Biomedical subjects

D A Taylor

Publications and source records attributed to D A Taylor.

At least 73 records · Page 4Linked to original sources

PubMed1997

Classification of pain following spinal cord injury.

Pain continues to be a significant management problem in people with spinal cord injuries. Despite this there is little consensus regarding the nature, terminology and definitions of the various types of pain that occur following spinal cord injury. This has led to large variations in the reported incidence and prevalence of pain following spinal cord injury. Treatment studies have been hampered by inconsistent and inaccurate identification of pain types. We believe that both research and management would benefit from an agreed upon classification system which accurately and reliably identifies the types of pain that occur following spinal cord injury. We have reviewed the literature on the classification of pain following spinal cord injury and have developed a classification system which adopts the strengths of previous systems and attempts to avoid the weakness inherent in others. Our proposed classification system of pain following spinal cord injury includes four major divisions: musculoskeletal, visceral, neuropathic and other types of pain. We have divided neuropathic pain on the basis of region into two subdivisions: neuropathic at level and neuropathic below level pain. We have further divided neuropathic at level pain into two categories: radicular and central, to indicate the presumed site of the lesion responsible for pain generation. We believe that our proposed classification system is comprehensive, simple and readily applicable in the clinical and research situation. It is our hope that this proposed classification will contribute to the eventual development of a universal system for the classification of pain following spinal cord injury.

Humans↗

PubMed1997

Reduced effects of L-carnitine on glucose and fatty acid metabolism in myocytes isolated from diabetic rats.

Depressed glucose utilization and over-reliance of muscle tissues on fat represents a major metabolic disturbance in diabetes. This study was designed to investigate the relationship between fatty acid oxidation and glucose utilization in diabetic hearts and to examine the role of L-Carnitine on the utilization of these substrates in diabetes. 14CO2 release from [1-14C]pyruvate (an index of PDH activity), [2-14C]pyruvate and [6-14C]glucose (an index of acetyl-CoA flux through the Krebs cycle), [U-14C]glucose (an index of both PDH and acetyl-CoA flux through the Krebs cycle), and [1-14C]palmitate oxidation were studied in cardiac myocystes isolated from normal and streptozotocin-injected rats. Palmitate oxidation was increased twofold in diabetic myocytes compared to normal cells (5.4 +/- 1.45 vs 2.35 +/- 0.055 nmol/mg protein/30 min, p > 0.05). L-Carnitine (5 mM) significantly increased palmitate oxidation (60-70%) in normal cells but had no effect on diabetic cells. The activity of PDH and acetyl-CoA flux through the Krebs cycle was severely depressed in diabetes (58.14 +/- 20.27 and 8.63 +/- 0.62 in diabetes vs 128.75 +/- 11.47 and 24.84 +/- 7.81 nmol/mg protein/30 min in controls, p > 0.05, respectively). The efflux of acetylcarnitine, a by-product of PDH activity was also much lower in diabetic cells than in normal cells but had no effect in diabetes. L-Carnitine also had no effect on 14CO2 release from [U-14C]glucose but significantly decreased that from [6-14C]glucose, which reflects oxidative metabolism suggesting that L-Carnitine decreases oxidative glucose utilization. Thus, these data suggest that the overreliance on fat in diabetes may be in part secondary to a reduction of carbohydrate-generated acetyl-CoA through the Krebs cycle.

Acetyl Coenzyme A↗

PubMed1997

Comparison of salmeterol and albuterol-induced bronchoprotection against adenosine monophosphate and histamine in mild asthma.

Short-acting beta(2)-agonists provide greater protection to bronchoconstriction induced by adenosine-5'-monophosphate (AMP) than does methacholine. Because AMP produces bronchoconstriction through release of mediators from mast cells, and methacholine directly constricts airway smooth muscle, this suggests that beta(2)-agonists stabilize mast cells in vivo. This in vivo property has not been demonstrated with long-acting beta(2)-agonists. We undertook two double-blind, randomized, crossover, placebo-controlled studies to investigate the effects of salmeterol and albuterol on airway responsiveness (AR) to AMP and histamine in patients with mild asthma. In the first study, 19 patients attended on four occasions to inhale salmeterol 50 micrograms or placebo 2 h before challenge with AMP or histamine. In the second study 16 patients (13 of whom had participated in the first study) were studied in a similar fashion but inhaled albuterol 400 micrograms or placebo 30 min prior to challenge. Salmeterol reduced AR to AMP and histamine by 3.4 +/- 0.3 and 3.9 +/- 0.3 doubling doses, respectively (NS). In contrast, albuterol demonstrated a greater protective effect on AMP than on histamine, reducing AR by 5.1 +/- 0.3 and 3.8 +/- 0.2 doubling doses, respectively (p < 0.005). Thus, in contrast to albuterol, salmeterol did not demonstrate mast-cell stabilizing properties in vivo at a time corresponding to maximal bronchodilatation. These findings might be explained by the unique pharmacologic profile of salmeterol in combination with the differential beta(2)-adrenoceptor pharmacology of bronchial mast cells and bronchial smooth muscle.

Adenosine Monophosphate↗

PubMed1997

Chronic morphine treatment of guinea pigs induces nonspecific sensitivity changes in the nucleus tractus solitarius in vitro.

Chronic morphine treatment results in the development of an opioid tolerance in guinea pig myenteric S-neurons that is nonspecific among pharmacologically unrelated inhibitory agonists and the concurrent development of a nonspecific super-sensitivity to unrelated excitatory agonists. The purpose of these studies was to extend this model of opioid tolerance in the guinea pig to central neurons, specifically to the medial nucleus tractus solitarius (mnTS), the primary brainstem relay for visceroceptive information. Pharmacological responses of the guinea pig mnTS neurons were examined in an in vitro brainstem slice preparation and compared between chronically morphine-treated animals and untreated controls. The spontaneous activity of guinea pig mnTS neurons was inhibited by gamma-aminobutyric acid (GABA), the GABAA-selective agonist muscimol, 2-chloroadenosine and clonidine and was excited by glutamate and elevations in extracellular potassium. Applied alone, morphine or the GABAA-selective antagonist bicuculline inhibited and excited approximately equal proportions of nucleus tractus solitarius (nTS) neurons. However, when applied in the presence of bicuculline, morphine inhibited most neurons tested. Reduced inhibitory responses to four agonists, i.e., morphine, muscimol, 2-chloroadenosine and clonidine, were observed in mnTS neurons in slices obtained from chronically morphine-treated animals. Increased excitation of these neurons by elevated extracellular potassium was observed. It is concluded that 1) guinea pig nTS neurons respond similarly to nTS neurons from other species in vitro, 2) opioids disinhibit some proportion of guinea pig nTS neurons in vitro through a GABAergic mechanism and 3) the development of opioid tolerance in guinea pig nTS neurons is qualitatively similar to that of guinea pig myenteric S-neurons.

Action Potentials↗

PubMed1997

Evidence that tolerance and dependence of guinea pig myenteric neurons to opioids is a function of altered electrogenic sodium-potassium pumping.

Ouabain acutely depolarizes most types of cells through inhibition of electrogenic Na+,K+ pumping and is a useful tool with which to study conditions that affect electrogenic pumping. Intracellular recording techniques were used with neurons of the guinea pig myenteric plexus/longitudinal muscle preparation exposed to ouabain. Of 35 S neurons exposed to ouabain (1 microM), 15 were hyperpolarized by 10 +/- 2 mV, 11 were depolarized by 8 +/- 2 mV and the remaining neurons had no change in membrane potential. The nonselective potassium channel antagonist tetraethylammonium chloride (TEA; 0.5 mM) alone evoked modest (<5 mV) and inconsistent changes in the resting membrane potential of S neurons. However, in the presence of TEA, the hyperpolarizing response to 1 microM ouabain was eliminated, and the proportion of cells depolarized by ouabain increased from 31% to 83%. Glibenclamide (10 microM) and 100 nM iberiotoxin did not change the pattern of membrane potential changes induced by 1 microM ouabain. Calcium-free buffer eliminated the hyperpolarization and potentiated the depolarization induced by 1 microM ouabain. Ouabain (5 microM), in either the presence or absence of TEA, induced depolarization in all neurons tested (mean, 15-16 mV), indicating a predominant effect of inhibition of electrogenic pumping. These data suggest that ouabain may directly or indirectly activate myenteric S neuron calcium-sensitive potassium channels as well as inhibit the Na+,K+ pump and that TEA will antagonize the former effect. Chronic exposure (morphine pellets) of guinea pigs to morphine resulted in a partial depolarized state of myenteric neurons, as previously reported. Ouabain (5 microM), either with or without TEA, depolarized neurons from chronically morphine-treated guinea pigs very little (5-6 mV) in comparison with naive neurons (15-16 mV). This supports the conclusion that the depolarized state of morphine-tolerant neurons is associated with a reduction in electrogenic Na+,K+ pumping.

Animals↗

PubMed1997

Hyperpolarizing effects of morphine, clonidine and 2-chloroadenosine in myenteric neurons associated with tolerance to morphine.

Chronic treatment of guinea pigs with morphine produces non-specific subsensitivity (tolerance) of the longitudinal smooth muscle myenteric plexus (LM/MP) preparation of the guinea pig ileum to morphine, clonidine and 2-chloroadenosine correlated with a partial depolarization of myenteric S neurons. The purpose of our investigation was to gain further evidence regarding the cellular mechanism of tolerance. Either morphine or placebo pellets were implanted s.c. in guinea pigs 7 days before the experiment. Subsensitivity was confirmed by a marked decrease of the inhibitory effect of 0.1 microM morphine and 0.3 microM clonidine on neurogenically induced twitches in longitudinal smooth muscle myenteric plexus preparations from the morphine-pretreated guinea pigs. Intracellular microelectrode recording established that only myenteric S neurons that were hyperpolarized by morphine exhibited the depolarized state (difference of 7.2 mV), which occurred without a change in the threshold for initiation of action potentials. S neurons that were hyperpolarized by superfusion with solution containing morphine, 0.1 microM, were acutely hyperpolarized an equivalent amount (6-8 mV) by clonidine, 0.3 microM, or 2-chloroadenosine, 0.1 microM. Morphine and clonidine, but not 2-chloroadenosine, reduced input resistance. The hyperpolarizations and changes in conductance were not different between tolerant and control preparations for any agonist. It is concluded that 1) the receptors for the three agonists are colocalized on selected S neurons, 2) the transduction process for the hyperpolarizing effect of 2-chloroadenosine is different than that for morphine and clonidine, 3) cross-tolerance among the agonists is not a function of altered receptors or signal transduction processes and 4) the depolarized state is associated with tolerance of myenteric S neurons.

2-Chloroadenosine↗

PubMed1997

Quantitative relation of electrocardiographic and angiocardiographic measures of risk in patients with coronary atherosclerosis. Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) Investigators.

OBJECTIVE: To correlate angiocardiographic and electrocardiographic (ECG) measures of risk in coronary artery disease (CAD) patients. SETTING: Baseline substudy of the Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT), a 2 x 2 factorial, randomized, controlled trial of CAD regression. PATIENTS: One hundred and twenty-three CAD patients, 113 males and 10 females; average age, 59 years. METHODS: Bivariate correlations of multiple quantitative measures of epicardial coronary angiographic luminal narrowing (quantitative coronary angiography [QCA]) and body surface ECG maps of the sum of the decrease in the potential time integral of the ST segment (SST decrease) between rest and symptom-limited exercise and between rest and 1 and 5 mins postexercise recovery. RESULTS: The average number of epicardial coronary segments analyzed per patient was 12. The mean diameter averaged 2.78 mm; the minimal diameter, 2.01 mm. The mean percentage coronary stenosis averaged 29.6% and the most severe averaged 62.9%. sigma ST decrease averaged -5323 microV.s between rest and peak exercise and recovered slowly, averaging -5117 microV.s at 1 min postexercise and -4562 microV.s at 5 mins. No QCA measure correlated with any ECG variable (range of r, 0.002 to -0.179; not significant). CONCLUSIONS: Among CAD patients there are no close, or causal, relations between angiographic measures of anatomic epicardial coronary atherosclerosis and ECG functional measures of exercise-induced myocardial ischemia. These data suggest that demonstrated values of stress ECG and coronary angiography for the prediction of clinical risk in CAD patients are largely independent of each other.

Coronary Angiography↗

PubMed1997

Delivery of primary autologous skeletal myoblasts into rabbit heart by coronary infusion: a potential approach to myocardial repair.

Myocardial repair after injury is limited because the adult heart cannot regenerate. We propose using autologous skeletal muscle cells (myoblasts) as a source of reserve cells for repair of regions of damaged myocardium. This report examines two potential methods for the transfer of cells to the myocardium: selective coronary catheterization, and myoblast infusion or myoblast injection directly into the left ventricular wall. Autologous, primary rabbit skeletal myoblasts were harvested, were transduced ex vivo with adenoviruses expressing the Escherichia coli beta-galactosidase (beta-gal) gene, and were infused selectively into the coronary circulation or injected directly into the myocardial wall. After either delivery method, beta-gal expression was detectable at the earliest times examined (3 days) and persisted for several weeks. The method of delivery influenced the spatial pattern of beta-gal expression. After direct injection, a localized concentration of myoblasts that decreased with distance from the injection site was visible primarily in the myocardial layer of the ventricle, although occasional staining could be detected in other layers. After coronary infusion, discrete punctate or linear foci of beta-gal expression were found throughout the distribution of the left coronary circulation in all cardiac layers. After infusion or injection, beta-gal-positive cells were seen in direct physical apposition to cardiocytes; interestingly, beta-gal could be detected also in some branched cells with clear cross-striations. Autologous myoblasts survived with no obvious dysrhythmic effects despite their presence in extensive or discrete loci in the myocardium. These observations provide the first evidence that myoblast transfer is possible by catheter-based methods, and they create the basis for studies to investigate the functional consequences of myoblast infusion in damaged heart.

Animals↗

PubMed1997

Adult patients' knowledge about their congenital heart disease.

OBJECTIVE: To assess patient knowledge about their congenital cardiovascular disease. DESIGN: Fifty consecutive patients (25 women) attending the Adult Congenital Heart Disease Clinic, University of Alberta, Edmonton, Alberta, filled out a questionnaire that tested knowledge about their heart defect and endocarditis prophylaxis. The patients ranged in age from 18 to 60 years (mean 25). The most frequent cardiovascular anomalies were obstruction of the left ventricular outflow tract (13), coarctation of the aorta (10), tetralogy of Fallot (six), transposition of the great arteries (five) and Marfan syndrome (four). Patients had been seen on average by three cardiologists (range one to six) and had made an average of seven clinic visits (range one to 22) since the age of 17 years. Eight patients had been followed at other clinics in the past. MAIN RESULTS: Fifty-four per cent of patients knew their diagnosis. Forty-four per cent could explain the defect in lay language, and another 48% made an attempt. When given a heart diagram, 26% marked their defect correctly and 28% made an attempt. Terms 'endocarditis' and 'antibiotic prophylaxis' were known to 16% and 22% of patients, respectively. Fifty-eight per cent could name at least one situation that carries a risk of 'infection in the heart'. CONCLUSION: Adults with congenital heart disease have poor knowledge of their heart defects and the importance of endocarditis and antibiotic prophylaxis. Although time consuming, patient education should be a part of every clinic visit. Repetitive and structured patient education may improve patients' knowledge and, hence, participation in their health care.

Adolescent↗

PubMed1997

Optimal dose and duration of heparin for inhibition of intimal hyperplasia.

BACKGROUND: A Dacron patch graft was placed in the common carotid artery of sheep to assess the effect of three different doses of unfractionated heparin administered for periods of one to four weeks. MATERIALS AND METHODS: Animals were divided into a control group (n=6) in which animals received a patch graft but no heparin and three main treatment groups on the basis of the dose of heparin received. Group 1 animals (n=24) received 140 units per kg daily in two divided doses. Group 2 (n=24) received 280 units per kg daily and Group 3 (n=24) received 420 units per kg daily. Each treatment group was further divided into four subgroups on the basis of the duration of treatment. Groups 1(i), 2(i), 3(i) had treatment for one week. Groups 1(ii), 2(ii), 3(ii) had treatment for two weeks. Groups 1(iii), 2(iii), 3(iii) had treatment for three weeks. Groups 1(iv), 2(iv), 3(iv) had treatment for four weeks. There were six animals in each subgroup giving a total of 72 treated sheep. Animals were sacrificed at four weeks and an intimal measurement in pm was obtained under light microscopy from a transverse sectioned segment of artery containing the patch graft using an eyepiece graticule. RESULTS: There were no haemorrhagic complications. Control animals had a mean intimal thickness of 176 pm. All treatment groups had significantly less IH--Group 1 131.9 (p<0.01), Group 2 138.5 (p<0.05), Group 3 117.8 (p<0.01). There were no significant differences between the treatment groups. There was significantly less IH in animals treated for four weeks (106.3) compared to one week (140.2, p<0.05). CONCLUSIONS: This study indicates that inhibition of IH can be achieved by heparin with optimal effect from a four week treatment period.

Animals↗

PubMed1996

Determination of delta 9-tetrahydrocannabinol levels in brain tissue using high-performance liquid chromatography with electrochemical detection.

delta 9-Tetrahydrocannabinol (delta 9-THC) is the major psychoactive component of cannabis. To assist in investigating the mechanism(s) of action of delta 9-THC, a convenient method for determining its levels in brain tissue is required. We now describe a method for determining nanogram quantities of delta 9-THC in rat brain tissue. The method employs solvent extraction with methanol-hexane-ethyl acetate, followed by analysis using liquid chromatography with electrochemical detection. Overall recoveries were greater than 80%. The relationship between the peak-height ratio for processed standards extracted in the presence of tissue (delta 9-THC/internal standard) and the amount of delta 9-THC added was shown to be linear within the range of concentrations examined. Quantitative measurements of delta 9-THC in different brain regions following the intravenous administration of delta 9-THC are presented as examples of the applications of this method.

Animals↗

PubMed1996

The in vivo quantification of myocardial performance in rabbits: a model for evaluation of cardiac gene therapy.

Evaluating cardiac gene therapy in the intact animal requires an index of cardiac function capable of detecting regional differences in contractility in a load-independent fashion. Potentially load-insensitive measures of ventricular performance were therefore evaluated in 10 open- and closed-chested, anesthetized rabbits. LV transmural pressure and myocardial segment length were measured using micromanometry and sonomicrometry during steady-state and transient inferior vena caval occlusion, over a range of inotropic and loading conditions. For each intervention, segmental stroke work was calculated as the area within the left ventricular transmural pressure-length loops at a given end-diastolic segment length during inferior vena caval occlusion; regression analysis was applied to obtain the linear Frank-Starling relationship. In both open- and closed-chested states, these relationships were highly linear (r = 0.97 +/- 0.1) and reproducible. The slope of the linear relationship between segmental stroke work and end-diastolic segment length increased significantly with calcium and epinephrine infusions (P < 0.05 v control) but was not significantly altered by decreased afterload or increased afterload (P > 0.4). The x-intercept was not significantly altered by changes in intropy or afterload (P > 0.4). These data validate the linear Frank-Starling relationship and the slope, MW, as a load-insensitive index of contractility in the intact rabbit. This study presents a novel approach to the quantification of regional cardiac function in smaller animals.

Animals↗

PubMed1996

Prophylaxis against Staphylococcus epidermidis vascular graft infection with rifampicin-soaked, gelatin-sealed Dacron.

An animal model was used to assess the efficacy of rifampicin-impregnated, gelatin-sealed Dacron in the prevention of vascular graft infections caused by Staphylococcus epidermidis. Under a general anaesthetic an interposition graft was placed into sheep carotid artery. On completion of the operation 1 ml of normal saline containing 10(8) colony forming units (cfu) of a slime-producing S. epidermidis was inoculated directly onto the graft. After 3 weeks the graft was harvested. Swabs were taken of perigraft tissues, and of external and internal aspects of the graft. A 3-5-mm segment of the graft was incubated in broth medium and a second segment was ground for 5 min and incubated in broth medium. The presence of abscess formation and anastomotic disruption was assessed. Ten sheep received a gelatin-sealed Dacron graft (control), while nine received the same graft impregnated with rifampicin at a concentration of 1.2 mg/ml (treated). Eight of 10 control grafts were infected, with 30 of 50 possible cultures positive, compared with four of nine treatment grafts infected (P = 0.13) and 13 of 45 cultures positive (P = 0.004). The control group had four abscesses and two anastomotic disruptions; the treatment group had no abscesses (P = 0.05) or anastomotic disruptions (P = 0.26). Other organisms were isolated from nine of the 12 infected grafts, most commonly Staphylococcus aureus. There was no development of resistance to rifampicin. Rifampicin-impregnated, gelatin-sealed Dacron is successful at reducing the incidence of S. epidermidis vascular graft infection.

Administration, Topical↗

PubMed1995

Cobalt-permeable non-NMDA receptors in developing chick brainstem auditory nuclei.

Kainate, an agonist at non-NMDA glutamate receptors, evoked strong concentration-dependent cobalt accumulation in the chick brain stem auditory nuclei angularis, laminaris (NL) and magnocellularis (NM). This effect could be blocked completely by the AMPA/kainate receptor antagonist CNQX and the AMPA antagonist GYKI 53655 but not by antagonists of NMDA receptors or voltage-sensitive calcium channels. Kainate (30 microM) evoked cobalt uptake from embryonic day (E)9 through E21, with a peak intensity at E15. Before E13, uptake occurred mainly in NL but declined markedly in NM after E15 and ceased in NL by E21. We conclude that calcium-permeable non-NMDA receptors are transiently expressed at the time when mature neuronal number, form and synaptic connectivity are established.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1995

The role of GABAA receptors in the subsensitivity of Purkinje neurons to GABA in genetic epilepsy prone rats.

The GABA receptor subtype mediating responses of cerebellar Purkinje neurons to the neurotransmitter was evaluated and compared in GEPR-9 vs. nonepileptic, genetic control GEPR-NE rats. Quantitative analysis of responses to microiontophoretically applied GABA, muscimol and baclofen indicated that the inhibitory action of GABA on cerebellar Purkinje neurons was mediated by GABAA receptors since muscimol produced responses similar to those of GABA and baclofen was without substantial electrophysiological action. In addition, Purkinje neurons in GEPR-9 animals showed a similar reduced sensitivity to both GABA and muscimol. Radioligand binding studies using the GABAA receptor selective ligand, [3H]muscimol, and the benzodiazepine receptor selective ligand, [3H]flunitrazepam, were conducted on cerebellar and cortical homogenates from GEPR 9, GEPR-NE and Sprague-Dawley rats. No differences in the Kd or Bmax for these ligands among the three groups studied were observed. The lack of significant changes in the Kd and Bmax for these two ligands in the cerebellum suggests that the mechanism for the observed subsensitivity to GABA in the GEPR 9 rat lies beyond the level of the receptor, perhaps at the signal transduction process for GABA mediated inhibitory responses.

Animals↗

PubMed1995

Overexpression of NGF within the heart of transgenic mice causes hyperinnervation, cardiac enlargement, and hyperplasia of ectopic cells.

Nerve growth factor (NGF) supports the survival of developing sympathetic and a subpopulation of sensory neurons. In the adult it participates in maintenance of the neurotransmitter phenotype of responsive neurons. The amount of NGF synthesized by a given target tissue determines its final innervation density; those developing neurons that fail to receive sufficient NGF undergo apoptosis. In order to examine the ramifications of this principle in the context of a specific target organ, a transgenic mouse model was developed in which NGF expression was increased in developing and adult cardiac tissue by placing a NGF minigene under the transcriptional control of the cardiac-specific alpha-myosin heavy chain promoter. Transgenic mice developed cardiac enlargement secondary to both an increase in myocardial mass and the presence of an abundant ectopic cell population. Immunohistochemical analyses with the neural marker S-100 revealed staining of a subpopulation of ectopic cells, suggesting their derivation from the neural crest. Whereas immunostaining for the neuronal-specific protein neuron-specific enolase demonstrated labeling of another subpopulation of ectopic cells within the heart. Measurements of cardiac tissue catecholamine levels revealed a marked elevation in transgenic mice, consistent with sympathetic hyperinnervation. Analysis of mediastinal sympathetic ganglia revealed increases in both the size and the number of neurons. In this model, increased expression of NGF produced hyperinnervation of the heart, pathological cardiac growth, and the recruitment and/or expansion of an ectopic, neural crest-derived cell type.

Animals↗

PubMed1995

Sustained hypertension in Dahl rats. Negative correlation of agonist response to blood pressure.

The perfused mesenteric vasculature of Dahl salt-sensitive rats on a high salt diet for 5 days (prehypertensive or early hypertensive) is selectively supersensitive to norepinephrine. The present goal was to determine whether that supersensitivity was maintained as hypertension developed. Littermates of salt-sensitive and salt-resistant rats (Dahl Brookhaven strain) were followed on low or high salt for up to 6 weeks. Systolic blood pressure was elevated in the salt-sensitive, high salt rats after 3 or 6 weeks but not after 5 days of the diet. The perfused mesenteric vascular beds from salt-sensitive rats were supersensitive to norepinephrine and nerve stimulation but not to potassium chloride when the rats had been maintained for 5 days or 3 weeks on the high salt diet. However, responses to norepinephrine declined after 6 weeks of the high salt diet. To determine whether sustained high blood pressure has a negative effect on mesenteric vascular responses, we conducted additional experiments with perfused mesenteric vascular beds from salt-sensitive Brookhaven (high salt, 5 weeks) and Rapp (high salt, 6 weeks) animals. Both groups exhibited significant negative correlations between in vivo systolic pressure and maximal responses of mesenteric vessels to norepinephrine and potassium chloride. We suggest that sustained hypertension in Dahl rats has a negative effect on the contractility of the mesenteric arterial system that, by 5 to 6 weeks, masks the initial supersensitivity to norepinephrine. No effects of any diet on the dilating responses of the mesenteric vessels to acetylcholine were observed in any group.

Animals↗

PubMed1995

Adaptive supersensitivity and the Na+/K+ pump in the guinea pig vas deferens: time course of the decline in the alpha 2 subunit.

Adaptive supersensitivity in the guinea pig vas deferens has been shown previously to be associated with decreases in transmembrane potential, Na+/K+-ATPase activity, [3H]ouabain binding sites, and density of the alpha 2 subunit of the pump. One of several procedures that induce adaptive supersensitivity in the guinea pig vas deferens is neurotransmitter depletion by chronic administration of reserpine. Guinea pigs were treated with reserpine (1.0 mg/kg/day, intraperitoneally) for 2, 5, or 8 days. Tissues were homogenized and the concentration of the alpha 2 subunit was quantified by use of the selective antibody McB2, slot blot analysis, enhanced chemiluminescence, and densitometric analysis. As reported previously, the concentration of the alpha 2 protein was reduced 41% after 5 days of pretreatment. The reduction was maintained at 8 days (37%). However, there was no change from control after 2 days of pretreatment with reserpine. Thus, the time course of the decline in the alpha 2 subunit is similar to that of the appearance of supersensitivity, depolarization, and the declines in Na+/K+-ATPase and [3H]ouabain binding established earlier. Based upon results in the literature for several different tissues and species, membrane depolarization and decreases in Na+/K+ pump sites may represent widely occurring adaptive mechanisms.

Adaptation, Physiological↗