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PubMed2005

Relationship between structural remodeling and reactivity in pulmonary resistance arteries from hypertensive piglets.

In neonatal pulmonary hypertension, the pulmonary arteries fail to adapt to extrauterine life and remain thick walled. In a previous study on normal neonatal resistance arteries, perfusion myography and confocal microscopy showed that responses to agonist stimulation were related to wall structure. We hypothesized that in hypertensive resistance pulmonary arteries, an enhanced response to contractile and relaxant agonist stimulation would be associated with an increased wall thickness and abnormal postnatal cytoskeletal remodeling of smooth muscle cells (SMC). Pulmonary arteries (110-140 microm external diameter) from normal piglets and those exposed to chronic hypobaric hypoxia from birth or from 3 d of age were mounted on a perfusion myograph. Lumen diameter and SMC nuclear positions were tracked after addition of KCl, the thromboxane mimetic U46619, and bradykinin. After fixation in situ, SMC dimensions were measured using confocal and electron microscopy. In all hypertensive animals, wall thickness and SMC density were increased and SMC length/width ratio decreased. After hypoxic exposure for 3 d, arteries from animals exposed from birth showed a greater and faster contractile response than controls, but arteries from piglets first exposed at 3 d of age did not, though both showed similar structural appearance. Increase of exposure to 11 d elicited an enhanced response and further cytoskeletal remodeling. All vessels relaxed fully to bradykinin. SMC remodeling and reactivity appear to be influenced by the age at onset and the duration of the hypoxic insult.

Animals↗
PubMed2007

Adrenomedullin-2, a novel calcitonin/calcitonin-gene-related peptide family peptide, relaxes rat mesenteric artery: influence of pregnancy.

Adrenomedullin-2 (ADM2), a novel calcitonin/calcitonin-gene-related peptide family peptide, is reported to reduce blood pressure in both normal and hypertensive rats. This study demonstrates gestational regulation of circulatory ADM2 in rat plasma. ADM2 dose-dependently reduces the mean arterial pressure in rats, whereas the hypotensive effect of ADM2 is significantly higher during pregnancy. In addition, immunoreactive ADM2 protein is distributed in perivascular fibers of rat mesenteric artery, and levels of pre-pro-ADM2 are significantly (P<0.05) elevated in pregnant compared with nonpregnant rat mesenteric artery. Furthermore, incubation of endothelium intact arterial tissue from pregnant rats with ADM217-47, an ADM2 antagonist, shifted the dose-dependent relaxation curve to the right in wire myography. Inhibition of soluble guanylate cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 microM) or endothelial nitric oxide synthase with N-nitro-L-arginine methyl ester (100 microM) reduced the relaxation of mesenteric artery induced by ADM2. Inhibition of adenylate cyclase with SQ22536 (10 microM) or protein kinase A with the Rp diastereomer of cyclic adenosine 3',5'-phosphorothioate (10 microM) also reduced the maximal relaxation responses induced by ADM2. Blockade of calcium-activated potassium channels with tetraethylammonium chloride (1 mM) inhibited the ADM2-induced relaxation, whereas blockade of ATP-sensitive potassium channels with glybenclamide (10 microM) did not affect the relaxation response. Hence the mechanism of ADM2-induced vasorelaxation is nitric oxide and receptor mediated and cGMP and cAMP dependent and occurs through activation of calcium-activated potassium channels. In conclusion, rat pregnancy is associated with increased levels of circulatory and vascular tissue ADM2 with concomitant increase in the in vivo hypotensive effect of ADM2 and vascular reactivity of mesenteric artery to ADM2, thus suggesting involvement of ADM2 in vascular adaptations during pregnancy.

Adrenomedullin↗
PubMed2003

Glucocorticoids and insulin sensitivity: dissociation of insulin's metabolic and vascular actions.

Insulin sensitivity in tissues such as a skeletal muscle and fat is closely correlated with insulin action in the vasculature, but the mechanism underlying this is unclear. We investigated the effect of dexamethasone on insulin-stimulated glucose disposal and vasodilation in healthy males to test the hypothesis that a reduction in glucose disposal would be accompanied by a reduction in insulin action in the vasculature. We performed a double-blind, placebo-controlled, cross-over trial comparing insulin sensitivity (measured by the euglycemic hyperinsulinemic clamp) and vascular insulin action (measured by small vessel wire myography) in young healthy males allocated to placebo or 1 mg dexamethasone twice daily for 6 d, each in random order. Six days of dexamethasone therapy was associated with a 30% (95% confidence interval, 19.1-40.0%) fall in insulin sensitivity. Despite this, there was no difference in insulin-mediated vasodilation between phases. Dexamethasone had no effect on circulating markers of endothelial function, such as D-dimer, von Willebrand factor, and tissue plasminogen activator. By short-term exposure to high dose dexamethasone we were able to differentially affect the metabolic and vascular actions of insulin. This implies that, using this model, there is physiological uncoupling of the effects of insulin in different tissues.

Acetylcholine↗
PubMed2005

Small artery endothelial dysfunction in postmenopausal women: in vitro function, morphology, and modification by estrogen and selective estrogen receptor modulators.

OBJECTIVE: Our objective was to assess vascular endothelial function and morphology in resistance vasculature from healthy pre- and postmenopausal women in vitro and to determine potential mechanisms of vascular protection by estrogenic compounds. METHODS: Arteries (approximately 220 microm) were dissected from sc fat biopsies obtained from healthy premenopausal and postmenopausal women. Flow-mediated dilatation, agonist-induced endothelium-dependent and -independent relaxation, and myogenic responses to changes in intraluminal pressure were evaluated before and after incubation (3 h) with 17beta-estradiol, propyl pyrazole triol [a selective estrogen receptor-alpha (ERalpha) agonist], raloxifene (a second-generation selective ER modulator), and the phytoestrogen genistein, using pressure myography technique. In addition, endothelial morphology was assessed in arteries from pre- and postmenopausal women, and distribution of ERs within the artery wall from postmenopausal women was evaluated. RESULTS: Functional and morphological disturbances of endothelial function were observed in small arteries from postmenopausal women. Incubation with 17beta-estradiol improved postmenopausal resistance artery function, an effect mimicked by propyl pyrazole triol but not raloxifene or genistein. Immunohistochemical staining revealed similar expression of ERalpha and ERbeta in the smooth muscle of arteries from postmenopausal women; however, ERalpha was dominant in endothelium. CONCLUSIONS: The resistance arteries from postmenopausal women show functional and morphological abnormalities. ERalpha may contribute to vascular protection by estrogens in the peripheral resistance circulation in postmenopausal women. Selective ERalpha agonists warrant further investigation as therapeutic agents for prevention of cardiovascular disease in postmenopausal women.

Adult↗
PubMed2002

Altered vascular function in young women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by hyperinsulinemic insulin resistance, a metabolic disorder that in other circumstances is associated with increased cardiovascular risk. We compared macrovascular and microvascular function in 19 women with PCOS with 12 control subjects matched as a group for body mass index. Macrovascular function was assessed by recording pulse wave velocity (PWV) across the aorta and brachial artery. Microvascular function was studied by wire myography, by measuring the concentration response curve to norepinephrine (NE) before and after incubation with insulin (100 and 1,000 pM). PWV at the level of the brachial artery was found to be significantly elevated in the PCOS group [9.08 (range, 8.34-11.15) m/sec(-1) vs. 8.27 (range, 7.5-9.01) m/sec(-1); P = 0.03]. In contrast, PWV measured in the aorta did not differ between the two groups [7.49 +/- 1.21 vs. 7.84 +/- 1.44 m/sec(-1); P = 0.8]. In vessels from control subjects, insulin reduced the contraction response to NE. At an insulin concentration of 100 pM, NE negative log EC50 (pD(2)) was 6.2 +/- 0.24 vs. 6.7 +/- 0.15 (P = 0.02). At a concentration of 1,000 pM, NE pD(2) was 6.4 +/- 0.14 vs. 6.9 +/- 0.19 (P = 0.0006). Both concentrations also caused attenuation in maximal tension developed in response to NE (insulin 100 pM, 12 +/- 3%, P = 0.002; insulin 1,000 pM, 17 +/- 5%, P = 0.009). In contrast, there was no change in the PCOS group with insulin at 100 pM for either pD(2) (6.7 +/- 0.24 vs. 6.8 +/- 0.27; P = 0.3) or maximum contraction (-0.4 +/- 2%; P = 0.8). At 1,000 pM, there was a change in pD(2) (6.4 +/- 0.2 vs. 6.8 +/- 0.2; P = 0.003) but not maximum contraction (4 +/- 3%; P = 0.2). In conclusion, this study is the first to demonstrate increased vascular stiffness and a functional defect in the vascular action of insulin ex vivo in patients with PCOS. We suggest that these findings are indicative of insulin resistance at a vascular level in women without overt cardiovascular disease.

Acetylcholine↗
PubMedDate not supplied

From larynx to vocal ability. New electro-physiological data.

The objectives of phoniatric diagnostics and therapy are the small muscles of the voice- and speech-producing organs. Electrodiagnostics of functional and neuromuscular disorders in this field are difficult, because of the hidden anatomical situation. On the other hand electrodiagnostics enable an objective diagnosis and documentation. The method offers the possibility of electromyography of the larynx, palate and tongue during voluntary muscle contraction and neuromyography after electrostimulation of the afferent nerve, especially the X cranial nerve and reflex myography after electrostimulation of the contralateral nerve. The theory on which the method is based is described for both healthy and diseased neuromuscular units. The convenience of application of the electrodes during zoom endoscopy under surface anesthesia in the alert patient is shown, with special emphasis on 80 micron copper wire electrodes, especially in disorders of coordination. Apart from being well tolerated by the patients, the method enables a clear differentiation of organic lesions, i.e. into degenerative and non-degenerative paralysis. In addition to this, electromyogram reflex measurements can verify psychogenic aphonia or other functional dysfunctions. Myopathies and neurological diseases that cause voice and speech disorders can be diagnosed using electrodiagnostics. At present the main field for this method undoubtedly is the differential diagnosis of palsies; but due to its objective measurement and quantitation of disorders of coordination it should also be used in the diagnosis of speech and voice disorders of different etiologies. Computerized electromyography analysis and electro-stimulation with train should enable an even more detailed analysis in the future.

Electrodiagnosis↗
PubMed1992

Testing otolith function.

Otolithic signals contribute to; (1) perception of orientation and linear motion, (2) generate compensatory eye movements in response to linear acceleration of the head and (3) participate in the co-ordination of movement and balance. Tests of these functions shown to be useful in identifying clinical disorders have been reviewed: (1) Evaluation of orientation to gravity, as estimated by adjustment of the visual vertical, indicates deranged otolith function at a peripheral or central level and the sensitivity of this test can be enhanced by performing estimates during centrifugation on a motorised turntable. Estimation of thresholds of self motion on a parallel swing identifies global reduction or unilateral loss of peripheral function, with central disorders awaiting study. (2) Otolith ocular reflexes to linear head translation can be used to demonstrate overall integrity of peripheral function and reveal central abnormalities. Counter-rolling responses to head roll-tilt and measurements of cyclodeviation of the eyes demonstrate functional asymmetries, with some lateralising value, particularly in central lesions. Global function and asymmetries may also be evaluated by 'head eccentric' rotational testing, which adds a tangential linear acceleration to the angular stimulus. The linear acceleration enhances the canal response by adding an otolith component. (3) Latency and amplitude of surface electro-myography (EMG) responses in the limbs to sudden falls, which can be recorded with the subject suspended on a hinged bed, indicate gross peripheral abnormality of function and can lateralize disorders of CNS motor pathways. It is concluded that some tests of otolith function can be of use in indicating global loss of peripheral otolith function, others are capable of lateralizing a marked loss of function and all have the potential to give information about central disorders. They all have to be interpreted within the clinical context and, unfortunately, none have yet been shown to be sensitive to partial, particularly unilateral, dysfunction.

Adult↗
PubMed2004

Effects of low-dose continuous combined HRT on vascular function in women with type 2 diabetes.

BACKGROUND: Improvement in vascular endothelial function is widley cited as a beneficial effect of hormone replacement therapy (HRT). Women with type 2 diabetes (T2DM) are at increased cardiovascular risk and have impaired endothelial function. Any benefits of HRT on endothelial function in this group are of particular interest. OBJECTIVES: We assessed effects on vascular function of oral 17beta oestradiol (1 mg) and norethisterone (0.5 mg) in postmenopausal women with T2DM. DESIGN: Double-blind, randomised, placebo-controlled trial. ASSESSMENTS: Twenty-eight women had pulse wave velocity (PWV) and adhesion molecules VCAM-1 and ICAM-1 assessed before and after three months' treatment. Twenty-four women also had gluteal fat biopsy for assessment of resistance vessel function (using wire myography). RESULTS: HRT did not affect PWV, VCAM-1, ICAM-1 or carbachol response. Effects of L-NAME and indomethacin on carbachol sensitivity were similar in both groups. CONCLUSIONS: This HRT preparation had no detectable effect on these measures of endothelial function in women with T2DM.

Arteries↗
PubMed1993

Actions of potassium channel openers in rat detrusor urinae.

This study was performed to investigate the action of potassium channel openers on the mechanical activity of detrusor muscle isolated from rats. Detrusor muscle strips, 15 mm in length, were myographied isometrically in an isolated organ bath. P 1060, RP 49356 and BRL 38277, potassium channel activators, reduced the basal tone and diminished the phasic activity of detrusor concentration-dependently. P 1060, RP 49356 and BRL 38227 suppressed the maximal responses to bethanechol and shifted the concentration-response curves of bethanechol-induced contraction to the right. RP 49356 and BRL 38227 reduced the contraction by low (20 mM) concentration of potassium. P 1060, however, diminished the high (80 mM) and low (20 mM) concentration of potassium-induced contraction. Glibenclamide, an inhibitor of ATP-dependent potassium channel, antagonized the suppressive action of P 1060, RP 49356 and BRL 38227 on the basal tone. Apamin or procaine did not antagonize it significantly. Based on these results, it is suggested that the relaxation of detrusor muscle strip caused by P 1060, RP 49356 and BRL 38227 may predominantly involve opening of the same potassium channel, i.e., the ATP-dependent potassium channel.

Animals↗
PubMed1978

[EMG-findings and nerve conduction velocity in herpes zoster disease (author's transl)].

We have performed a myography on three patients and an additional study of the nerve conduction velocity (CV) on two adult patients suffering from herpes zoster. It could be demonstrated that the affected muscles can suffer at the same time a neuropathy as well as a myopathy. We found fibrillations and CV-reduction also in clinically healthy nerves and muscles. The abnormal findings were most prominent in the clinically affected segments and often suggested an in portio lesion of the motor unit. The infiltration of the spinal ganglion appears to have no paramount significance for the understanding of this disease.

Action Potentials↗
PubMed1999

[Influence of prostatilen on smooth muscle organs functional activity in surgical patients (clinical and experimental study)].

The action of prostatilen on contractile activity of smooth muscles of isolated line slices of urine bladder of Wistar rats (myography) and arterial vessels of cat kidneys (resistography) was studied. On the basis of clinical cases effectiveness of prostatilen was analysed as a treatment restorting urine bladder function in acute reflex urinary retention after operations in the area of rectal sphincter, as well as in treatment of patients with chronic prostatitis. It is shown, that prostatilen produces contractile action on smooth muscles of renal blood vessels in cats and urine bladder walls in rats and it raises contractile activity of smooth muscles of human urine bladder. The results of experimental and clinical investigations make it possible to recommend the application of this bioregulating preparation for treatment and prophylaxis of disturbances in urination.

Adjuvants, Immunologic↗
PubMed1999

A role for N-arachidonylethanolamine (anandamide) as the mediator of sensory nerve-dependent Ca2+-induced relaxation.

We tested the hypothesis that an endogenous cannabinoid (CB) receptor agonist, such as N-arachidonylethanolamine (anandamide), is the transmitter that mediates perivascular sensory nerve-dependent Ca2+-induced relaxation. Rat mesenteric branch arteries were studied using wire myography; relaxation was determined after inducing contraction with norepinephrine. Cumulative addition of Ca2+ caused dose-dependent relaxation (ED50 = 2.2 +/- 0.09 mM). The relaxation was inhibited by 10 mM TEA and 100 nM iberiotoxin, a blocker of large conductance Ca2+-activated K+ channels, but not by 5 microM glibenclamide, 1 mM 4-aminopyridine, or 30 nM apamin. Ca2+-induced relaxation was also blocked by the selective CB receptor antagonist SR141716A and was enhanced by pretreatment with 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (pefabloc; 30 microM), an inhibitor of anandamide metabolism. Anandamide also caused dose-dependent relaxation (ED50 =.72 +/- 0.3 microM). The relaxation was not inhibited by endothelial denudation, 10 microM indomethacin, or 1 microM miconazole, but was blocked by 3 microM SR141716A, 10 mM TEA, precontraction with 100 mM K+, and 100 nM iberiotoxin, and was enhanced by treatment with 30 microM pefabloc. Mesenteric branch arteries were 200-fold more sensitive to the relaxing action of anandamide than arachidonic acid (ED50 = 160 +/- 7 microM). These data show that: 1) Ca2+ and anandamide cause hyperpolarization-mediated relaxation of mesenteric branch arteries, which is dependent on an iberiotoxin-sensitive Ca2+-activated K+ channel, 2) relaxation induced by both Ca2+ and anandamide is inhibited by CB receptor blockade, and 3) relaxation induced by anandamide is not dependent on its breakdown to arachidonic acid and subsequent metabolism. These findings support the hypothesis that anandamide, or a similar cannabinoid receptor agonist, mediates nerve-dependent Ca2+-induced relaxation in the rat.

Animals↗
PubMed1999

[Electromyography in the diagnosis of vibration diseases].

A total of 50 vibration disease patients were assessed by stimulation and needle myography. The authors revealed highly diagnostic parameters: wider range of excitation velocity in motor axons of mixed nerves, preferential decrease in minimal motor velocity, lower number of motor units (MU) functioning, denervation changes of MU action potentials, potentials of spontaneous activity of muscular fibers and fasciculations. Distal muscles of limbs demonstrate the most striking changes in electric activity of MU.

Adult↗
PubMedDate not supplied

[Werdnig-Hoffmann disease. The first prenatal diagnosis in Cuba].

INTRODUCTION: Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by the degeneration of cells of the spinal cord. The gene was localized on chromosome 5q13 and exists in two almost identical forms, which are distinguished by the change of base on exones 7 and 8. Mutations of the gene of survival motoreneuron (SMN) are the cause of illness. CLINICAL CASE: We report, for the first time in Cuba, the prenatal diagnosis of a type II SMA carrier, using molecular methods for direct detection of the mutation on exones 7 and 8 of the SMN gene, and haplo-identification with microsatellite markers of chromosome 5q as an indirect method. A sample of amniotic liquid was taken at 18 weeks of gestation and the DNA extracted. No deletions were detected on exones 7 and 8 of the foetal DNA, which was therefore normal. CONCLUSIONS: Detection of deletions on the SMN gene is a method which permits detection of the condition (healthy or unhealthy) of the foetus, quickly and reliably, without requiring investigation of the entire family to obtain a result. The method does not require radio-active PCR, the results are clear and precise and may be obtained within 24 hours. It may also take the place of invasive methods such as muscle biopsy and electro-myography and contribute to genetic assessment in families in which there is no DNA of the affected child.

Chromosomes, Human, Pair 5↗
PubMed2000

[Immunocorrective treatment in mandibular fractures in inhabitants of the European North].

Consolidation of mandibular fragments in 120 patients with fractures of different location was evaluated by clinical, x-ray, and functional methods (rheography and myography). After conventional treatment the fragments consolidated in 34.5 +/- 0.6 days in unilateral fractures and in 39.3 +/- 0.7 days in bilateral fractures. After combined therapy including immuno-correcting and vasodilating agents recovery was attained 4-5 days earlier.

Adjuvants, Immunologic↗
PubMed2000

New relationship between electrical characteristics of evoked contractions in skeletal muscles during necrobiosis.

Evoked muscle contractions at different stages of necrobiosis were investigated by stimulating impedance myography in patients with vascular pathology and acute or chronic ischemic syndrome of the lower extremities. The threshold and maximum amplitudes and current strength for contraction responses were determined, and the dependence of evoked contractions on stimulating current was evaluated. Approximation of the obtained curves with the well-known force-time excitation curves demonstrated the relationship between excitability and contractility parameters depending on the stage of ischemic necrobiosis. This regularity is a more universal interrelation between muscle electrical characteristics. Electrical characteristics of evoked contractions depend on various factors influencing muscle structure and function.

Arteriosclerosis↗
PubMed2001

Inhibition of Ca2+-induced relaxation by oxidized tungsten wires and paratungstate.

Recent studies of rat mesenteric arteries using a wire myograph detected decreased Ca2+ and acetylcholine-induced relaxation responses. Preliminary experiments indicated the reduced responses were associated with the tungsten wire used in the myograph system. Compared with earlier observations, arteries mounted on aged 28-microm tungsten wire showed decreased maximal Ca2+-induced relaxation responses of arteries precontracted with phenylephrine (91.9 +/- 1.5 versus 54.8 +/- 4.5%, p < 0.001) and reduced sensitivity to Ca2+ (ED50 = 1.65 +/- 0.07 versus 4.58 +/- 0.16 mM, p < 0.001). Similar shifts were seen for acetylcholine. When the surface of the wire was cleaned by abrasion with fine sandpaper, both the ED50 for Ca2+ and maximal relaxation significantly improved. An enhanced sensitivity to Ca2+ was also seen when arteries were mounted on newly purchased 14-microm tungsten or 14-microm 24K gold wire with the rank order: 14-microm gold > 14-microm tungsten >> 28-microm aged tungsten wire. Laser Raman spectral analysis of the aged 28-microm tungsten wire showed that the surface was in an oxidized state that shared spectral characteristics with the paratungstate [W12O42](-12) anion. The effect of the paratungstate anion on arterial relaxation was therefore tested. Paratungstate, but not the structurally dissimilar tungstate and metatungstate anions, significantly reduced the sensitivity and magnitude of relaxation induced by Ca2+ and to a lesser extent, relaxation induced by acetylcholine. To learn whether paratungstate inhibits relaxation through the generation of oxygen radicals, the effect of the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (1 mM) was assessed and found to have no effect. Since Ca2+-induced relaxation is inhibited by iberiotoxin, the effect of paratungstate on K+ channel activity was assessed. Paratungstate had no effect on currents through large conductance, Ca2+-activated K+ channels in whole-cell recordings from vascular smooth muscle cells, ruling out an action at the BK(Ca) channel. We conclude that: 1) surface oxidation of tungsten wire commonly used in wire myography significantly and adversely affects vascular responses to vasodilator compounds, 2) the effect is likely mediated by the paratungstate anion, and 3) the effects of the anion are not associated with free radical generation or K+ channel inhibition.

Acetylcholine↗
PubMed2002

Low-protein diet impairs vascular relaxation in virgin and pregnant rats.

Pregnancy is associated with increases in maternal cardiac output and plasma volume and a reduction in peripheral vascular resistance. Cardiac output and plasma volume are substantially reduced in pregnant rats fed a low-protein diet, but it is not known whether vascular function is also compromised. We have investigated vascular function in virgin and pregnant Wistar rats subjected to dietary protein restriction [9% (w/v) casein, compared with 18% (w/v) casein for controls]. The diets were fed to the groups for 18 days; in the pregnant rats, the diets were given from day 1 of pregnancy. Branches of the mesenteric arteries were studied on day 18 of the dietary period using myography. Significant reductions in sensitivity to acetylcholine occurred in vessels from virgin (P=0.04) and pregnant (P=0.01) rats that had consumed the 9% casein diet. In arteries from the virgin rats on the restricted diet there was also a significant reduction in sensitivity (P=0.0003) and maximum relaxation (P=0.009) to the NO donor spermine NONOate. Mean placental and fetal weights were significantly lower in the rats fed on 9% casein (P<0.0001 and P=0.005 respectively). Thus low-protein diets impair vasodilator responses in female rats. These effects may contribute to the poor cardiovascular adaptation to pregnancy and lower fetal weights associated with restricted protein intake.

Acetylcholine↗