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Biomedical subjects

M A Adams

Publications and source records attributed to M A Adams.

At least 73 records · Page 4Linked to original sources
PubMed1997

Preliminary assessment of potential health hazards associated with barium leached from glazed ceramicware.

Ceramic glazes contain several elements which have the potential to leach into food or beverages that are held or stored in ceramicware. Recently, barium salts have been investigated as one of the alternatives to lead in frit formulations for glazes. This preliminary evaluation addresses the potential health hazards associated with barium at levels that might leach from glazed ceramicware. A set of specialty ceramicware, consisting of five teacups and a pitcher, was examined for extractable barium. Exposure to barium that adults (18-44 years) might encounter using the vessels for coffee, tea, or orange juice was estimated. The exposure estimate was derived from values for intakes of the beverages and for the barium migration from glazed ceramicware test samples. An established reference dose (RfD) for barium exposure for the critical effect of hypertension was identified. The potential hazard associated with the leaching of barium from glazed ceramicware varied with the level of use. Consuming beverages in amounts up to the 95th percentile would not result in total barium intake in amounts that exceed the RfD; consuming large quantities (> 95th percentile) of beverages such as tea or coffee from glazed vessels might. This suggests that for a small portion of the population of users, intake of barium may be in quantities that warrant further consideration as a potential health hazard. Analyses of a broad sample of ceramicware and study of barium leaching behaviour under actual use conditions are needed to assess further the significance of these findings.

Adolescent↗
PubMed1997

Long-term inhibition of the renin-angiotensin system in genetic hypertension: analysis of the impact on blood pressure and cardiovascular structural changes.

OBJECTIVE: To compare, using data from published studies, the efficacy of chronic inhibition of the renin-angiotensin system in inducing persistent downregulation of hemodynamic and cardiovascular structural changes in an adult rat with established genetic hypertension with the widely accepted known downregulation in young genetically hypertensive rats. STUDY SELECTION: We report on 36 studies that satisfied our inclusion criteria (angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist treatment that lowered arterial pressure levels for at least 3 weeks). Of the 24 studies concerning developing hypertensive rats, a significant number (n = 17) also examined the persistence of any hemodynamic or cardiovascular effects after withdrawal of treatment. Conversely, of 15 studies using adult rats only seven and three reported on post-treatment hemodynamic and cardiovascular structural indices respectively. RESULTS: During treatment the hemodynamic and cardiovascular structural changes produced were qualitatively and quantitatively similar in the young and adult treated rats. Critical assessment of the persistence of these effects after withdrawal of treatment again found qualitatively similar responses. However, the strength of this finding is limited by the paucity of studies concerning adult rats in which equivalent treatment durations and equipressor doses of treatments were compared between these two age groups. CONCLUSIONS: Blockade of the renin-angiotensin system appears to have an efficacy in reversing established hypertension and hypertrophy similar to that with which it prevents the development of hypertension and hypertrophy. This partial 'cure' of hypertension after withdrawal of treatment is clearly evident when treatment is initiated during the development of hypertension and appears to be similar even when treatment is initiated in established hypertension.

Angiotensin Receptor Antagonists↗
PubMed1997

Inhibition of nitric oxide in rats. Regulation of cardiovascular structure and expression of insulin-like growth factor I and its receptor messenger RNA.

OBJECTIVE: To determine whether 12 days' treatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, in spite of the increased arterial load, resulted in a growth-inhibitory response in the heart, aorta and skeletal muscle vascular bed, and whether the presence of L-NAME affected the expression of insulin-like growth factor-I and its receptor messenger RNA (mRNA). METHODS: Wistar rats were treated orally either with 100 mg/kg L-NAME or with tap water. On days 2, 4, 7 and 12 after initiation of treatment, the systolic blood pressure/mean arterial blood pressure and heart rate were measured, rats were killed and their heart and aorta were excised. Insulin-like growth factor-I and its receptor mRNA were quantitated by solution hybridization assay. On day 12 resistance properties in the skeletal muscle vascular bed were measured by using an in-vivo constant-flow preparation. RESULTS: The blood pressure in L-NAME-treated rats was increased immediately after initiation of treatment and it continued to increase throughout the experimental period. No hypertrophy was noted in the heart. Moreover, a 21% (P < 0.05) decrease in the right: left ventricular weight ratio indicated that attenuation of growth of the right ventricle had occurred. Increased expression of insulin-like growth factor-I and its receptor mRNA was observed neither in the heart nor in the aorta. The skeletal muscle vascular bed showed a 26% increased resistance at maximal vasodilatation (P < 0.05), which was indicative of a reduced average lumen size. A lower than expected perfusion pressure at maximal vasoconstriction was observed (17% above control, P < 0.05), implicating only modest medial thickening. CONCLUSION: L-NAME hypertension caused a prompt increase in blood pressure, which led neither to left ventricular hypertrophy nor to the expected overexpression of left ventricular/aortic insulin-like growth factor-I mRNA and only to partial structural adaptation in the skeletal muscle vasculature. These findings suggest that augmented expression of insulin-like growth factor-I and its receptor could be mandatory for conveying an appropriate adaptive hypertrophic response, at least in the heart.

Animals↗
PubMed1997

The persistent effect of long-term enalapril on pressure natriuresis in spontaneously hypertensive rats.

Long-term angiotensin-converting enzyme inhibitor treatment has been shown to have a persistent antihypertensive effect in spontaneously hypertensive rats (SHR) long after discontinuation of treatment. To test the hypothesis that this persistent effect involves a shift in the pressure-natriuresis relation, we performed experiments in male, anesthetized SHR at 18 wk of age with fixed neural and hormonal influences on the kidney. Renal function was assessed at various levels of arterial pressure using standard clearance techniques. Enalapril (25 mg.kg-1.day-1 in drinking water) was administered from 4 to 14 wk of age and again 3 days before renal function studies. The following four groups of SHR were studied: 1) 10-wk treatment, 2) 10-wk + 3-day treatment, 3) 3-day treatment, and 4) untreated. Groups 1 and 4 had an intact renin-angiotensin system; groups 2 and 3 had the renin-angiotensin system blocked. Mean arterial pressure (MAP, mmHg; means +/- SE) under Inactin anesthesia was 139 +/- 4 (n = 9), 109 +/- 3 (n = 8), 149 +/- 1 (n = 9), and 181 +/- 7 mmHg (n = 9) for each of the four groups, respectively. Glomerular filtration rate was similar in all groups at resting levels of MAP, whereas renal blood flow was elevated in all treatment groups when compared with that in untreated SHR. Pressure-natriuresis, pressure-diuresis, and pressure-fractional sodium excretion curves for the 10-wk treatment group and 3-day only treatment group were shifted leftward to significantly lower pressures by approximately 25 mmHg, compared with the untreated group. The curves for the treated +3-day group were shifted an additional 30 mmHg to the left. The relationship between renal artery pressure (RAP) and renal interstitial hydrostatic pressure was also shifted 25-30 mmHg but only in rats that received the long-term treatment with enalapril. Three-day enalapril had no significant effect on this relationship. These data indicate that the persistent effect of long-term enalapril treatment on arterial pressure in SHR is the result of a shift in the pressure-natriuresis relationship. The mechanism for this effect involves hemodynamic changes that act to improve transmission of RAP to the interstitium, resulting in enhanced sodium excretion for a given level of RAP.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Induction of growth hormone receptor and insulin-like growth factor-I mRNA in aorta and caval vein during hemodynamic challenge.

Induction of two-kidney, one clip hypertension (renal hypertension) is characterized by a slow increase in left ventricular tension and aortic wall stress, as opposed to aortocaval fistula or shunt volume overload, which induces a marked and rapid onset of wall stress in the caval vein and right ventricle. In the present study, we applied hemodynamic challenge to study the growth response involving gene expression of insulin-like growth factor-I (IGF-I) and growth hormone receptor (GH-R) mRNA in aorta and caval vein. Volume overload and pressure overload were induced in Wistar rats by means of shunt and renal hypertension, respectively. Systolic pressure was measured before excision of the great vessels, which was performed between 2 and 12 days postoperatively. Aortic and caval vein IGF-I and GH-R mRNA expressions were measured by means of a solution hybridization assay, and the caval vein was analyzed for IGF-I protein by immunohistochemistry. In the volume-distended but not pressurized caval vein in shunt rats, verified by telemetry recordings, there was an eightfold increase in IGF-I and 3.5-fold increase in GH-R mRNA at day 4 versus control. The IGF-I protein appeared to be localized in smooth muscle cells. In the aorta of the renal hypertension group, changes were of a slower onset. At day 7, there was a fourfold increase in IGF-I and five-fold increase of GH-R mRNA expressions versus sham-operated rats. Both the shunt caval vein and renal hypertension aorta showed evidence of a structural adaptation of the growth response. The present study suggests that acute elevation in vascular wall stress is an important triggering factor for overexpression of IGF-I and GH-R mRNA in great vessels. The growth hormone/insulin-like growth factor axis may be an important link in mediating structurally adaptive growth responses in the blood vessel wall.

Animals↗
PubMed1997

Neonatal angiotensin-converting enzyme inhibition in the rat induces persistent abnormalities in renal function and histology.

Recently, we reported that neonatal blockade of the renin-angiotensin system in the rat produces irreversible abnormalities in renal histology associated with increased diuresis. In the present study, we assessed the long-term consequences of neonatal angiotensin-converting enzyme inhibition on renal function. Rats were injected with 10 mg.kg-1.d-1 enalapril or vehicle from day 3 to day 24 after birth. Urine concentrating ability, renal function, and renal histology were assessed in 16-week-old rats. There was a twofold increase in diuresis and water intake in enalapril-treated rats throughout the study course. Urine osmolality after 24 hours of water deprivation was 1008 +/- 108 and 2549 +/- 48 mOsm.kg-1 (P < .05) in enalapril- and vehicle-treated rats, respectively. Glomerular filtration rate (0.54 +/- 0.03 versus 0.75 +/- 0.06 mL.min-1x100 g body wt-1, P < .05) and effective renal plasma flow (1.76 +/- 0.09 versus 2.19 +/- 0.14 mL.min-1x100 g body wt-1, P < .05) were reduced in neonatally enalapril-treated versus control rats. Absolute and fractional urinary sodium excretion values were elevated (P < .05) in enalapril-treated rats. Semiquantitative assessment of renal histology demonstrated statistically significant degrees of papillary atrophy, interstitial fibrosis and inflammation, tubular atrophy and dilatation, and focal glomerulosclerosis in neonatally enalapril-treated rats. In conclusion, neonatal angiotensin-converting enzyme inhibition in the rat produces irreversible alterations in renal function and morphology, demonstrating the importance of an intact renin-angiotensin system neonatally for normal renal development.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Blunted cardiovascular growth induction during prolonged nitric oxide synthase blockade.

The goal of the present study was to characterize the activation profile of the growth-related enzyme ornithine decarboxylase (ODC) in cardiovascular tissue during hypertension induced by chronic NO synthase blockade in relation to the development of structurally based changes in the heart and blood vessels. In previously instrumented conscious rats, mean arterial pressure and ODC activation were measured in cardiovascular tissue of rats treated with N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg per day P.O.) for 4 hours and 1, 6, and 12 days. After 12 days of L-NAME treatment alone or in combination with 3% L-ornithine, structurally based hindlimb resistance properties were assessed. A marginal activation of ODC in the left ventricle and aorta was seen at 4 hours but returned to control levels at 1, 6, and 12 days of L-NAME treatment. A slightly prolonged yet transient activation of ODC occurred in the mesenteric vascular bed. Structurally based hindlimb vascular resistance was enhanced by 15% at maximum vasoconstrictor tone, and no change in cardiac mass occurred with L-NAME treatment. L-NAME+3% L-ornithine treatment resulted in a similar level of structural upregulation compared with L-NAME treatment alone. In summary, 12 days of L-NAME treatment resulted in only a modest change in vascular resistance, and only at maximum constriction, and no cardiac hypertrophy despite the presence of marked hypertension. The results of the present study indicate that either (1) pressure alone is not a sufficient stimulus to induce cardiovascular growth processes or (2) L-NAME may be "nonspecifically" inhibiting cardiovascular growth processes.

Animals↗
PubMed1996

Psychological questionnaires: do "abnormal" scores precede or follow first-time low back pain?

STUDY DESIGN: A prospective study of psychological risk factors for first-time low back pain with repeated use of psychological questionnaires. OBJECTIVES: To measure the reproducibility of scores from psychological questionnaires, and to compare this with changes that follow an individual's first attack of back pain. Secondly, to determine which scores predict first-time back pain. SUMMARY OF BACKGROUND DATA: "Abnormal" psychometric scores are associated with several aspects of back pain behavior. Little is known, however, about their reproducibility or long-term stability, and there has been no definitive answer to the question: which comes first, "abnormal" scores or low back pain? METHODS: 403 volunteers with no history of "serious" low back pain (defined as pain requiring medical attention or absence from work) participated in a functional spinal assessment. At the time of initial assessment and at 6-month intervals thereafter, the volunteers completed the following questionnaires: the Health Locus of Control, which was subdivided into three sections labelled "Internal," "Powerful others," and "Chance"; the Modified Somatic Perception Questionnaire; and the Zung depression scale. Scores from the Modified Somatic Perception Questionnaire and from the Zung depression scale were added to form a measure of psychological distress. Additional questionnaires inquired about any back pain experienced in the previous 6 months. Only three volunteers had left the study at the 18-month follow-up. At that time 162 participants had reported "any" low back pain, of which 79 were "serious." RESULTS: Intraclass correlation coefficients for scores repeated after 6 months ranged from 0.67-0.80, and reproducibility of scores was equally high between the 0-, 6-, 12- and 18-month assessments. None of the scores were affected by "any" low back pain, and only the Modified Somatic Perception Questionnaire scores changed after "serious" back pain was reported. In a multivariate analysis, the most significant predictor of first time "serious" or "any" back pain was a history of non-"serious" back pain (P < 0.001). Of the psychological factors, the sum of Modified Somatic Perception Questionnaire scores and Zung questionnaire scores was the best predictor of "serious" back pain (P = 0.037), and the Modified Somatic Perception Questionnaire score was the best predictor of "any" back pain (P = 0.002). The 25% of participants with the highest sum of scores from the Modified Somatic Perception Questionnaire and Zung questionnaire was 2.7 times more likely to develop "serious" back pain than the 25% with the lowest sum of these scores. Nevertheless, after accounting for the affects of a history of non-"serious" back pain, psychometric scores predicted less than an additional 3% of reported back pain. CONCLUSIONS: The scores from the Modified Somatic Perception Questionnaire and Zung questionnaire were reproducible over 18 months and were affected little by first episodes of back pain; yet these scores were significant predictors of it. "Abnormal" scores from these questionnaires precede back pain in a small number of people.

Adolescent↗
PubMed1996

Sustained loading generates stress concentrations in lumbar intervertebral discs.

STUDY DESIGN: Cadaveric motion segment experiment. Measurements on each specimen were compared before and after creep loading. OBJECTIVES: To show how sustained "creep" loading affects stress distributions inside intervertebral discs. SUMMARY OF BACKGROUND DATA: The central region of an intervertebral disc acts like a hydrostatic "cushion" between adjacent vertebrae. However, this property depends on the water content of the tissues and may be lost or diminished after creep. METHODS: Twenty-seven lumbar motion segments consisting of two vertebrae and the intervening disc and ligaments were loaded to simulate erect standing postures in life. The distribution of compressive stress in the disc matrix was measured by pulling a miniature pressure transducer through the disc in the midsagittal plane. Profiles of vertical and horizontal compressive stress were repeated after each specimen had been creep loaded in compression for 2-6 hours. RESULTS: Creep reduced the hydrostatic pressure in the nucleus by 13-36%. Compressive stresses in the anulus were little affected when the profiles were measured at 1 kN, but at 2 kN, localized peaks of compressive stress appeared (or grew in size) in the posterior anulus after creep. CONCLUSIONS: Increased loading of the apophysial joints causes an overall reduction in intradiscal stresses after creep. In addition, water loss from the nucleus causes a transfer of load from nucleus to anulus. Stress concentrations may lead to pain, structural disruption, and alterations in chondrocyte metabolism. Disc mechanics depend on loading history as well as applied load.

Adult↗
PubMed1996

Time-dependent changes in the lumbar spine's resistance to bending.

OBJECTIVE: To show how time-related factors might affect the risk of back injury. DESIGN: Mechanical testing of cadaveric lumbar motion segments. BACKGROUND: High bending stresses acting on the lumbar spine are associated with injuries to the intervertebral discs and ligaments. Since these soft tissues are viscoelastic, the bending stress ('bending moment') must depend on the speed of movement and the duration of loading, but this has not previously been quantified. METHODS: Forty-five cadaveric lumbar segments, consisting of two vertebrae and the intervening disc and ligaments, were loaded in combined bending and compression in order to simulate movements and postures in living people. The relationship between flexion angle and bending moment was determined at different loading rates, and after sustained loading in bending and in compression. RESULTS: Rapid flexion movements increased the peak bending moment by 10-15% compared to slow movements. On average, repeated flexion over a period of 5 min reduced the peak bending moment by 17%, and 5 min of sustained flexion reduced it by 42%. Two hours of compressive creep loading reduced the height of the intervertebral discs by 1.1 mm, increased the range of flexion by 12%, and reduced peak bending moment by 41%. CONCLUSIONS: The scale of these changes suggests that, in life, the risk of bending injury to the lumbar discs and ligaments will depend not only on the loads applied to the spine, but also on loading rate and loading history. RELEVANCE: The results show how time-dependent factors can increase the risk of bending injury to the osteoligamentous lumbar spine.

Journal Article↗
PubMed1996

Hypertension without cardiac hypertrophy does not induce a cardiac baroreflex deficit.

OBJECTIVE: To investigate the effects of prolonged hypertension in the absence of cardiac hypertrophy on the blood pressure-heart rate reflex during acute and chronic NO synthase blockade. METHODS: Male Wistar rats were treated acutely with N omega-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg intraperitoneally) or chronically with L-NAME (2.5-3 weeks, 50 mg/kg per day orally). The cardiac baroreceptor reflex was assessed in previously instrumented conscious rats by using a 'steady-state' method that involved alternating vasoactive drug-induced stepwise increases and decreases in mean arterial pressure with methoxamine and sodium nitroprusside. Following baroreflex assessment, the rats were killed by an overdose of anaesthetic, their hearts were removed and the left ventricle plus septum separated from the heart and weighed. RESULTS: The arterial pressure at one-half of the heart rate range was shifted to higher arterial pressures, consistent with the increase in the operating point of mean arterial pressure following NO synthase blockade. No change in any of the baroreflex parameters could be detected despite prolonged L-NAME-induced hypertension. On the basis of the study criteria, the data from one rat were not included in the group analysis because of the presence of cardiac hypertrophy. CONCLUSIONS: The results of the present study indicate that increased blood pressure alone, either acutely or chronically, is not a sufficient stimulus to induce a baroreflex deficit.

Animals↗
PubMed1996

Effect of sustained loading on the water content of intervertebral discs: implications for disc metabolism.

OBJECTIVE: To examine regional changes in the fluid content of human intervertebral discs by comparing sagittal plane "profiles" of hydration before and after mechanical loading. METHODS: Cadaveric lumbar intervertebral discs were loaded to simulate a typical day's loading in vivo. Ten motion segments were subjected to a 1500 N compressive load for a period of 6 h with the superior vertebrae inclined by 4-8 degrees to simulate a slightly flexed posture. Immediately after loading the discs were frozen at -80 degrees C. Subsequently they were cut into slices perpendicular to the sagittal midline of the disc, and each slice was weighed before and after freeze drying. This enabled a profile of fluid content across the disc to be constructed. Fluid loss due to loading was estimated by comparing the water content of each loaded disc with that of an adjacent unloaded disc from the same spine. RESULTS: After 6 h of creep loading, disc height approached, but did not quite reach, an equilibrium. The mean fluid loss from all discs was 18%. All regions except the outer 2 mm experienced a significant loss of fluid (P < 0.01). The posterior mid-annulus showed the greatest fluid loss (30%), while the nucleus lost 15%. CONCLUSIONS: A comparison with previously published work suggests that fluid exchange of this magnitude will have a considerable effect on disc cell metabolism and on metabolite transport.

Adult↗
PubMed1996

Stress distributions inside intervertebral discs: the validity of experimental "stress profilometry'.

This paper evaluates a technique for measuring the distribution of compressive stress within cadaveric intervertebral discs. A strain-gauged pressure transducer, side-mounted near the tip of a 1.3 mm diameter needle, was inserted into cubes of disc tissue and into intact discs. Regardless of the position and orientation of the transducer within the tissue or disc, its output was found to be proportional to the compressive force applied to the specimen. The distribution of compressive stress was measured by pulling the instrumented needle through the specimen and the resulting stress profiles were reproducible to within 20 per cent. Profiles obtained at different applied loads showed a similar distribution of stress within the disc, suggesting that the compressive stress at any location and direction increased in proportion to the applied load. Since transducer output was also proportional to applied load, it was reasoned that it must be proportional to compressive stress within the disc. The average vertical compressive stresses acting on various regions within a disc were calculated from the stress profiles and multiplied by the cross-sectional area of each region: the resulting force was then compared with the known applied force in order to assess the calibration coefficient of the transducer. Agreement between the two forces was good, indicating that the calibration coefficient established in a saline bath was applicable to disc tissues also. However, artifactual stress peaks could be generated if the transducer was pulled across a bony asperity. It is concluded that the transducer measures the mean compressive stress acting upon it within disc tissues. Errors associated with the technique are small compared to differences in stress distributions which occur naturally, for example when intervertebral discs are loaded to simulate different postures in a living person.

Adult↗
PubMed1996

'Stress' distributions inside intervertebral discs. The effects of age and degeneration.

We investigated the distribution of compressive 'stress' within cadaver intervertebral discs, using a pressure transducer mounted in a 1.3 mm diameter needle. The needle was pulled along the midsagittal diameter of a lumbar disc with the face of the transducer either vertical or horizontal while the disc was subjected to a constant compressive force. The resulting 'stress profiles' were analysed in order to characterise the distribution of vertical and horizontal compressive stress within each disc. A total of 87 discs from subjects aged between 16 and 87 years was examined. Our results showed that age-related degenerative changes reduced the diameter of the central hydrostatic region of each disc (the 'functional nucleus') by approximately 50%, and the pressure within this region fell by 30%. The width of the functional annulus increased by 80% and the height of compressive 'stress peaks' within it by 160%. The effects of age and degeneration were greater at L4/L5 than at L2/L3, and the posterior annulus was affected more than the anterior. Age and degeneration were themselves closely related, but the stage of degeneration had the greater effect on stress distributions. We suggest that structural changes within the annulus and endplate lead to a transfer of load from the nucleus to the posterior annulus. High 'stress' concentrations within the annulus may cause pain, and lead to further disruption.

Adolescent↗
PubMed1996

Coronary artery bypass graft surgery and its impact on erectile function: a preliminary retrospective study.

Erectile function is markedly affected by acute alterations in circulatory homeostasis of which coronary artery bypass graft surgery is an excellent model. A group of consecutive patients who had undergone coronary artery bypass surgery 6-12 months previously were selected for detailed review by questionnaires that scored their pre-operative and post-operative sexual function and erectile ability and aspects of the quality of life. Thirty patients were evaluable. 10 men (33.3%) had poor erectile function before surgery. Eleven out of 30 men reported an improvement in erectile function while 10 men experienced a decrease or cessation of erectile function. Four of the five patients reporting new post-operative erectile function had had good pre-operative function suggesting that the surgery was directly associated with the impotence in these men. This pilot study suggests that coronary artery bypass surgery can have a significant impact in erectile function.

Coronary Artery Bypass↗
PubMed1996

Acute hypertension after nitric oxide synthase inhibition is mediated primarily by increased endothelin vasoconstriction.

OBJECTIVE: To determine the quantitative roles played by the different vasoconstrictor systems in the acute pressor response in conscious rats before and after inhibition of nitric oxide synthase with Nw-nitro-L-arginine methyl ester (L-NAME). METHODS: In conscious male Sprague-Dawley rats, previously instrumented with aortic and venous catheters, the contributions of the different systems were assessed by maximal cumulative pharmacological blockade of alpha 1-adrenoceptors (1 mg/kg prazosin intraperitoneally), AT1 receptors (30 mg/kg losartan intraperitoneally) and V1/V2 receptors (10 mg/kg [beta-mercapto-beta, beta-cyclopenta-methylenepropionyl1, O-Et-Tyr2-Val4-Arg8]-vasopressin per min intravenously). In addition, the contribution of endothelin-1-induced vasoconstriction in response to 100 mg/kg L-NAME intraperitoneally to the hypertension was assessed by administering 5-100 mg/kg ETA/ETB receptor antagonist PD 145 065 intravenously under three different conditions: as the last step of a series of antagonists in the cumulative pharmacological blockade after having induced the L-NAME pressor response; alone before L-NAME treatment; and alone after the full development of the L-NAME pressor response. A separate group of rats was treated acutely with 30 mg/kg losartan intraperitoneally or pretreated for 3 days with 30 mg/kg angiotensin I converting enzyme inhibitor enalapril via drinking water alone or in combination with 1% salt was used to assess the role of the renin-angiotensin system in the L-NAME-induced hypertension. RESULTS: Short-term administration of the combined ETA/ETB receptor antagonist PD 145065 did not change the arterial pressure under control conditions. Inhibition of the renin-angiotensin system, alpha 1-adrenoceptors or vasopressin receptors alone or in combination did not alter the magnitude of the L-NAME pressor response. In contrast, our results show that both treatments before and during acute nitric oxide synthase blockade hypertension using the ETA/ETB receptor antagonist PD 145065 abolished almost completely (approximately 85%) the pressor response. CONCLUSIONS: These studies indicate that the predominant mechanism of hypertension, at least in the acute phase, after acute nitric oxide synthase blockade with L-NAME is associated with a marked increase in ETA/ETB receptor activation rather than with increases in alpha 1, AT1 and V1/V2 receptor activation. It remains to be determined whether endothelin participates also in the chronic phase of nitric oxide-deficient hypertension.

Animals↗
PubMed1995

Mechanical testing of the spine. An appraisal of methodology, results, and conclusions.

The purpose of this report was to assess various methods of testing the mechanical properties of the spine and to suggest those most appropriate for particular applications. Questions addressed include the following: Are cadaveric experiments a reliable guide to mechanical properties in-vivo? Is it better to test "motion segments" or larger sections of spine? Is it necessary to simulate forces from individual muscles? How high should the applied forces be? The results of some recent experiments are described to indicate the potential of the techniques available.

Animals↗