agonist methoxamine (10 microM).

Aging-related changes of intracellular Ca 2+ stores and contractile response of intestinal smooth muscle

In this study, we investigated the effect of aging on intracellular Ca 2+ stores, as sarcoendoplasmic reticulum (SR) and mitochondria, and the influence of these compartments on contraction of rat colon smooth muscle [Bitar, K.N., 2003. Aging and neural control of the GI tract V. Aging and gastrointestinal smooth muscle: from signal transduction to contractile proteins. Am. J. Physiol. Gastrointest. Liver. Physiol. 284(1), G1–G7; Marijic, J., Li, Q.X., Song, M., Nishimaru, K., Stefani, E., Toro, L., 2001. Decreased expression of voltage-and Ca 2+-activated K + channels in coronary smooth muscle during aging. Circ. Res. 88, 210–234; Rubio, C., Moreno, A., Briones, A. Ivorra, M.D., D'Ócon, P., Vila, E., 2002. Alterations by age of calcium handling in rat resistance arteries. J. Cardiovasc. Pharmacol. 40(6), 832–840]. Calcium stores and contraction were evaluated by simultaneous measurements of fluorescence and tension in smooth muscle strips loaded with fura-2. Results showed that activation of muscarinic receptors by methylcholine (MCh, 10 μM), induced a greater contraction in aged rats than in adult animals. The inhibition of Ca 2+ ATPase by thapsigargin (TG, 1 μM) did not prevent the refilling of SR either in adult or aged rats. MCh, in the presence of TG, induced an increase in transient fluorescence, indicating a release of Ca 2+ from TG-insensitive compartment. The mitochondrial uncoupler, FCCP (5 μM), caused a greater increase in intracellular Ca 2+ and tension in aged rats, indicating that mitochondria may accumulate more Ca 2+ during aging. The present results show that changes in intracellular Ca 2+ stores, such as mitochondria and SR, affect contraction and may cause dysfunctions during aging that could culminate in severe alterations of Ca 2+ homeostasis and cell damage.

Regional distribution of wall thickness and failure properties of human abdominal aortic aneurysm

The regional distribution of wall thickness and failure properties in human abdominal aortic aneurysm (AAA) was explored. Three unruptured and one ruptured AAA were harvested as a whole during necropsy. Thickness was measured at about every 1.5 cm 2 wall surface area for an average of 100 measurement sites per AAA. Multiple longitudinally oriented rectangular specimen strips were cut at various locations from each AAA for a total of 48 strips. The strips were subjected to uniaxial extension until failure. Wall thickness varied regionally and between AAA from as low as 0.23 mm at a rupture site to 4.26 mm at a calcified site (median=1.48 mm). Wall thickness was slightly lower in the posterior and right regions. The failure tension (ultimate) of specimen strips varied regionally and between AAA from 5.5 N/cm close to a blister site in the ruptured AAA to 42.3 N/cm at the undilated neck of a 4 cm diameter unruptured AAA (median=14.8 N/cm). Failure stress (ultimate) varied from 33.6 to 235.1 N/cm 2 (median=126.6 N/cm 2). There was no perceptible pattern in failure properties along the circumference. Failure tension of specimen strips at or close to blisters was mostly low. The rupture site in the ruptured aneurysm had the lowest recorded wall thickness of 0.23 mm with only slightly higher readings within a 1 cm radius. The failure tension of the specimen strip close to the rupture site was low (11.1 N/cm) compared to its neighborhood in the ruptured aneurysm.

On the modeling and simulation of induced anisotropy in polycrystalline metals with application to springback

The presence of initial, and the development of induced, anisotropic elastic and inelastic material behavior in polycrystalline metals, can be traced back to the influence of texture and dislocation substructural development on this behavior. As it turns out, via homogenization or other means, one can formulate effective models for such structure and its effect on the macroscopic material behavior with the help of the concept of evolving structure tensors. From the constitutive point of view, these quantities determine the material symmetry properties. Most importantly, all dependent constitutive fields (e.g., stress) are by definition isotropic functions of the independent constitutive variables, which include these evolving structure tensors. The evolution of these tensors during loading results in an evolution of the anisotropy of the material. From an algorithmic point of view, the current approach leads to constitutive models which are quite amenable to numerical implementation. To demonstrate the applicability of the resulting constitutive formulation, we apply it to the case of metal plasticity with combined hardening involving both deformation- and permanently induced anisotropy. Comparison of simulation results based on this model for the bending tension of aluminum-alloy sheet-metal strips with corresponding experimental ones show good agreement.

Postjunctional modulation by muscarinic M2 receptors of responses to electrical field stimulation of rat detrusor muscle preparations

1. The aim of the present study was to examine the modulator influence of muscarinic M(2) receptors on responses of rat urinary bladder detrusor muscle evoked by endogenous stimuli, i.e. by stimulation of the bladder innervation. 2. Responses were evoked by electrical field stimulation (EFS; 2-20 Hz, 0.8 ms, 60 V) of isolated strip preparations mounted in organ baths. The tension of the muscle strips was recorded digitally. EFS was performed by applying stimulation with either a short duration (5 s) or a longer duration (to reach peak response; approximately 20 s). 3. Effects of muscarinic receptor antagonists (muscarinic M(1)/M(3) receptor selective: 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP); muscarinic M(2) receptor selective: methoctramine), a beta-adrenergic antagonist (propranolol) and an adenosine receptor antagonist (8-p-sulfophenyltheophylline) were assessed on contractile activity and on poststimulatory relaxations. 4. Low concentrations of methoctramine (10(-8) m) reduced or tended to reduce the EFS-induced contraction, e.g. at 2 Hz by 12% while methoctramine at 10(-7) m had no significant effect. In addition, in the presence of 4-DAMP (10(-9) m), which tended to inhibit contractions at all frequencies (2-20 Hz; -17 to -25%), methoctramine at 10(-8) and 10(-7) m induced a further reduction of the contractile responses (-5 to -10%; 2-20 Hz). 5. The beta-adrenergic receptor antagonist propranolol (10(-6) m) and the adenosine receptor antagonist 8-p-sulfophenyltheophylline (10(-6) m) both increased contractile responses by 9-21% (2-10 Hz, long duration; P < 0.05-0.001) as a consequence of antagonizing relaxatory stimuli. Neither antagonist affected the contractile responses to EFS with the short duration stimulation. Poststimulatory relaxations were reduced by 30-60% (P < 0.05) by propranolol and by 40-60% (P < 0.001) by 8-p-sulfophenyltheophylline, but for 8-p-sulfophenyltheophylline only after stimulation with the short duration. 6. In the presence of methoctramine (10(-7) m), the 8-p-sulfophenyltheophylline-induced increases of the contractile response to long duration EFS were significantly enhanced at 10 Hz (+12 +/- 4%; P < 0.05), whereas no such enhancement of the propranolol inhibitory effect occurred in the presence of methoctramine. However, poststimulatory beta-adrenoceptor-evoked relaxations after short duration EFS were increased by about 35% in the presence of methoctramine, but not those after long duration. 7. Thus, muscarinic M(2) receptor activation inhibits adenosine receptor- and beta-adrenoceptor-evoked relaxations of the rat detrusor muscle. The inhibition occurs via a transient postjunctional mechanism that mainly affects responses with a short latency.

Hyperthermia-induced vasoconstriction of the carotid artery, a possible causative factor of heatstroke.

Clinical and experimental studies indicate that hyperthermia can cause heatstroke with cerebral ischemia and brain damage. However, no study has examined the direct effects of heating carotid artery smooth muscle and tested the hypothesis that hyperthermia induces arterial vasoconstriction and, thereby, decreases cerebral blood flow. We recorded isometric tension of rabbit carotid artery strips in organ baths during stepwise temperature elevation. The heating responses were tested at basal tone, in norepinephrine- and KCl-precontracted vessels, and after electrical field stimulation. Stepwise heating from 37 degrees C to 47 degrees C induced reproducible graded contraction proportional to temperature. The responses could be elicited at basal tone and in precontracted vessels. Heating decreased the contractile responses to norepinephrine and electrical field stimulation but increased contraction to KCl. These responses were not eliminated by pretreatment with the neuronal blocker tetrodotoxin. Our results demonstrate that heating carotid artery preparations above 37 degrees C (normothermia) induced a reversible graded vasoconstriction proportional to temperature. In vivo this reaction may lead to a decrease in cerebral blood flow and cerebral ischemia with brain damage as in heatstroke. The heating-induced contraction is not mediated by a neurogenic process but is due to altered transcellular Ca2+ transport. Cooling, in particular of the neck area, therefore, should be used in the treatment of heatstroke.

IgA sensitizes airway smooth muscle to histamine

Rationale IgA is an important defense against infectious pathogens, which are common triggers of asthma symptoms. We recently reported that primary cell cultures of human airway smooth muscle (ASM) cells express the IgA receptor (pIgR) that binds polymeric IgA (pIgA) but not monomeric IgA (mIgA), and that pIgA increases cytosolic calcium - a necessary prequel to smooth muscle contraction and therefore bronchoconstriction. In this study, we asked if pIgA sensitizes ASM to histamine-induced responses. Methods Cytosolic calcium was measured in Fura2-loaded human ASM cells stimulated first with histamine 10 −6M and then treated for 2h with buffer, pIgA or mIgA. Post-incubation histamine-induced cytosolic calcium concentrations were compared to the pre-incubation response. Tension was measured in isolated canine tracheal ASM strips first in response to histamine 10 −5M and then treated for 4h with buffer, pIgA or mIgA. Post-incubation histamine-induced tension was compared to the pre-incubation response. Results Incubation with pIgA (0.12 μg/ml) significantly augmented the histamine-induced increase in cytosolic calcium in human ASM cells compared to mIgA (12 μg/ml) or buffer (p<0.05). Similarly, incubation with pIgA (6 μg/ml) appreciably enhanced histamine-induced increases in tension (by 2g) in canine tracheal ASM strips compared to mIgA 3 μg/ml (0.36g) or buffer (0.35g; p<0.05). Conclusions Incubation with pIgA sensitizes human ASM cells and canine tracheal ASM strips to histamine. Because IgA is an important epithelial defense against viral and bacterial attachment, functional responses to IgA in ASM may account, at least in part, for the worsening of symptoms during upper respiratory tract infections in patients with allergic asthma.

Locally released norepinephrine in the oxygen-dependent regulation of vascular tone of human umbilical vein.

In a previous study, human umbilical vein preparations constricted at PO(2) values above the physiologic intrauterine PO(2) range and dilated at hypoxia. Denudation of the endothelium reversed the hypoxic vasodilatation only, suggesting the release of a nonendothelial vasoconstrictor. We therefore hypothesized that norepinephrine from adrenergic nerve terminals could be responsible for the observed constricting effects. We measured intracellular membrane potential and isometric tension of human umbilical vein strips with and without functional adrenergic denervation by 6-OH-dopamine during variation of PO(2). With PO(2) increasing from 5 to 104 mm Hg, intact preparations depolarized of from -58.6 +/- 1.1 mV (SEM) to -53.3 +/- 1.0 mV (p < 0.001) and isometric tension increased from 0.673 +/- 0.037 g to 0.825 +/- 0.044 g (p < 0.02). Intact preparations pretreated with 6-OH-dopamine depolarized from -58.0 +/- 0.5 mV to -55.8 +/- 0.6 mV (p < 0.01), and isometric tension increased from 0.598 +/- 0.040 g to 0.661 +/- 0.018 g (p < 0.02). At Po(2) values above the physiologic intrauterine umbilical venous Po(2) range, membrane potential and isometric tension were significantly lower in preparations with 6-OH-dopamine pretreatment compared with matched controls (p < 0.05). Denudation of the endothelium reversed the hypoxic hyperpolarization and vasodilatation observed in intact preparations. However, membrane potential and isometric tension were not different between endothelium-denuded preparations with and without 6-OH-dopamine pretreatment. We conclude that locally released norepinephrine contributes to the depolarization and vasoconstriction of the human umbilical vein at hyperoxia but does not antagonize the endothelium-dependent vasodilation at hypoxia.

Nitric oxide and endothelin in oxygen-dependent regulation of vascular tone of human umbilical vein.

We investigated the possible contribution of nitric oxide (NO) and endothelin (ET) to oxygen-dependent regulation of human umbilical vein vascular tone by simultaneous registration of intracellular membrane potential and isometric tension of vessel strips with and without NO synthase inhibition [10-4 M N omega-nitro-L-arginine methyl ester (L-NAME)], ETA receptor blockade (10(-5) M BQ-123), or ETB receptor blockade (10(-7) M BQ-788) at Po2 values in the bath solution between 5 and 104 mmHg. Increasing PO2 above the physiological intrauterine range resulted in depolarization and an increase of isometric tension, whereas lowering PO2 resulted in hyperpolarization and a decrease in isometric tension. Removal of the endothelium reversed these effects. At PO2 values below 39 mmHg, intact preparations treated with either L-NAME, BQ-788, or BQ-123 were more depolarized than controls. In the case of treatment with L-NAME or BQ-123, this was accompanied by an increase in isometric tension. We conclude that it is NO that mediates the hypoxic hyperpolarization and vasodilatation of the human umbilical vein and that ET, via activation of ETB1 receptors on endothelial cells, contributes to this effect.

Contribution of store-operated Ca 2+ entry to pH o-dependent changes in vascular tone of porcine coronary smooth muscle

Vascular smooth muscle contracts on increases of extracellular pH (pH o) and relaxes on pH o decreases possibly resulting from changes in transsarcolemmal Ca 2+ influx. Therefore, we studied store-operated Ca 2+ entry (SOCE; i.e. capacitative Ca 2+ entry (CCE)) during acidification (pH o=6.5) and alkalinization (pH o=8.0) in isolated porcine coronary smooth muscle cells (SMCs) by monitoring cytoplasmic Ca 2+ ([Ca 2+] i) and divalent cation entry (Mn 2+ quench) with fura-2/AM-fluorometry. Additionally, we evaluated the contribution of SOCE to pH o-dependent changes in isometric tension of porcine coronary smooth muscle strips. SOCE elicited in SMCs by the SERCA inhibitor BHQ was strongly modulated by pH o showing a decrease upon acidification and vice versa an increase upon alkalinization. BHQ-mediated tension of smooth muscle strips also revealed strong pH o dependence. In contrast, L-VOC-dependent tension ([K +] o=20 and 40 mmol l −1) was remarkably less affected by pH o changes. Moreover, refilling of depleted Ca 2+ stores after repeated M 3-cholinergic receptor stimulation could be almost completely inhibited by SKF 96365 and was markedly reduced by acidification and considerably enhanced by alkalinization pointing to a major role of SOCE in refilling. We conclude that vascular tone particularly responds to alterations in pH o whenever SOCE substantially contributes to the amount of activator Ca 2+ for contraction.