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Biomedical subjects

I Marshall

Publications and source records attributed to I Marshall.

At least 73 records · Page 4Linked to original sources

The role of diacylglycerol and activation of protein kinase C in alpha 1A-adrenoceptor-mediated contraction to noradrenaline of rat isolated epididymal vas deferens.

1. The mechanism of contraction to noradrenaline (pEC50 5.6 +/- 0.1) in the rat epididymal vas deferens (mediated via alpha 1A-adrenoceptors) has been studied in functional experiments. 2. Contractions to noradrenaline at 10(-6) M were potentiated by the diacylglycerol (DAG) kinase inhibitor R 59022 (3 x 10(-7) M) from 49 +/- 4% to 63 +/- 3% maximum response and the time taken from initiation of contraction to the maximum response was reduced from 16 +/- 2 s to 9 +/- 1 s. The same contractions were not significantly potentiated by the DAG lipase inhibitor, U-57,908, 10(-5) M (51 +/- 2% control and 53 +/- 4% in the presence of U-57,908) nor was the time taken from initiation of contraction to the maximum response significantly altered (17 +/- 1 s control and 16 +/- 1 s in the presence of U-57,908). 3. Concentration-dependent contractions to noradrenaline (NA) were reduced by staurosporine (10(-7) M) and the selective protein kinase C inhibitor, calphostin C (10(-6) M) from 68 +/- 2% (NA, 3 x 10(-6) M) to 28 +/- 2% and 20 +/- 2% respectively and from 94 +/- 2% (NA, 3 x 10(-5) M) to 50 +/- 2% and 44 +/- 2% respectively. Contractions to K+ (40 +/- 2% maximum response to NA) were also significantly reduced by staurosporine (10(-7) M) (35 +/- 2%) but not by calphostin C (43 +/- 3%). 4. The phorbol ester, phorbol-12,13-dibutyrate (PDBu), produced a phasic, concentration-dependent contraction (10(-7) M - 10(-4) M) which was 41 +/- 2% of the maximum response to NA at 10(-4) M PDBu. The contraction to PDBu (10(-5) M) was reduced by calphostin C (10(-6) M) from 33 +/- 5% to 4 +/- 1% maximum response to NA. 5. Non-cumulative contractions to NA (10(-8) M - 10(-4) M) were abolished in Ca(2+)-free Krebs solution containing EGTA (1 mM) and were reduced in the presence of nifedipine (10(-6)M) in normal Krebs solution by 91 +/- 2% at 10(-4)M NA. The contraction to PDBu (10(-5)M, 33 +/- 5% maximum response to NA) was also abolished in Ca(2+)-free Krebs solution containing EGTA (1 mM) or by the presence of nifedipine (10(-6)M) in normal Krebs solution. 6. When NA (10(-4)M) was added to vasa deferentia in Ca(2+)-free Krebs solution containing EGTA (1 mM), following its wash out (and with EGTA later removed from the Krebs solution), readdition of Ca2+ (2.5 mM) to the Krebs solution produced no response. Cyclopiazonic acid (10(-5)M), which can deplete Ca2+ from intracellular stores, also produced no contraction. Therefore influx of extracellular Ca2+ is not a consequence of depletion of intracellular Ca2+ stores (capacitative Ca2+ influx). 7. Pre-incubation of tissues for 30 min with either cyclopiazonic acid (10(-5)M) or ryanodine (10(-4)M), which can both deplete intracellular Ca2+ stores, did not reduce the contractions to NA (3 x 10(-6)M). Pre-incubation of vasa deferentia with cyclopiazonic acid (1 or 3 min, when any rise in [Ca2+]i produced by cyclopiazonic acid might still exist) did not potentiate the contraction to PDBu (10(-5)M). Thus mobilization of intracellular Ca2+ may not be required for the activation of protein kinase C involved in these contractions. 8. In conclusion, the contraction of the rat epididymal vas deferens to NA mediated by alpha 1A-adrenoceptors appears to depend upon activation of protein kinase C by diacylglycerol, resulting in the influx of extracellular Ca2+ through voltage-gated Ca2+ channels. There was no evidence for a role of inositol trisphosphate in the contraction to noradrenaline in this tissue.

Animals↗

Different subtypes of alpha 1A-adrenoceptor mediating contraction of rat epididymal vas deferens, rat hepatic portal vein and human prostate distinguished by the antagonist RS 17053.

1. The alpha 1-adrenoceptor subtype mediating contraction of the rat hepatic portal vein to phenylephrine was characterized by use of competitive antagonists previously shown to have selectivity between the expressed alpha 1-subtype clones. Prazosin competitively antagonized the phenylephrine contractions with a pA2 value of 9.2, as did WB 4101 (pA2 9.4), 5-methyl urapidil (pA2 8.6), indoramin (pA2 8.4) and BMY 7378 (pA2 6.5). 2. The pA2 values on the rat portal vein correlated highly with their previously published pA2 values for the alpha 1A-adrenoceptors mediating contraction of the rat epididymal vas deferens and human prostate and poorly with those for the alpha 1B- and alpha 1D-adrenoceptors mediating contraction of the rat spleen and aorta, respectively. The antagonist pA2 values on the rat portal vein correlated highly with their previously published pK1 values for the expressed alpha 1a-clone and poorly with those for the expressed alpha 1b- and alpha 1d-clones. Therefore the results show that contraction of the rat portal vein to phenylephrine is mediated by alpha 1A-adrenoceptors. 3. The novel alpha 1-adrenoceptor antagonist RS 17053 had a relatively high affinity for the alpha 1A-adrenoceptors mediating contraction of the rat epididymal vas deferens (pA2 9.5) compared with the alpha 1B-adrenoceptors in the rat spleen (pA2 7.2) or the alpha 1D-adrenoceptors in the rat aorta (pKB 7.1), in agreement with its selectivity for the expressed alpha 1a-clone. However, RS 17053 had over 100 fold lower affinity for the alpha 1A-adrenoceptors mediating contraction of the rat portal vein (pKB 7.1) and human prostate (pKB 7.1) compared with its affinity for the alpha 1A-adrenoceptors in the rat epididymal vas deferens or the expressed alpha 1a-clone. 4. The difference in affinity of RS 17053 between the rat epididymal vas deferens and rat portal vein cannot be explained by a species difference in the receptor. Therefore RS 17053 may distinguish between subtypes of the alpha 1A-adrenoceptor in the rat portal vein and human prostate compared with those in the rat epididymal vas deferens or the expressed alpha 1a-clone.

Adrenergic alpha-1 Receptor Agonists↗

Effect of insect-growth-disrupting amines and amides on Schistosoma mansoni in vitro.

A series of nonsteroidal alkylamines and alkylamides, which apparently inhibit phytosterol dealkylation in insects and free-living nematodes, as well as steps in the ecdysteroid biosynthetic pathway of insects, are also known to affect growth and development of animal-parasitic nematodes. The effect of these compounds on the motility, pairing, and viability of the trematode, Schistosoma mansoni, maintained in vitro was examined by incorporating the potential inhibitors into the medium employed for parasite culture. The alkylamines were more active than their amide counterparts, killing all parasites within 18 hr when tested at 25 parts per million. At lower concentrations, reductions in schistosome pairing and motility were observed. The functional group of the amine compounds influenced the schistosomicidal activity, with N-ethylamines being more effective than N,N-dimethylamines of identical carbon chain-length. Of all the compounds tested, N-ethyldodecanamine appeared to be the most promising schistosomicidal agent, killing all parasites within 22 hr at 10 parts per million and preventing parasite pairing at 3 parts per million.

Amides↗

Stress and vulnerability in medical students.

One hundred and forty Hong Kong Chinese students were surveyed early in the second year of their medical education (year 2), and compared with 138 students surveyed prior to beginning their first year of medical school and with 74 non-medical university students in their second year. In year 2 students, distress as reflected in their scores on anxiety and depression self-report scales was high, and these students reported greater utilization of health professional services as compared with the other two groups. In year 2 students, concerns related to the medical school environment and curriculum, and whether one has the endurance and ability to be successful were significant correlates with depression and anxiety. Loss of opportunity to maintain social and recreational sources of gratification correlated with anxiety. There was no difference between the sexes with regard to the development of anxiety and depression symptoms. Academically less successful students reported somewhat higher levels of depressive ideation and symptomatology. Trait anxiety correlated with the development of distress, while optimism protected against the development of distress. Active coping styles and positive reinterpretation as a coping strategy correlated negatively with distress, while wishful thinking correlated positively with distress. These findings emphasize the need for greater attention to the psychological well-being of doctors-in-training, in Hong Kong as in the Western world. These findings should be further explored in longitudinal studies, and may be helpful in designing intervention and support programmes for vulnerable students.

Adult↗

Noradrenaline contractions of human prostate mediated by alpha 1A-(alpha 1c-) adrenoceptor subtype.

1. The subtype of alpha 1-adrenoceptor mediating contractions of human prostate to noradrenaline was characterized by use of a range of competitive and non-competitive antagonists. 2. Contractions of the prostate to either noradrenaline (pD2 5.5), phenylephrine (pD2 5.1) or methoxamine (pD2 4.4) were unaltered by the presence of neuronal and extraneuronal uptake blockers. Noradrenaline was about 3 and 10 times more potent than phenylephrine and methoxamine respectively. Phenylephrine and methoxamine were partial agonists. 3. Pretreatment with the alkylating agent, chlorethylclonidine (10(-4M) shifted the noradrenaline concentration-contraction curve about 3 fold to the right and depressed the maximum response by 31%. This shift is 100 fold less than that previously shown to be produced by chlorethylclonidine under the same conditions on alpha 1B-adrenoceptor-mediated contractions. 4. Cumulative concentration-contraction curves for noradrenaline were competitively antagonized by WB 4101 (pA2 9.0), 5-methyl-urapidil (pA2 8.6), phentolamine (pA2 7.6), benoxathian (pA2 8.5), spiperone (pA2 7.3), indoramin (pA2 8.2) and BMY 7378 (pA2 6.6). These values correlated best with published pKi values for their displacement of [3H]-prazosin binding on membranes expressing cloned alpha 1c-adrenoceptors and poorly with values from cloned alpha 1b- and alpha 1d-adrenoceptors. 5. The good correlation between the functional data on the prostate and the binding data on the expressed alpha 1c-subtype clone for the affinities of the competitive antagonists suggests that they are the same subtype. As the expressed alpha 1c-adrenoceptor clone corresponds to the alpha 1A-adrenoceptor expressed in tissues, contraction of the human prostate to noradrenaline is therefore mediated by an alpha 1A-adrenoceptor.

Adrenergic alpha-1 Receptor Agonists↗

The role of capacitative Ca2+ influx in the alpha 1B-adrenoceptor-mediated contraction to phenylephrine of the rat spleen.

1. The mechanism of contraction to phenylephrine in the rat spleen (mediated via alpha 1B-adrenoceptors) has been studied in functional experiments. 2. The concentration-dependent contraction of the rat spleen to cumulative additions of phenylephrine (pD2 4.8 +/- 0.1) was not significantly reduced by the selective protein kinase C (PKC) inhibitor, calphostin C (10(-6)M) or potentiated by the DAG kinase inhibitor, R59022 (10(-6) M). 3. Contraction of the rat spleen in normal Krebs solution containing Ca2+ (2.5 mM) to a single concentration of phenylephrine (3 x 10(-4) M) produced a maximal response consisting of an initial phasic component and a more slowly developing tonic component. However in Ca(2+)-free Krebs solution (containing EGTA), phenylephrine (3 x 10(-4)M) produced only a phasic contraction which was reduced to 46 +/- 3% maximum response to phenylephrine in normal Krebs solution. 4. In some tissues after the contraction to phenylephrine (3 x 10(-4) M) in Ca(2+)-free Krebs solution (containing EGTA), the phenylephrine was washed out and the tissue was allowed to recover. After 2 h, upon addition of Ca2+ (2.5 mM) to the Krebs solution (EGTA now removed) a tonic contraction developed in the tissue (97 +/- 4% maximum response to phenylephrine). 5. Cyclopiazonic acid produced a tonic contraction of the rat spleen with a maximum effect at 10(-5) M (202 +/- 8% maximum response compared with that to phenylephrine). The contraction to CPA (10(-5) M) was reduced in Ca(2+)-free Krebs solution containing EGTA (30 +/- 4% of the maximum response to phenylephrine). One hour after the end of the contraction in Ca(2+)-free Krebs solution (EGTA now removed), upon addition of Ca2+ (2.5 mM) to the Krebs solution a tonic contraction developed in the tissue (263 +/- 12% maximum response to phenylephrine). 6 In Ca2+-free Krebs solution, after the spleen had been incubated with cyclopiazonic acid for 30 min,the subsequent contraction to phenylephrine (3 x 10-4 M) was reduced from 46+/-3% to 9+/-2%maximum response to phenylephrine.7 Cumulative contractions to phenylephrine and the contraction to cyclopiazonic acid (10-5 M) in the spleen were not significantly affected by nifedipine (10-6 M). The non-selective Ca2+channel blocker,SK&F 96365 (3 x 10-5 M) reduced the maximum response for the cumulative additions of phenylephrine to 35+/-1% and the contraction to CPA (10-5 M) from 202+/-8% to 108+/-8% maximum response to phenylephrine.8 The tyrosine kinase inhibitors genistein (3 x 10-5 M and tyrphostin 23 (10-4 M), reduced the maximum response to phenylephrine in the spleen to 51+/-4% and 44+/-5% respectively and the maximum contraction to cyclopiazonic acid (3 x 10-6 M) in the spleen from 132 +/- 6% to 82 +/-5% and 80 +/- 7% maximum response to phenylephrine respectively without affecting contractions to K+.9 In conclusion, these results are consistent with the contraction of the rat spleen to phenylephrine consisting of an initial phasic contraction due to release of intracellular Ca2+ and a larger tonic contraction due to capacitative Ca2+ influx through non-voltage-gated Ca2+ channels and which may involve a tyrosine kinase. This suggests that inositol triphosphate but not diacylglycerol is involved in the contraction.

Adrenergic alpha-1 Receptor Agonists↗

Evidence for a functional alpha 1A- (alpha 1C-) adrenoceptor mediating contraction of the rat epididymal vas deferens and an alpha 1B-adrenoceptor mediating contraction of the rat spleen.

1. The alpha 1-adrenoceptor subtype mediating contraction of the rat epididymal vas deferens and rat spleen has been investigated by use of alpha 1-adrenoceptor antagonists that have shown selectivity between the different cloned receptor subtypes. 2. In the rat epididymal vas deferens the potency of noradrenaline and phenylephrine was increased in the presence of neuronal and extra-neuronal uptake blockers, cocaine and beta-oestradiol, but these did not alter that of methoxamine. The order of potency of the agonists in the presence or absence of uptake blockade was noradrenaline > phenylephrine > methoxamine. In the rat spleen the potency of these agonists was not altered in the presence of cocaine and beta-oestradiol, and their order of potency was the same as in the vas deferens. 3. The non subtype selective alpha 1-adrenoceptor antagonist prazosin (up to 1 x 10(-7) M) was found to antagonize contractions to noradrenaline in the vas deferens competitively (pA2 9.2), but only in a non competitive manner in the spleen. Contractions to phenylephrine in the spleen however were competitively antagonized by prazosin (up to 1 x 10(-7) M) with a pA2 of 9.2. This suggests that there is an alpha 1- and a non alpha 1-adrenoceptor response to noradrenaline in the rat spleen. 4. Pretreatment with chlorethylclonidine (10(-4) M for 30 min) did not alter the noradrenaline contractions in the vas deferens, but contractions to noradrenaline and phenylephrine in the spleen were shifted 30 and 300 fold to the right of the control curve, respectively. This suggests that only the contractions in the spleen were mediated by alpha 1B-adrenoceptors. 5. The noradrenaline contractions in the vas deferens were competitively antagonized by WB 4101 (pA29.6), 5-methyl-urapidil (pA2 8.7), phentolamine (pA2 8.3), benoxathian (pA2 9.4), spiperone (pA2 7.5),indoramin (pA2 8.4) and BMY 7378 (pA2 6.7), consistent with the affinities of these antagonists in binding studies on tissue alpha 1A-adrenoceptors. These values correlated best with their published affinities on the expressed alpha 1c-adrenoceptor clone and poorly with those at either the expressed alpha lb- or alpha 1d adrenoceptor clones. Therefore the classical alpha 1A-adrenoceptor appears to be the same as the expressed alpha lc-adrenoceptor clone.6. The phenylephrine contractions in the spleen were competitively antagonized by WB 4101 (pA2 8.1),5-methyl-urapidil (pA2 7.1), phentolamine (pA2 7.3), benoxathian (pA2 7.4), spiperone (pA2 7.9),indoramin (pA2 7.5) and BMY 7378 (pA2 7.4), consistent with the affinities of these antagonists in binding studies on tissue alB-adrenoceptors. The pA2 values correlated best with the published affinities of these compounds on the expressed alb-adrenoceptor clone and poorly with those at either the expressed alpha ld- or alpha lc-adrenoceptor clones. Therefore the alpha lB-adrenoceptor appears to be the same as the expressed alpha lb-adrenoceptor clone.7. The results provide pharmacological evidence that the alpha1-adrenoceptor mediating noradrenaline contractions in the epididymal portion of the rat vas deferens is the alpha 1A-(alpha lC) subtype and that contractions to phenylephrine in the rat spleen are mediated by the alpha 1B-subtype.

Adrenergic alpha-Agonists↗

The effect of posture on airway caliber with the sleep-apnea/hypopnea syndrome.

Snoring and sleep apnea are more common in the supine than seated position. We therefore studied the effect of posture on upper-airway caliber in normal subjects, snorers, and subjects with the sleep-apnea/hypopnea syndrome (SAHS). We measured upper-airway cross-sectional area by acoustic reflection in 110 SAHS patients (apnea/hypopnea index [AHI] > 15), 70 snorers without SAHS (AHI < 15), and 40 male controls matched for body-mass index (BMI) to the 40 SAHS patients. SAHS patients in the seated position had smaller upper-airway areas at the orophyngeal junction (OPJ) than either the snorers (p < 0.01) or the normal subjects (p < 0.02), but there were no differences between groups in airway cross-sectional areas in the supine or lateral recumbent positions. SAHS patients had significantly smaller decreases in OPJ area from the seated to either the supine (p < 0.001) or lateral recumbent (p < 0.001) positions than did the snorers. SAHS patients also had smaller (p < 0.05) decreases in OPJ area upon lying down than did the BMI-matched normal subjects. These data are compatible with SAHS patients defending their upper airway more upon lying down than do snorers or normal subjects.

Acoustics↗

Alpha 1-adrenoceptor subtypes in the human prostate.

OBJECTIVE: To determine the subset of alpha 1-adrenoceptors mediating the functional abstraction of the prostate to noradrenaline. MATERIALS AND METHODS: Radioligand experiments were performed with membranes prepared from rat 1 fibroblasts transfected with rat alpha 1a, hamster alpha 1b or bovine alpha 1c adrenoceptor cDNA. Human prostatic tissue obtained from transurethral resection of the prostate with full informed consent was submitted to functional in vitro muscle strip experiments. RESULTS: The binding experiments defined the potential subtype selectivity of various antagonists. Using this information, it was possible to define the functionally important alpha 1-adrenoceptor subtype in the human prostate. CONCLUSION: This work reports the results of the first functional characterization of the alpha 1c-adrenoceptor subtype. The most functionally important alpha 1-adrenoceptor type in the human prostate appears to be the alpha 1c subtype. This finding may aid the development of prostate-selective adrenoceptor pharmacotherapy.

Adrenergic alpha-Antagonists↗

Effect of posture on upper airway dimensions in normal human.

Posture has a major effect on breathing during sleep. Snoring, hypopneas, and apneas are all more common lying than sitting and more common supine than in a lateral lying position. Because the effect of the lateral lying position on upper airway caliber has not previously been studied, we examined this in 20 normal awake subjects and also determined the effect of neck position. The acoustic reflection technique was used. Pharyngeal cross-sectional areas (CSA) fell significantly from the sitting to supine position (oropharyngeal junction, from 1.65 +/- [SEM] 0.6 cm to 1.31 +/- 0.07 cm), but there was no difference in CSA between the supine and lateral positions for oropharyngeal junction (1.36 +/- 0.06 cm), mean pharyngeal area, maximal pharyngeal area, or pharyngeal volume. Neck hyper-extension significantly increased pharyngeal CSA (e.g., oropharyngeal junction null position 1.51 +/- 0.08, hyper-extension 1.94 +/- 0.11 cm), but there was no significant effect of neck flexion on airway CSA. These results confirm that in normal awake subjects, pharyngeal areas are smaller lying than sitting but also showed no significant difference between CSA in the supine and lateral lying positions. The study also demonstrates that the upper airway caliber increases with neck extension in conscious adults.

Acoustics↗

Minimal cross-sectional areas, nasal peak flow and patients' satisfaction in septoplasty and inferior turbinectomy.

Changes in minimal cross-sectional areas, measured by acoustic rhinometry as well as nasal peak flow fractions and linear analogue patients' satisfaction scores, were measured in two groups of eight patients each, undergoing septoplasty alone and septoplasty combined with trimming of the inferior turbinates, respectively. Patients who had both procedures performed showed the greatest increase in both minimal cross-sectional areas and peak flow fractions, and both of these parameters were closely correlated with patients' satisfaction, whether the patient was satisfied or not. Pre-operative nasal obstruction was worse in the dual-procedure group, but post-operative satisfaction was significantly greater in these patients. Both acoustic rhinometry and nasal peak flow fractions can be recommended as accurate and easy to perform pre-operative measurements in patients undergoing surgery for nasal obstruction.

Adolescent↗

Biosynthesis of isoprenoid compounds in Schistosoma mansoni.

The isoprenoid biosynthetic capacity of digenetic trematodes was investigated by following the fate of [14C]mevalonic acid incorporated by Schistosoma mansoni during maintenance in axenic culture. Isoprenoid compounds were analyzed by thin-layer chromatography and high-performance liquid chromatography. Of the nonsaponifiable lipid classes, radioactivity was recovered in the dolichols, ubiquinones and in the short-chain isoprenoid alcohols. The latter group of lipids included geraniol, farnesol, geranylgeraniol and a compound tentatively identified as 2,3-dihydrogeranylgeraniol. Radioactivity derived from [14C]mevalonate was also incorporated into the saponifiable lipids, with 2,3-dihydrogeranylgeranoic acid accompanied by much less geranylgeranoic acid being detected in the triacylglycerol-containing fraction. Similarly, geranylgeraniol and the dihydro derivative were also detected as esters, presumably with fatty acids. The possible significance of the results is discussed.

Alcohols↗

The potential of vervet monkeys (Cercopithecus aethiops) and baboons (Papio anubis) as models for the study of the immunology of Echinococcus granulosus infections.

Nine vervet monkeys and nine baboons were infected with eggs of Echinococcus granulosus per os. Six of the vervets and one of the baboons possessed hydatid cysts at autopsy, 15-28 months post-infection. The sequential IgG response to hydatid fluid and protoscolex antigens showed considerable inter-animal variation. Infected vervets and baboons became seropositive after an average of 8 months post-infection. Considerable fluctuation in the IgG response was observed, particularly to the hydatid fluid antigen which, in humans, may contribute to the existence of a significant proportion of seronegative individuals. Vervets, in particular, may be useful to study immunological events associated with exposure, development and resolution of hydatid disease in outbred human populations.

Animals↗

Acoustic reflectometry for airway measurements in man: implementation and validation.

A practical implementation of acoustic reflectometry for determining airway areas in routine clinical use is described. Advances over previous systems include portability, free breathing during measurements, no need to equilibrate with helium/oxygen, and real-time display of airway areas. Validation of the reflectometer with an airway model gave accuracies and reproducibilities (coefficient of variation (CV)) in the range 5-10%. With human volunteers, the within-run CV was typically 10%, and the day-to-day CV was 20%. The effect of breathing pattern on airway areas is demonstrated. In ten normal volunteers, acoustic and magnetic resonance imaging (MRI) methods of assessing pharyngeal and glottal areas were compared. The results (mean +/- SD) for the oropharynx were 1.0 +/- 0.3 cm2 acoustically and 0.9 +/- 0.5 cm2 by MRI (p = 0.77). The corresponding figures for glottal areas were 1.3 +/- 0.3 cm2 and 1.1 +/- 0.4 cm2 (p = 0.09).

Humans↗

The performance of the Rigiscan in the measurement of penile tumescence and rigidity.

The validity of the Rigiscan as a measure of both penile circumference and rigidity was assessed. In the first study, the Rigiscan was used simultaneously with a mercury-in-rubber strain gauge to monitor nocturnal penile tumescence. The Rigiscan was found to underestimate the circumference proportional to the degree of erection. In a second study a calibration system was developed which allowed independent variation of circumference and rigidity. Assessment of the Rigiscan with this system confirmed that circumference was underestimated, particularly at lower levels of rigidity, and also that different devices consistently recorded different degrees of rigidity. The use of this type of system for regular calibration is recommended, and other potential improvements in the device for research purposes are discussed.

Adult↗

Nitric oxide synthesis inhibitors attenuate calcitonin gene-related peptide endothelium-dependent vasorelaxation in rat aorta.

The effect of inhibitors of nitric oxide synthesis were examined on the endothelium-dependent relaxation induced by acetylcholine and human alpha-calcitonin gene-related peptide (CGRP) on rat isolated aortic rings preconstricted with noradrenaline. The endothelium-dependent vasorelaxation induced by acetylcholine and CGRP was inhibited by NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (L-NOARG) in a concentration-related fashion. The inhibition of endothelium-dependent relaxation by L-NMMA and L-NOARG was partially reversed by L-arginine but not by D-arginine for both acetylcholine and CGRP. The data presented suggests that CGRP, like acetylcholine; relaxes the rat aorta via the release of nitric oxide.

Acetylcholine↗