bluuebunny/crossref_metadata_2025 huggingface dataset:
Deuterium oxide reduces agonist and depoiarization-induced contraction of rat aortic rings
Authors: McWilliam T. M. , Liepins A. , Rankin A. J.
Published: April 2011

The influence of deuterium oxide (D2O) on calcium-dependent vascular smooth muscle contraction was investigated. The effect of D2O on receptor-operated calcium channels was investigated with phenylephrine-induced contraction in the rat aortic ring preparation. D2O depressed the contraction response in a dose-dependent manner with 50% inhibition of maximum contraction observed with 60% D2O. The effect of 60% D2O on phenylephrine-induced contraction was reversible and not dependent on an intact endothelium. Sixty percent D2O also reduced potassium chloride induced contractions by 50%, indicating an effect on voltage-operated calcium channels. Studies with Bay K 8644, and L-type calcium channel activator, confirm an effect on utilization of extracellular calcium sources and on the voltage-operated calcium channel. Sixty percent D2O also depressed a calcium contraction dose–response curve by approximately 25%. Likewise, a change in the pD2′ for nifedipine in the presence of D2O may indicate an effect on the nifedipine binding site and (or) the voltage-dependent calcium channel. Further studies were performed to determine whether the D2O effects were nonspecific or selective effects on the receptor- and voltage-operated calcium channels. Sucrose-induced contaction in the presence of 60% D2O was found to be inhibited by approximately 50%. D2O similarly affected isoprenaline relaxation, which would suggest a nonspecific D2O effect on the vascular smooth muscle contractile process.Key words: deuterium oxide, vascular smooth muscle, calcium channels, rat aorta.
Chronic hydralazine treatment alters the acute pressure–natriuresis curve in young spontaneously hypertensive rats
Authors: Kline Robert L. , McLennan Graham P.
Published: April 2011

The pressure–natriuresis relationship was studied in anesthetized, 7- to 9-week-old control spontaneously hypertensive rats (SHR) and in SHR that had been treated with hydralazine (20 mg∙kg−1∙day−1 in drinking water) starting at 4–5 weeks of age. To minimize reflex changes in kidney function during changes in renal artery pressure, neural and hormonal influences on the kidney were fixed by surgical renal denervation, adrenalectomy, and infusion of a hormone cocktail (330 μL∙kg−1∙min−1) containing high levels of aldosterone, arginine vasopressin, hydrocortisone, and norepinephrine dissolved in 0.9% NaCl containing 1% albumin. Changes in renal function were measured using standard clearance techniques, while renal artery pressure was varied between 136 ± 1 and 186 ± 2 mmHg (1 mmHg = 133.32 Pa) in control SHR (n = 10) and between 113 ± 1 and 162 ± 2 mmHg in treated SHR (n = 11). Mean arterial pressure (+SE) under Inactin anesthesia was 172 ± 3 mmHg in control SHR and 146 ± 3 mmHg in treated SHR (p < 0.05). Where renal artery pressure overlapped between groups, there were no significant differences in glomerular filtration rate. Renal blood flow was also similar in both groups, although at 160 mmHg blood flow was slightly but significantly reduced in treated SHR. Urine flow and total and fractional sodium excretion increased similarly with increases in renal artery pressure in both groups, but the pressure–natriuresis curve in hydralazine-treated SHR was displaced to the left along the pressure axis. The data indicate that chronic administration of hydralazine in young SHR enhances fractional sodium excretion, suggesting that tubular reabsorption of sodium is decreased by hydralazine.Key words: renal function, volume loading, sodium excretion.
Contraction of reptile, amphibian, and fish blood vessels by endothelin-1
Authors: Poder Thomas C. , Silberberg Shai D. , Rampe David
Published: April 2011

Endothelin-1, a 21 aminio acid peptide originally isolated from porcine endothelial cells, has been reported to contract arteries and veins from several mammalian species. We studied the effect of endothelin-1 on blood vessels removed from turtle (Pseudymes scripta), frog (Rana pipiens), and catfish (Amiurus melas). The vessels were suspended for isometric recording in thermally controlled organ baths and were exposed cumulatively to endothelin-1 (0.5–100 nM). All vessels showed a concentration-dependent increase in isometric force. The half-maximal concentrations (EC50) of endothelin-1 were all in the nanomolar range: turtle left systemic arch (17.9 ± 1.2 nM), frog systemic arch (5.5 ± 1.1 nM), catfish mesenteric artery (6.3 ± 1.3 nM), and catfish posterior cardinal vein (2.5 ± 1.4 nM). Vessels from frog and catfish developed more tension when exposed to 100 nM endomelin-1 than to 80 mM KCl (ET/KCl tension ratio). Our observations that endothelin-1 potently contracts blood vessels from reptiles, amphibians, and fish suggest that endothelin-1 may be a vertebrate peptide mat has been conserved during evolution.Key words: endothelium-derived contracting factor, vascular smooth muscle, vasoactive peptide.
Endothelin-1 release from lamb ductus arteriosus; relevance to postnatal closure of the vessel
Authors: Coceani Flavio , Kelsey Lois
Published: April 2011

Our previous investigations have shown that endothelin-1 (ET-1) is a singularly potent constrictor of the ductus arteriosus and that a cytochrome P-450 system located in the sarcolemma is crucial for the contractile response of the vessel to oxygen. We have now studied the release of ET-1 from isolated ductus arteriosus preparations of near-term fetal lambs. Preparations produced measurable amounts of ET-1 under basal conditions (about 0.04 pg/100 mg wet weight∙min) both in the presence and absence of the endothelium. Anisomycin (10−4 M) reduced this release by 50%, while thrombin (1 U/mL) doubled the release. Treatment with a CO mixture (CO/O2 ratio, 0.27) inhibited ET-1 release from intact and endothelium-denuded preparations. We propose that oxygen triggers closure of the ductus arteriosus at birth by causing a conformational change in a specific cytochrome P-450, which, in turn, provides the signal for the synthesis of the constrictor ET-1.Key words: ductus arteriosus closure, oxygen, cytochrome P-450, endothelin.
Fatigue of mammalian skeletal muscle in situ during repetitive contractions
Authors: Stainsby W. N. , Brechue W. F. , Ameredes B. T. , O'Drobinak D. M.
Published: April 2011

When the gastrocnemius–plantaris muscle group of the dog is stimulated to contract repetitively for 30 min at frequencies high enough to generate [Formula: see text] levels at or near [Formula: see text] max, [Formula: see text] and mechanical performance decline with time. This decline with time is fatigue, and it occurs during twitch and tetanic contractions that are isometric or isotonic. There is oxidation of the mitochondrial electron transport system, and net lactic acid output is transient, ending after 20 min of contractions. Energy and substrate stores and intracellular pH are only moderately changed and do not appear to be well correlated with the development of fatigue. Blood flow through the muscle is well correlated with the development of fatigue and decreases as fatigue develops in a manner that keeps the blood arteriovenous O2 difference nearly constant. Changing the blood flow alters the rate of development of fatigue as an inverse relation, and this response does not appear to be related to changes in the availability of O2 in the mitochondria. Nerve–muscle transmission of excitation does not seem to be involved in the development of fatigue. Excitation–contraction coupling is well accepted to be at least part of the genesis of the development of fatigue. Metabolic limitations and control may affect excitation–contraction coupling by one or more changes in the internal environment. Blood flow affects this system by an unknown mechanism. The role of blood flow in fatigue deserves further consideration.Key words: muscle fatigue, muscle blood flow, muscle [Formula: see text], genesis of fatigue in muscle.
The roles of ion fluxes in skeletal muscle fatigue
Authors: Lindinger Michael I. , Heigenhauser George J. F.
Published: April 2011

Intense muscle contractions result in large changes in the intracellular concentrations of electrolytes. The purpose of this study was to examine the contributions of changes in intracellular strong ions to calculated changes in steady-state membrane potential (Em) and muscle intracellular H+ concentration ([H+]i). A physicochemical model is used to examine the origin of the changes in [H+]i during intense muscle contraction. The study used the isolated perfused rat hindlimb intermittently stimulated to contract at high intensity for 5 min. This resulted in significant K+ depletion of both slow (soleus) and fast (white gastrocnemius, WG) muscle fibers and a release of K+ and lactate (Lac−) into venous perfusate. The major contributor to a 12- to 14-mV depolarization of Em in soleus and WG was the decrease in intracellular K+ concentration ([K+]i). The major independent contributors to [H+]i are changes in the concentrations of strong and weak ions and in CO2. Significant decreases in the strong ion difference ([SID]i) in both soleus and WG contributed substantially to the increase in [H+]i during stimulation. In WG the model showed that the decrease in [SID]i accounted for 35% of the increase in [H+]i (133–312 nequiv/L; pHi = 6.88–6.51) at the end of stimulation. Of the main contributors to decreased [SID]i increased [Lac−]i and decreased [K+]i contributed 40 and 60%, respectively, to increased [H+]i whereas a decrease in [PCr2−]i contributed to reduced [H+]i. It is concluded that decreased muscle [K+], during intense contractions is the single most important contributor to reduced Em and increased [H+]i. Depletion of PCr2− simultaneous to the changes in [Lac−]i and [K+]i prevents larger increases in [H+]i and helps maintain the intracellular acid–base state.Key words: exercise, acid–base, membrane potential, potassium, lactate.
β-Blockade and oxygen delivery to muscle during exercise
Authors: Hughson Richard L. , Kowalchuk John M.
Published: April 2011

The most commonly observed effect of β-blockade on cardiovascular function has been a reduction in heart rate both at rest and during exercise. The body attempts to compensate by increasing stroke volume and (or) increasing the extraction of O2 from the blood to maintain O2 delivery to the muscle. This paper examines the roles of muscle mass involved in the exercise as well as the time course of change in cardiac output and peripheral blood flow in an attempt to understand whether O2 supply is limited by β-blockade. Experiments are reported in which the kinetics of cardiac output response at the onset of submaximal cycle exercise were slowed in subjects taking oral propranolol. Taken in consideration with other data from our laboratory and with data in the literature, it was concluded that β-blockade does impair O2 transport. The degree of impairment is dependent on the total muscle mass involved and the metabolic demand.Key words: blood flow, cardiac output, fatigue, propranolol, oxygen uptake.
Conference summary: Diet as an environmental factor in development of insulin-dependent diabetes mellitus
Authors: Scott Fraser W. , Marliss Errol B.
Published: April 2011

An international symposium on diet as an environmental factor in development of insulin-dependent diabetes mellitus (IDDM) was held in Ottawa, Ont., Canada, September 1989. Several environmental factors such as viruses and chemicals, as well as diet modifications per se, were reviewed in both human and animal diabetes. Although the pathophysiology in the BB rat and nonobese diabetic (NOD) mouse may have different immunological mechanisms, both these animal syndromes of spontaneous IDDM are markedly affected by diet. In them, cereal-based rodent diets are the most diabetogenic and hydrolyzed casein-based purified diets are least diabetogenic. In two different NOD mouse colonies, diabetogenicity of cereal-based diets can be markedly decreased by extracting the diet with chloroform–methanol or water, reflecting either the different composition of the diets used in each colony or the chemical extraction and (or) alteration of certain diabetogenic agents. Thus, dietary lipids can be potent immune system modulators in several systems and the role of chloroform–methanol soluble agents in initiation and (or) promotion of the disease process is being studied. Attention was focused on protein sources previously identified by some groups as diabetogenic such as skim milk powder and wheat products, both of which can be found in natural ingredient rodent feeds. Circulating antibodies to dietary antigens such as bovine serum albumin and (crude) wheat gliadin may be elevated in diabetes-prone rodents and newly diagnosed patients, but their relationship to the pathogenesis of IDDM remains to be established. Because diet components can clearly influence the expression of the diabetic syndromes in the BB rat and NOD mouse, it will be crucial to identify the chemical nature of such components as a first step in understanding their mode of action. The epidemiological evidence for a role of diet in human IDDM was reviewed and is sufficient to suggest an association, but more data are required and such studies are currently underway. The complexity of the search for diabetogens in various diet constituents may be compounded by possible interaction with infectious agents and the large amounts of material required for testing in whole animal feeding experiments. It was the aim of this conference to examine the diet–IDDM relationship from a variety of perspectives that may ultimately contribute in different ways to identification of diabetogenic agents in our diet and possibly a safe and inexpensive means of avoiding or substantially delaying development of clinical IDDM in susceptible individuals.Key words: diabetes, pathogenesis, diet, nutrition, prevention.
Influence of physical activity and dietary restraint on resting energy expenditure in young nonobese females
Authors: Poehlman Eric T. , Viers Helen F. , Detzer Mark
Published: April 2011

An understanding of the physiological and behavioral determinants of resting energy requirements is important to nutritional considerations in females. We examined the influence of endurance training and self-reported dietary restraint on resting metabolic rate and fasting plasma hormones in 44 nonobese females characterized for body composition, maximal aerobic power [Formula: see text], and daily energy intake. To examine the association of metabolic rate and dietary restraint with hormonal status, fasting plasma levels of insulin, glucose, and thyroid hormones (total and free fractions of thyroxine and triiodothyronine) were determined. In univariate analysis, resting metabolic rate (kcal∙min−1) was positively related to [Formula: see text] (L∙min−1) (r = 0.54; p < 0.01). This relationship, however, was partially dependent on body size, since fat-free mass was also related to resting metabolic rate (r = 0.42; p < 0.01) and [Formula: see text] (L∙min−1) (r = 0.75; p < 0.01). After controlling for fat-free weight using partial correlation analysis, the relation between RMR and [Formula: see text] was weaker but still significant (partial r = 0.38; p < 0.05). On the other hand, high levels of dietary restraint were associated with higher levels of body fat (r = 0.31; p < 0.05) and a lower resting metabolic rate (r = −0.29; p = 0.07). These associations persisted after control for differences in fat-free mass. Total energy intake as well as total and free levels of triiodothyronine were not related to resting metabolic rate or level of dietary restraint. Our results suggest that the level of endurance training (i.e., [Formula: see text]) and dietary restraint, independent of differences in fat-free mass, contribute to individual variation in resting metabolic rate of nonobese females. These findings appear to be unrelated to fasting plasma concentrations of thyroid hormones. Whereas high levels of endurance training are associated with increased energy requirements at rest, higher levels of dietary restraint are associated with a lower resting metabolic rate and possibly a propensity to gain body fat.Key words: endurance training, dietary restraint, resting metabolic rate, females, energy intake.
Differences in distensibility between the anterior and posterior walls of the left ventricle in dogs
Authors: Zhou Zhao-Nian , Dong Sheng-Jing , Smith Eldon R. , Tyberg John V.
Published: April 2011

Nonuniformity of myocardial systolic and diastolic performance in the normal left ventricle has been recognized by a number of investigators. Lack of homogeneity in diastolic properties might be caused by or related to differences in the distensibility of different regions of the left ventricular (LV) wall. Thus, we compared the end-diastolic transmural pressure–strain relations in both the anterior and posterior LV walls in seven anesthetized dogs during two interventions (pulmonary artery constriction and aortic constriction). Transmural pressure was defined as the difference between LV intracavitary pressure and local pericardial pressure. LV pressure was measured using a micromanometer; pericardial pressures over the LV anterior and posterior wails were measured with balloon transducers. Circumferentially oriented pairs of sonomicrometer crystals were implanted in the midwall of the anterior and posterior walls of the LV to measure segment lengths. Strains were calculated as (L – L0)/L0, where L was the instantaneous segment length and L0 was the segment length when transmural pressure was zero. The pattern of end-diastolic transmural pressure–strain relations was similar in ail dogs. The change in strain in the posterior wall was always greater than that in the anterior wall. Opening the pericardium did not affect the difference in distensibility of the anterior and posterior walls. The results suggest that the posterior wall is more compliant than the anterior wall (that is, for a given difference in transmural pressure, the local segment length change of the posterior wall was greater). This seems consistent with other observations, which suggest that the posterior wall might make a greater contribution to diastolic filling.Key words: regional ventricular function, diastolic suction, elastic properties.
Cardiac function of the diabetic renovascular hypertensive rat: effects of insulin and thyroid hormone treatment
Authors: Rodgers Robert L. , Davidoff Amy J. , Mariani Mark J.
Published: April 2011

The influences of hypertension and hypothyroidism on diabetic cardiomyopathy are not clear. We studied this problem further by characterizing the effects of chronic triiodothyronine (T3) treatment on cardiac performance of diabetic renovascular hypertensive (RVH) rats. Hypertension was effected by clipping the left renal artery of Wistar–Kyoto (WKY) rats, and diabetes was induced 2 weeks later by streptozotocin (STZ; 55 mg/kg i.v.). The WKY strain was selected because it is relatively resistant to the cardiodepressant effects of diabetes, so that the influence of superimposed hypertension would be more apparent. Performance of working Krebs–Henseleit buffer perfused hearts was quantified by measuring left ventricular pressure and flow characteristics. The results showed that renovascular clipping caused a marked hypertension and left ventricular hypertrophy (LVH) but had no effect on perfused heart performance after 10 weeks. They also showed that diabetes during the final 8 weeks (i) caused a marked impairment in the performance of perfused hearts ex vivo of hypertensive rats but had no measurable effect in the normotensive WKY, (ii) had no effect on arterial pressure of either the normotensive or the hypertensive rats but reduced heart rate of hypertensive animals in vivo, and (iii) caused equivalent hyperglycemia, hypoinsulinemia, and hypothyroidism (depressed serum T3 and T4 levels) of hypertensive and normotensive rats. Treatment of diabetic RVH rats with T3 (10 μg∙kg−1∙day−1) in vivo was nearly as effective as insulin therapy (10 U∙kg−1∙day−1) in preventing the cardiac dysfunction ex vivo and was as effective as insulin therapy in preventing the bradycardia in vivo and the decline in serum T3 levels, even though it intensified the hyperglycemia and body weight loss. The results provide support for a synergistic effect of diabetes and hypertension on heart function. They also add support to the hypothesis that attendant hypothyroidism contributes significantly to diabetic cardiomyopathy in the hypertensive rat.Key words: heart performance, triiodothyronine, hypothyroidism, cardiomyopathy.
The interaction of 3,5-pyrazolidinedione drugs with receptors for f-Met-Leu-Phe on human neutrophil leukocytes: a study of the structure–activity relationship
Authors: Levesque Luc , C.-Gaudreault René , Marceau François
Published: April 2011

The 3,5-pyrazolidinedione (3,5-P) drugs, phenylbutazone and sulfinpyrazone, have been reported to bind to receptors for the chemotactic peptide, f-Met-Leu-Phe, and to behave as functional antagonists of f-Met-Leu-Phe in human and rabbit neutrophils. To explore the structure–activity relationship of this family of drugs for f-Met-Leu-Phe receptor binding, 36 drugs with the 3,5-P structure, a structure related to antipyrine, or an unrelated structure were tested as competitors for the binding of f-Met-Leu-Phe-Lys-fluorescein isothiocyanate on human neutrophils by flow cytometric analysis. Only drugs possessing the 3,5-P ring were significant competitors. The five most potent 3,5-Ps behaved as selective antagonists of f-Met-Leu-Phe-induced superoxide anion release by neutrophils. The potency was not correlated to the pKa or to their capacity to inhibit prostaglandin E2 released from culture fibroblasts but instead appeared to be correlated to their apparent octanol–buffer partition coefficients. The most potent f-Met-Leu-Phe antagonist identified, 1,2-diphenyl-4-(3-(1-naphthyl)propyl)-3,5-pyrazolidinedione (DPN), may also possess an improved pharmacodynamic specificity compared with phenylbutazone and sulfinpyrazone, as it was less potent than phenylbutazone in the inhibition of prostaglandin synthesis and it was not cytotoxic. DPN may be a prototype for a valuable new class of anti-inflammatory drugs.Key words: human neutrophils, 3,5-pyrazolidinediones, phenylbutazone, sulfinpyrazone, f-Met-Leu-Phe, chemotactic peptide antagonists.
Failure of chronic hyperinsulinemia to suppress pancreatic glucagon in vivo in the rat
Authors: Brubaker Patricia L. , Kazumi Tsutomu , Hirano Tsutomu , Vranic Mladen , Steiner George
Published: April 2011

To determine the effects of chronic hyperinsulinemia on glucagon release, rats were made hyperinsulinemic for 14 days by supplementation of drinking water with sucrose (10%; sucrose-fed) to increase endogenous release or by implantation of osmotic minipumps (subcutaneous, s.c; or intraperitoneal, i.p.) to deliver exogenous insulin (6 U/day). Both s.c. and i.p. rats also had sucrose in the drinking water to prevent hypoglycemia. Plasma insulin levels were significantly elevated in sucrose-fed, s.c, and i.p. rats. However, glucose levels were significantly elevated in sucrose-fed rats only. Surprisingly, plasma glucagon concentrations were elevated in i.p. and s.c. rats and were not suppressed in sucrose-fed rats. Inverse relationships were found between the plasma levels of insulin and glucose (n = 65; r = −0.42, p < 0.0001) and between glucose and glucagon (n = 73; r = −0.46, p < 0.0001). However, unexpectedly, a positive correlation between insulin and glucagon (n = 65; r = 0.47, p < 0.0001) was established. As suppression of plasma glucagon levels below basal was not observed in any of the hyperinsulinemic or hyperglycemic rats, we wished to establish further whether pancreatic glucagon release could be suppressed below basal levels in the rat by another means. Thus, high doses of somatostatin (50–100 μg∙kg−1∙min−1) were infused for 45 min into normal rats without or with a concomitant hyperinsulinemic, hyperglycemic glucose clamp. Somatostatin fully suppressed insulin, but although plasma glucagon levels were decreasd by somatostatin infusion relative to saline-infused animals, there was still no suppression below basal levels. Thus, the rat A cells are less sensitive to somatostatin than are those of other species. The results of this study demonstrate that chronic endogenous or exogenous hyperinsulinemia does not inhibit glucagon secretion, even in the presence of hyperglycemia. Factors other than insulin may therefore play an important role in the regulation of the pancreatic A cell in the chronic hyperinsulinemic rat.Key words: glycemia, insulin, glucagon, somatostatin, very low density lipoprotein.
Mechanisms of pain arising from articular tissues
Authors: Sessle Barry J. , Hu James W.
Published: April 2011

This paper reviews the peripheral and central neural mechanisms underlying pain from articular tissues innervated by spinal and trigeminal afferents. The paper especially addresses trigeminal mechanisms related to pain from the temporomandibular joint and its associated craniofacial musculature. Recent studies have shown the existence of articular nociceptive primary afferents that project to the spinal cord dorsal horn and trigeminal brainstem complex. A particular feature of most neurones receiving these deep nociceptive afferent inputs is their responsivity also to cutaneous nociceptive afferent inputs. This suggests the involvement of these neurones not only in the detection of acute articular pain, but also in the hyperalgesia and poor localization, spread, and referral of pain that characterize many painful conditions of joints and other deep structures. While only limited information is available on related higher brain centre mechanisms, convergence and interaction between cutaneous and deep afferent inputs also seem to be a characteristic of somatosensory neurones in the thalamus and somatosensory cerebral cortex. Muscle and autonomic reflexes may be induced by such deep noxious stimuli, but the functional significance of some of these effects (e.g., in relation to clinical concepts of myofascial dysfunction) requires further study in more appropriate functional settings.Key words: pain, articular tissues, algesic, afferents, neurones.
Central neurophysiological processing of joint pain on the basis of studies performed in normal animals and in models of experimental arthritis
Authors: Guilbaud Gisèle
Published: April 2011

On the basis of anatomical and electrophysiological studies, this review summarizes first, the data dealing with the transmission of joint inputs in the central nervous system of normal animals at the spinal and supraspinal levels. It appears that in these conditions neuronal responses to mechanical noxious stimuli of the joints are relatively few and (or) weak. Second, in sharp contrast, the studies performed in polyarthritic rats have emphasized the profound changes in the activities (spontaneous firing and responsiveness) of the somatosensory neurones at various levels of the central nervous system (CNS), including the thalamus and primary somatosensory cortex; many were spontaneously active and a majority of them could be maximally activated by gentle mechanical stimuli applied to the inflamed joints. Although the change in the sensitivity of the peripheral mechanoreceptors has a major role in the modifications described in the CNS, additional observations have suggested a complex interaction between peripheral and central processes. On the basis of the recent data obtained in poly- and mono-arthritic animals, the following phenomena have been successively considered: the segmental and hetero-segmental "cross-talk" and their possible relationship with referred pain; the involvement of "new" neuronal populations as a possible basis of a selective system for joint pain; and the possible involvement of changes in the various control systems that normally modulate the nociceptive inputs at different levels of the CNS.Key words: joint pain, electrophysiology, somatosensory system, thalamus, rat.
Illness behavior and dysfunction: review of concepts and application to chronic pain
Authors: Dworkin Samuel F.
Published: April 2011

The purpose of this presentation is to review the elements that comprise the concept of illness behavior including elaboration of a more formal theoretical and operational model for illness behavior and then discuss the application of the illness behavior model to chronic pain, especially chronic orofacial pain. The model of illness behavior presented emphasizes four critical areas of conceptual interest, namely, (1) monitoring of somatic signals; (2) cognitive processes whereby bodily symptoms are interpreted; (3) attaching meaning to symptoms in the context of emotional state and concurrent environmental events; and (4) the ethnocultural influences that pervade meaning and shape coping responses. Our model of illness behavior was generalized from a closely related model developed to guide research when the specific illness behavior of interest was dysfunctional chronic pain behavior. We also include a time dimension in our chronic pain model. Dysfunctional chronic pain is understood to be the most important undesirable consequence associated with suffering a persistent pain condition. Dysfunctional chronic pain is a subset of illness behaviors inconsistent with medically documented findings, while the complaints of pain are prominent. Changes occur in emotional status, most typically reported as mood and behavioral changes associated with depression, such as demoralization, helplessness, and social isolation. Excesses in medical care, hospitalizations for surgery, and abuse of medications are further characteristics of dysfunctional chronic pain.Key words: illness, behavior, chronic, pain, dysfunction.
Fibromyalgia–a clinical entity?
Authors: Henriksson Karl G. , Bengtsson Ann
Published: April 2011

Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain and tenderness at specified sites, fatigue, and unrefreshing sleep. The American College of Rheumatology (ACR) has recently accepted diagnostic criteria for FM. The ACR criteria have high diagnostic specificity, sensitivity, and accuracy. Laboratory investigations show a disturbed microcirculation in painful muscles, a decrease in adenosine triphosphate and phosphocreatine, and a reduced relaxation rate. Pain analyses indicate that the pain is nociceptive. A characteristic physiological sleep disturbance has been described that is correlated to the symptoms. The etiology of FM is not known. The etiology may be different in different patients. FM is a clinical entity, but should be regarded as a syndrome rather than a disease.Key words: pain, muscular pain, fibromyalgia, fibrositis.
Adrenoceptors of the human internal thoracic artery
Authors: Nakatsu K. , Pym J. , Witte S. , Marks G. S. , Brien J. F.
Published: April 2011

Adrenoceptor function in the human internal thoracic artery (ITA) was characterized in vitro using segments of the artery obtained during coronary bypass operations. Specimens were prepared as isolated arterial rings mounted in a tissue bath, and mechanical activity (isometric tension) was measured in response to drugs. The ITA responded to phenylephrine (PE), epinephrine, and norepinephrine with concentration-dependent contractions. The PE-induced contractions were antagonized by phenoxybenzamine, prazosin, and high concentrations of yohimbine. The ITA was not effectively contracted by clonidine in the concentration range normally associated with α2-adrenoceptor stimulation. The β-adrenoceptor agonist, isoproterenol, had a weak and variable effect on the ITA; samples from 9 out of 12 subjects did not respond to isoproterenol, whereas samples from 3 subjects responded with relaxations of between 33 and 42%. These in vitro studies indicate that the most important adrenoceptors of the human ITA are α-adrenoceptors; this may be relevant for the pharmacologic management of patients undergoing coronary bypass surgery using the ITA.Key words: human internal thoracic artery, α-adrenoceptors, β-adrenoceptors, phenylephrine, prazosin.
Characterization of sulfidopeptide leukotriene responses in sheep tracheal smooth muscle in vitro
Authors: Tomioka K. , Jackowski J. T. , Abraham W. M.
Published: April 2011

We have investigated the effects of leukotrienes (LTs) on isolated tracheal smooth muscle from sheep sensitive to Ascaris suum antigen. LTC4 and LTD4 produced dose-dependent contractions of sheep trachea, but LTE4 was virtually inactive. YM-17690, a non-analogous LT agonist, produced no contractile response up to 100 μM. Indomethacin (5 μM) had no effect on LTC4- and LTD4-induced contractions. L-Serine borate (45 mM), an inhibitor of γ-glutamyl transpeptidase, shifted the dose–response curve of LTC4 to the left by 161-fold, and L-cysteine (6 mM), an inhibitor of aminopeptidase, shifted the dose–response curves of LTC4 and LTD4 to the left by 67- and 23-fold, respectively. YM-16638 (1 μM), an LT antagonist, shifted the dose–response curves of LTC4 and LTD4 to the right with pKB values of 6.57 and 7.13, respectively. YM-16638 did not affect LTC4-induced contractions of L-serine borate-treated tissues, indicating that the compound acts only on LTD4 receptors in sheep trachea. LTE4 (1 μM) shifted the dose–response curves of LTC4 and LTD4 to the right with pKB values of 6.87 and 7.31, respectively. YM-17690 (10 μM) showed effects similar to LTE4, suggesting that the compound acts as an LTE4 agonist in sheep trachea. These results suggest that in sheep tracheal smooth muscle (a) LTC4 and LTD4 produce contractions, (b) these LT-induced contractions are not mediated by cyclooxygenase products, (c) LTC4 is converted to LTD4 and then to LTE4, and (d) the potency of the LTC4- and LTD4-induced contractions is increased when their conversion to LTE4 is inhibited. This potentiation may result from the inability of LTE4 to contract sheep trachea and (or) its antagonist actions.Key words: leukotriene antagonist, receptors, asthma.
Characterization of kinin binding sites: identity of B2 receptors in the epithelium and the smooth muscle of the guinea pig ileum
Authors: Tousignant C. , Guillemette G. , Barabé J. , Rhaleb N.-E. , Regoli D.
Published: April 2011

Binding of [125I-Tyr8]bradykinin (BK) was measured in homogenates of epithelial and smooth muscle layers of the guinea pig ileum. Binding assays were performed at 4 °C for 40 min (smooth muscle) or 90 min (epithelium) in 25 mM PIPES buffer at pH 6.8 in the presence of 1 mM 1,10-phenanthroline, 140 μg/mL bacitracin, 1 mM captopril, 1 mM dithiothreitol, and 0.1% bovine serum albumin. Specific binding of [125I-Tyr8]BK (0.32 nM) to epithelial and smooth muscle cell membranes was linearly related to protein concentration between 0.05 and 0.5 mg/mL. Equilibrium experiments showed that specific binding of [125I-Tyr8]BK was saturable and Scatchard analysis indicated the presence of a high affinity site with a Kd value of 1.6 nM and a Bmax. of 156 fmol/mg of protein in the epithelial cell membranes. In smooth muscle membranes, Kd was 1.8 nM and the maximum number of binding sites was 58 fmol/mg of protein. Unlabelled peptides, namely bradykinin, [Tyr8]BK, [Hyp3]BK, D-Arg[Hyp3]BK, [Hyp3,Tyr(Me8)]BK, and kallidin displaced [125I-Tyr8]BK binding while other peptides, angiotensin II and substance P, had no effect. A series of B2-receptor antagonists displaced [125I-Tyr8]BK from specific binding sites with IC50 values ranging from 16 to 152 nM on epithelial cell membranes; similar values were obtained from smooth muscle cell membranes. These findings suggest that the binding sites in both preparations are of the B2 type. B1-receptor agonists and antagonists were found to be inactive at concentrations up to 10−4 M. Results obtained in the two preparations were compared and a positive highly significant correlation was demonstrated between the two sets of data. It is therefore concluded that B2 receptors found in the epithelium and the smooth muscle membranes of the guinea pig ileum are identical. These sites are similar to the functional receptor mediating the myotropic effect of bradykinin in the ileum.Key words: kinins, epithelium, smooth muscle, guinea pig ileum, binding and biological assays.
Diabetes-induced rat hyposensitivity to compound 48/80
Authors: Casacó A. , Carvajal D. , Tolón Z.
Published: April 2011

Rat mortality and contractile responses of isolated tracheas to compound 48/80 from rats made diabetic 4 days before by a single intravenous injection of alloxan and from diabetic rats that had been treated with insulin 6 h before were compared with control animals. Diabetic animals and tracheal segments from diabetic rats were significantly less responsive to compound 48/80 than control and insulin-treated diabetic animals. On the other hand, diabetic animals have a lower quantity of peritoneal mast cells than control rats, and insulin restored the normal quantity of cells in diabetic animals. These data indicate that diabetes elicits an hyposensitivity to compound 48/80, possibly related to a diabetes-induced decrease in the mast cell count.Key words: diabetes mellitus, bronchial hyposensitivity, compound 48/80, mast cell.
Morphology and physiology of capillary systems in subregions of the subfornical organ and area postrema
Authors: Gross Paul M.
Published: April 2011

From recent morphological and physiological studies of capillaries, I shall review four new or revised concepts about blood–tissue communication in the subfornical organ (SFO) and area postrema (AP). First, the capillary systems of SFO and AP exhibit subregional differentiation correlated topographically with cytoarchitecture, densities of immunoreactivity for several peptides and amines, cellular sensitivity to neuroactive substances, afferent neural terminations, and tissue metabolic activity. Thus, contrary to frequent citations, the angioarchitecture and microcirculatory physiology of these small sensory nuclei are not homogeneous. Second, electron microscopic, morphometric, and topographical studies reveal that SFO contains three different types of capillary and AP has two. The differentiated capillary morphology appears to be well organized for specialized functions particularly in SFO subregions. No other body organ or small tissue region is known to have such capillary diversity, further highlighting the complex functions served by SFO. Third, pools of interstitial fluid (Virchow–Robin spaces) surrounding type I and III capillaries in SFO and AP may participate in the receptive properties of these organs as low-resistance pathways for rapid dispersion of blood-borne hormones inside their organ boundaries. The parenchymal walls of Virchow–Robin spaces appear to harbour metabolic mechanisms for hormones such as angiotensin II, and thus could vastly extend the effective blood–brain surface area of permeable capillaries in SFO and AP. Fourth, SFO and AP bear similar physiological characteristics of high blood volume, yet relatively low rates of blood flow. Accordingly, intracapillary blood velocity must be quite slow in these organs, and the duration of transit by blood and circulating messengers rather protracted. This feature of slow blood transit time likely compounds the sensory capability of SFO and AP, rendering increased contact time for blood-borne hormones to penetrate the permeable capillaries of these structures and interact with their known dense populations of receptors for several homeostatic substances involved in regulation of blood pressure and body fluids.Key words: morphometry, topography, cytoarchitecture, fenestrations, vesicles, blood flow, permeability, blood volume, transit time, pericapillary spaces.
Amino acids as transmitters of synaptic excitation in neocortical sensory processes
Authors: Hicks T. P. , Kaneko T. , Metherate R. , Oka J.-I. , Stark C. A.
Published: April 2011

Few synaptic transmitters are known to exist that are not represented in some region or another, or at some layer or other, in the cerebral cortex of mammalian brain. The more difficult job than mere identification of which substances are present, is that of the assignment of particular functional role(s) of such substances, and as well, of determining upon exactly which element(s) of the known synaptic circuitry of neocortex, such transmitters operate. Current wisdom subscribes to the view that the excitatory amino acids, most likely L-glutamate, and L-aspartate but perhaps also L-cysteate, L-homocysteate, L-cysteine sulfinate or even (although much less likely) the endogenous dipeptide substance, N-acetyl-L-aspartyl-L-glutamate, are the major excitatory synaptic transmitters of intracortical (associational) fibres, of corticofugal projections, and, as this article will attest, of thalamocortical inputs, as well. What particular limits, or restrictions, are imposed upon these generalizations, such as whether the data pertain only to primary sensory areas or follow some other yet to be determined rule, remains to be discovered in future experiments. This paper first presents an overview of the advances in understanding that have come about during the past few decades concerning the synaptic roles of amino acid transmitters. Next, an experimental section presents new evidence based on release studies and the microiontophoretic approach, which supports the view that the amino acids, glutamate and aspartate, interact with specific, pharmacologically identified subtypes of receptors in neocortex as transmitters of synaptic excitation released from thalamic afferent terminals.Key words: excitatory amino acids, cerebral cortex, synaptic transmitter, sensory systems.
Plasma epinephrine in chronically adrenodemedullated rats: lack of response to acute or chronic exercise
Authors: Jean Christine , Tancrède Gilles , Rousseau-Migneron Suzanne , Nadeau André
Published: April 2011

Even if it is well established that epinephrine is a hormone originating from the adrenal medullae, the reappearance of circulating epinephrine has been reported in rats a few days after adrenodemedullation. To verify if the extra-adrenal tissue responsible for this epinephrine production can be stimulated, sham-operated or adrenodemedullated rats, either trained or kept sedentary, were submitted to an acute exercise stimulation test. Blood sampling was done before and after the test in precannulated rats for the determination of plasma epinephrine, norepinephrine, and corticosterone levels. Basal epinephrine levels were significantly reduced in trained and sedentary adrenodemedullated rats compared with their sham-operated counterparts. In response to exercise, there was no significant rise in epinephrine levels in both groups of adrenodemedullated rats. The norepinephrine levels in the basal state and in response to exercise were not altered by adrenodemedullation nor by physical conditioning. Basal corticosterone levels were similar between adrenodemedullated and sham-operated animals, either trained or kept sedentary. In response to exercise, corticosterone levels increased significantly in each group of rats but to a lesser extent in both groups of adrenodemedullated animals. These data indicate that the extra-adrenal epinephrine secretion that develops in the absence of adrenal medullae is not influenced by acute exercise nor by physical training.Key words: adrenodemedullation, extra-adrenal epinephrine, rat, physical training, acute exercise.
Lung liquid production by in vitro lungs from fetal guinea pigs: studies with metabolic inhibitors
Authors: Perks A. M. , Ruiz T. , Vanderhorst E.
Published: April 2011

Lungs from fetal guinea pigs (62 ± 2 days of gestation) were supported in vitro for 3 h, and lung liquid production was measured by dye dilution. Eighteen untreated preparations produced fluid at 1.76 ± 0.30 mL∙kg−1 body weight∙h−1 during the first hour, with no significant changes in later hours. When inhibitors of respiratory processes were placed in the outer saline during the middle hour, production changed significantly, as follows: (a) sodium iodoacetate at 10−3 M stopped production (87.2 ± 10.3 and 100% reductions, successive hours; n = 6), at 10−4 M it reduced production (60.0 ± 10.3 and 63.4 ± 9.3% reduction, successive hours; n = 12); (b) sodium fluoride, 10−3 M, almost stopped production (93.2 ± 12.1 and 89.5 ± 9.3% reductions, successive hours; n = 6); (c) sodium cyanide at high concentration (10−3 M) reduced production slowly (35.5 ± 12.3 and 73.1 ± 22.4%, successive hours; n = 6); (d) sodium azide, 10−3 M, also reduced production (67.6 ± 14.2 and 59.7 ± 14.0%, successive hours; n = 6); total lactate lost rose 1.8 ± 0.5 fold; (e) dinitrophenol produced strong reabsorptions; at 10−3 M, production fell 115.4 ± 15.9 and 113.1 ± 47.3%, successive hours (n = 4), and at 2 × 10−4 M it fell 143.8 ± 33.8 and 153.4 ± 26.7%, successive hours (n = 6); total lactate lost rose 2- to 3-fold. Control preparations showed no significant changes. The results suggest that lung liquid production requires glycolysis and aerobic metabolism. However, reabsorption appears to continue on glycolysis alone, a particularly useful situation for neonates suffering respiratory distress.Key words: fetus, lung liquid, metabolic inhibitors.
Trypsin activation of inactive renin: plasma blanks and angiotensin I radioimmunoassay
Authors: Barrett Jack D. , Eggena Peter
Published: April 2011

Divergent conclusions exist as to whether inactive renin is present in nephrectomized rat plasma. A major factor contributing to this conflict may be related to significant changes in the "plasma blank" when trypsin-treated plasma is subjected to angiotensin I (AI) radioimmunoassay (RIA). In normal, but not nephrectomized rat plasma, AI-like substances are present in direct proportion to active renin. These substances are destroyed by trypsin. However, trypsin generates additional AI-like material, in both normal and nephrectomized rat plasma. This material, which is present in proportion to the renin substrate concentration, does not appear to be tetradecapeptide (TDP). In normal plasma, however, exogenous TDP is converted to AI in proportion to the active renin concentration and AI generation from TDP is increased by activation of inactive renin. However, in nephrectomized rat plasma, no AI generation from TDP was evident either before or after trypsin treatment. The coincident tryptic generation of a substance that quenches the levels of AI detected by RIA, combined with significant changes in the levels of endogenous and trypsin generated AI-like substances, may have significant bearing on the measured levels of inactive renin.Key words: prorenin, nephrectomy, angiotensin I radioimmunoassay, rat, plasma blanks.
Plasma active and inactive renin and fetal complications in women with high risk pregnancies
Authors: Ferraris Paola , Quorso Patrizia , Gazzano Gabriella , Cianci Massimo , Sala Carla , Turolo Lucia , Pulazzini Esmeralda , Morganti Alberto , Ambroso Giancarlo , Como Gabriella , Candiani Giambattista , Polvani Filippo
Published: April 2011

To examine whether the activation of the renin system, which occurs during pregnancy, may be relevant for the development and the outcome of the fetus, we measured active and inactive renin throughout gestation in 29 women having a pregnancy defined as "high risk" because of a clinical history of hypertension, nephropathy, and unexplained abortions. In 23 of these women who delivered full-term infants with normal weight and status, we found that active renin increased progressively from early pregnancy until the end of the second trimester and then declined slightly thereafter. In contrast, in the remaining six women who had fetal complications consisting of either signs of distress requiring cesarean section or growth retardation, the increase in active renin failed to occur. In all women the levels of inactive renin were more elevated throughout gestation than those observed in nonpregnant women, and were higher, although not significantly, in women without fetal complications than in those with fetal complications. Thus, a blunted activation of the renin system during pregnancy is associated with alteration in fetal development and may possibly contribute to it.Key words: active and inactive renin, pregnancy, fetal outcome.