bluuebunny/crossref_metadata_2025 huggingface dataset:
Dosage effect of streptozotocin on rat tissue enzyme activities and glycogen concentration
Authors: Chen Victor , Ianuzzo C. David
Published: April 2011

The effect of different dosages of streptozotocin (STZ) on selected rat tissue enzyme activities and glycogen concentration were investigated. The rats were administered STZ intravenously at 60 (STZ-60), 80 (STZ-80), 100 (STZ-100), and 150 (STZ-150) mg/kg body weight. They were used 3 weeks postinjection. Mortality prior to kill occurred only in the STZ-100 and STZ-150 rats. All diabetic rats showed reduced growth rate, hyperglycemia, hypoinsulinemia, and hyperlipemia. Phoshofructokinase (PFK) and succinate dehydrogenase (SDH) activities were significantly reduced in the red gastrocnemius muscle of all diabetic rats, and in the white gastrocnemius and soleus of STZ-100 and STZ-150 groups. PFK activity in the heart remained unaltered, but SDH activity was below normal. Liver SDH activity was not affected by insulin deficiency. Glycogen content was markedly increased in the heart and decreased in the liver of all diabetic rats. Glycogen content in the skeletal muscle was similar to the controls, except for the lower values in the soleus of STZ-100 and STZ-150 rats. When STZ-80 and STZ-150 rats were given insulin therapy, the STZ-80 rats showed a greater response to the treatment. Despite similar levels of plasma immunoreactive insulin among all groups of diabetic rats, the STZ-100 and STZ-150 rats had higher mortality, greater loss in body weight, and alterations in enzyme activities and glycogen content in the tissues studied.
In vitro binding of dantrolene to bovine serum albumin and rabbit red blood cell ghosts
Authors: Dehpour A. R. , Mahmoudian M.
Published: April 2011

The binding of dantrolene to rabbit red blood cell (RBC) ghosts and bovine serum albumin as models of receptor sites was studied using fluorescence techniques. Dantrolene upon binding to rabbit RBC ghosts and bovine serum albumin showed fluorescence with emission maxima at 495 and 500 nm, respectively. Dantrolene bound to rabbit RBC ghosts with an association constant of 6.06 × 104 M−1 and there were 2.4 × 106 dantrolene binding sites per ghost. The binding of dantrolene to bovine serum albumin showed an anomaly with respect to dantrolene concentration. Dantrolene at concentrations of 1.25 – 3.75 μM bound to bovine serum albumin with an association constant of 1.72 × 104 M−1 and there were 1.078 binding sites/mol bovine serum albumin. The higher affinity of dantrolene toward blood cells was confirmed by studying the distribution of dantrolene between blood cells and plasma after a single i.p. injection of dantrolene sodium (3 mg/kg) to albino rabbits. It was found that the concentration of dantrolene in rabbit blood cells was 2.76 times that of plasma.
Pressure-dependent action of angiotensin II on glomerular filtration in the isolated rat kidney
Authors: Steele Thomas H. , Gottstein Jeanne H. , Challoner-Hue Laura
Published: April 2011

We examined the action of angiotensin II (AII) on isolated rat kidney perfused with a recirculating cell-free solution at either 12 pKa (90 mmHg) or 17 kPa (128 mmHg). The renal perfusion pressure was maintained constant while sufficient All was added to increase the renal vascular resistance by 50%. In the low-pressure kidneys, AII increased the glomerular filtration rate (GFR) by 155%, increased sodium reabsorption by 157%, and decreased the urine sodium concentration by 34% without affecting sodium excretion. In the high-pressure kidneys, GFR initially was significantly greater but was not affected by AII. In these experiments, AII had no effect on sodium reabsorption or excretion and decreased the urine sodium concentration by 7%. The data suggest that AII could be involved in autoregulation of the GFR without producing large changes in sodium excretion.
Humoral growth factor after small intestinal resection in the dog
Authors: Caussignac Yves , David France
Published: April 2011

The serum of dogs with a 50% proximal small bowel resection is capable of growth stimulation in small intestinal epithelioid cells in monolayer culture. This overstimulation by postresection serum is not seen when dogs undergo either a small intestinal transection or a simple laparotomy or with baby hamster kidney fibroblast cells in culture. The effect does not seem to be represented by a gastrinlike molecule. This study lends support to the hypothesis that a humoral factor is involved in small intestinal adaptation after partial resection.
The enzymatic basis for production by human neutrophils
Authors: Babior Bernard M.
Published: April 2011

[Formula: see text] production is the first step in the generation of a group of powerful microbicidal oxidants by neutrophils. The production of [Formula: see text] is catalyzed by a membrane-bound, NADPH-preferring flavoprotein oxidase, a conclusion supported by much evidence including the discovery of a new form of chronic granulomatous disease caused by a mutation affecting that oxidase directly. Also involved in the [Formula: see text]-forming reaction is a b-type cytochrome; the role of this cytochrome is as yet undefined, though it does not appear to be on the direct route of electron transfer between NADPH and oxygen. It has been postulated that quinones too participate in the [Formula: see text]-forming reaction, but further work is necessary to define their role more fully.
Role of free radicals in catecholamine-induced cardiomyopathy
Authors: Singal P. K. , Kapur N. , Dhillon K. S. , Beamish R. E. , Dhalla N. S.
Published: April 2011

Effects of an antioxidant, vitamin E, and a membrane stabilizing agent, zinc, were examined on the isoproterenol-induced changes in the rat myocardium. Isoproterenol treatment (80 mg/kg given over 2 days in two equal doses) caused arrhythmias and 25% mortality within 24 h of the last injection. The ultrastructural changes in the subendocardium and in focal areas of the subepicardium included swelling of mitochondria, loss of myofibrils, cell necrosis, fibrosis, and infiltration of the affected areas by polymorphonucleocytes. Both creatine phosphate and adenosine triphosphate levels were markedly decreased in hearts from isoproterenol-treated animals. Pretreatment of the animals with vitamin E (10 mg∙kg−1∙day−1 for 2 weeks) or zinc (10 mg/kg ZnSO4, twice a day for 7 days) prevented these deleterious effects of isoproterenol. Animals maintained on vitamin E deficient diet for 8 weeks were found to be more sensitive to isoproterenol-induced changes and this increased sensitivity was reversed by a 2-week feeding of the animals on the normal diet coupled with vitamin E treatment. Based on the data obtained in this study it is proposed that catecholamine-induced changes may involve free radicals, which by promoting lipid peroxidation may increase membrane permeability and lead to the development of cardiomyopathy.
Action directe des antagonistes des minéralocorticoïdes sur la biosynthèse de l'aldostérone : activités comparées de plusieurs nouveaux composés
Authors: Netchitailo P. , Perroteau I. , Delarue C. , Leboulenger F. , Capron M. H. , Vaudry H.
Published: April 2011

Spironolactone is a diuretic steroid which is capable of blocking the binding of aldosterone to its cytosol receptor at the distal convoluted tubule. In addition, it has been shown that spironolactone is a strong inhibitor of steroidogenesis. More recently, new aldosterone antagonists have been discovered. Some of these compounds are more active than spironolactone in competing with aldosterone and have higher specificity for mineralocorticoid receptors. In this study we compare the direct activity of new antimineralocorticoids (SC 23133, SC 19886, SC 26304, and SC 27169) on aldosterone biosynthesis. Marked differences were found in the activity of these compounds upon steroidogenesis. SC 23133 gave rise to a strong inhibiting activity (90%). This activity was reversible (recovery of spontaneous production occurs 150 min after the end of the administration of SC 23133). SC 19886 totally inhibited aldosterone biosynthesis (95%) in a lasting mean. Conversely, SC 27169 and SC 26304 presented no or weak inhibiting effect. Further experiments showed that SC 27169 was unable to block the stimulation of aldosterone biosynthesis induced by corticotropic peptides, whereas the administration of SC 23133 and SC 19886 totally suppressed the stimulatory effect of ACTH and angiotensin II. Owing to the important stimulation of the renin–angiotensin system induced by antimineralocorticoid treatment, these results suggest that SC 23133 and SC 19886 will exert a higher antinatriuretic activity than SC 27169.
Mechanisms of action of neurotensin on motility of canine gastric corpus in vitro
Authors: McLean J. , Fox J. E. T.
Published: April 2011

Increasing concentrations of neurotensin produced a biphasic contractile response, inhibition followed by excitation, when added to full-thickness circular strips of canine gastric corpus muscle cut in a circular orientation and incubated at 37 °C in vitro. The inhibitory response (mean effective concentration (EC50) 7 × 10−9 M) was not altered by addition of concentrations of tetrodotoxin or scorpion venom sufficient to block field-stimulated neural responses nor by any other antagonist tested. Therefore, it would appear that inhibition is due to an excitation of the smooth muscle receptor. The excitatory response (EC50 4 × 10−7 M) was only present in full-thickness strips, i.e., was absent in strips of circular muscle, and was reduced by mepyramine or histamine tachyphylaxis. Pretreatment with disodium cromoglycate or repeated doses of 48/80 to extinction of the response completely eliminated the excitatory response as did repeated doses of substance P to tachyphylaxis. Since 48/80 and substance P have been shown to degranulate mast cells and disodium cromoglycate to stabilize mast cell membranes, neurotensin would appear to produce excitation by releasing histamine and other material from mast cells. In contrast to in vivo studies, where two classes of receptors producing inhibition were found, i.e., a high-affinity receptor on adrenergic nerves and a lower affinity receptor on smooth muscles, in vitro there appears to be only one class of receptor producing inhibition on the smooth muscle itself as no neural receptors were found. The neurotensin receptor responsible for excitation appeared to be on mast cells. The action of neurotensin thus depends upon the locus and the affinity of the receptor and the presence of the receptor on the method of study, i.e., in vivo vs. in vitro.
Medial elastin in the thoracic and abdominal aorta of sheep and lambs
Authors: Baardwijk Charles van , Roach Margot R.
Published: April 2011

Aortas were removed from six mature lambs and four sheep and pressure fixed at 100 and 120 mmHg pressure (1 mmHg = 133.322 Pa), respectively, in 10% buffered formalin. The numbers of elastin layers were counted from cross sections at different distances down the aorta, from the distal arch to the iliac bifurcation, and showed a linear decrease in the thoracic aorta. In the abdominal aorta there was no difference in values from the diaphragm to the aortoiliac bifurcation in the lamb, but a slight decrease in the sheep. If y = mx + b, where y is the number of medial lamellar units (MLU), b the intercept, x the distance from the last brachiocephalic branch in centimetres, and m the slope, we obtained the following equations (with standard deviations): lamb thoracic aorta; y = −6.29 (±0.71)x + 106 (±12); sheep thoracic aorta; y = −3.46 (±0.40)x + 140 (±21.4); lamb abdominal aorta; y = 0.51 (±1.48)x + 37 (±7.7); sheep abdominal aorta; y = −0.85 (±0.28)x + 66 (±5.9). Tension per lamellar unit was calculated and plotted versus distance yielding a linear increase in the entire lamb aorta but an abrupt increase between thoracic and abdominal aortas in the sheep. This causes the pulse wave to move uniformly with increasing speed along the length of the lamb aorta but would cause an abrupt change in the wave at or about the diaphragm in the sheep. Distortions in the pulse wave could produce local stress concentrations in the abdominal aorta which might render it more susceptible to atherosclerosis than the thoracic aorta.
Natriuretic activity of extracts obtained from hearts of different species and from various rat tissues
Authors: Bold Adolfo J. de , Salerno Tomas A.
Published: April 2011

Heart tissue extracts from different species as well as extracts obtained from various rat tissues were tested for natriuretic activity in the nondiuretic bioassay rat. Natriuretic activity was found restricted to heart tissues. Atrial but not ventricular extracts of mammals and both atrial and ventricular extracts in the frog displayed natriuretic activity. Specific natriuretic activity values were highest in the atria of small rodents. It is concluded that the distribution and relative content of natriuretic activity of cardiac tissues from different species approximately parallels the distribution and relative abundance of specific heart granules.
Calcium-dependent release of acetyl-coenzyme A from liver mitochondria
Authors: Benjamin A. M. , Murthy Ch. R. K. , Quastel J. H.
Published: April 2011

Calcium ions (10 μM) enhance the permeability of the hepatic inner mitochondrial membrane to acetyl-CoA (and CoA). This effect is suppressed by the absence of phosphate ions or by the presence of EGTA, La3+, or ruthenium red. Exposure of mitochondria to Ca2+ for short intervals of time (e.g., 10 min) results in a reversible permeability change with release of acetyl-CoA and retention of sensitivity to EGTA. It is suggested that conditions resulting in an increase of the calcium ion concentration in the cytoplasm may thereby increase the rate of transfer of acetyl-CoA from the mitochondria to the cytoplasm.
Increased contractility in vascular smooth muscle of dystrophic hamsters
Authors: Hunter E. G. , Elbrink J.
Published: April 2011

To investigate the "vascular" hypothesis of muscular dystrophy, the sensitivity and contractility of aortic spiral strips of dystrophic (BIO 14.6) and normal (FIB) hamsters have been determined to various smooth muscle agonists. The results obtained with cumulative dose–response curves show that there is no increase in the sensitivity of the dystrophic compared with the normal aorta to noradrenaline, phenylephrine, isoproterenol, histamine, or 5-hydroxytryptamine. However, there was a significant increase in the force generated by aortic strips of the dystrophic animals to all agonists. Determination of noncollagen and collagen protein showed that there was no difference in the relative proportions of these proteins in the aortas from the two strains. The results show that in this animal model of dystrophy an increased response to vasopressor amines occurs and is in accordance with that expected of the vascular hypothesis.
Absence of supernormal conduction in canine myocardium
Authors: Carson D. Leigh , Dresel Peter E.
Published: April 2011

Transmural conduction time, measured as the difference in arrival time of impulses from a distant stimulating site at endocardial and epicardial electrodes near the left ventricular apex, has been reported to decrease when closely coupled extrasystoles are interpolated, indicating that muscle conduction could be supernormal. We have now determined that reduction in transmural conduction time is accounted for completely by the relatively late arrival time of the extrasystolic wave front at the endocardial recording site. The endocardial recording site was activated later than an immediately adjacent site within the wall in two out of eight animals, which could be interpreted as retrograde conduction. No evidence for supernormal conduction within the ventricular wall could be obtained by multiple electrode recordings. Supernormal conduction throughout the myocardial wall could not be demonstrated on stimulation of the endocardial site. We conclude that supernormal conduction in myocardial muscle cannot be demonstrated and that changes in transmural conduction time do not always measure myocardial conduction velocity.
Stimulation of calcium pump activity in heart sarcolemma by timolol
Authors: Dzurba Andre , Ganguly Pallab K. , Beamish Robert E. , Dhalla Naranjan S.
Published: April 2011

The effects of β-adrenergic blocking agents, timolol and atenolol (1–1000 μM), were studied on rat heart sarcolemmal ATPase and Ca2+ binding activities. Timolol, unlike atenolol, increased both Ca2+-stimulated ATPase and ATP-dependent Ca2+ binding; the maximal effects were seen at 1 μM concentration of timolol. Both timolol and atenolol did not alter the sarcolemmal Mg2+ ATPase and nonspecific Ca2+ binding activities. Sarcolemmal Ca2+ -stimulated ATPase was also activated by concanavalin A (6–66 μg/mL) which is known to alter membrane fluidity; however, Mg2+ ATPase was unaffected by this agent. These results indicate that timolol may stimulate Ca2+ pump activity in heart sarcolemma by changing membrane fluidity in a manner similar to that of concanavalin A.
Kallikrein concentration in submandibular glands of rats chronically treated with isoproterenol
Authors: Gutkowska Jolanta , Thibault Gaétan , Cantin Marc , Garcia Raul , Genest Jacques
Published: April 2011

The effect of chronic β-adrenergic stimulation with isoproterenol on the kallikrein content of rat submandibular gland was estimated by radioimmunoassay, by immunohistochemistry, and by analytical isoelectric focusing. Radioimmunoassays revealed that the kallikrein content of the submandibular gland was already significantly decreased after 6 days of treatment. After 21 days, the kallikrein content was 40 times lower and by 33 days an almost complete depletion was found. These findings were confirmed by immunohistochemistry. Analytical isoelectric focusing also showed that, after 33 days of treatment, the typical bands corresponding to the kallikrein isoenzymes of the submandibular gland had disappeared. These results indicate that kallikrein secretion is influenced by β-adrenergic stimulation.
Potentiation of the actions of insulin by taurine
Authors: Lampson W. G. , Kramer J. H. , Schaffer S. W.
Published: April 2011

Taurine was found to mediate several changes in myocardial metabolism. In the absence of insulin, only oxygen consumption was significantly elevated by taurine; however, in the presence of 2.5 U/L insulin the amino acid caused the stimulation of glycolysis and glycogenesis, as well as oxygen utilization. These effects of taurine were shown to be dependent on insulin concentration, suggesting a link between the two substances. Measurements of key metabolic intermediates revealed that taurine stimulated glycolysis by enhancing flux through phosphofructokinase. Similarly, it was shown that glycogenesis was promoted because of the increase in glycogen synthase I and decrease in phosphorylase a activity. Several possible mechanisms for the observed changes are discussed.
Some red blood cell geometry
Authors: Vayo H. Westcott
Published: April 2011

Formulas are presented for the cross-sectional area, volume, surface area, and circumference of a model red blood cell based on the Oval of Cassini as the geometry of choice. The relationship between the actual cell dimensions and model parameters is given as is the criterion for the validity of the model used in the formulary. Each formula is given in rectangular form and in a form suitable for computer calculations.
Uptake and release of calcium by canine gastric corpus smooth muscle plasma membrane enriched fraction
Authors: Sakai Yasushi , Grover Ashok K. , Fox Jo-Ann E. T. , Daniel Edwin E.
Published: April 2011

Calcium movements across plasma membrane enriched vesicles isolated from canine gastric corpus smooth muscle were investigated. The ATP-dependent Ca2+ uptake increased with time up to 10 min. The uptake for the initial 2-min period was approximately linear with time. The apparent initial velocity of the ATP-dependent Ca2+ uptake increased monotonically with free Ca2+ concentration from 0.1 to 2 μM, and further increases in free Ca2+ concentration did not increase the Ca2+ uptake. The free Ca2+ dependence curve could be described with a Hill coefficient of approximately 1.0 and Km of 0.85 ± 0.01 μM for free Ca2+ concentration. Passive Ca2+ uptake (reaction time = 1 h) also increased with increasing free Ca2+ concentrations from 0.02 to 4.0 mM. Dilution of loaded vesicles in isotonic media containing EGTA led to initial rapid loss (< 1 min) followed by a slower release which showed simple exponential decay. The t1/2 values of the slower Ca2+ loss from these vesicles were 16.1 ± 0.9 min (actively loaded n = 5) and 18.4 ± 0.9 min (passively loaded n = 3), respectively. Dilution in isotonic medium containing both EGTA and A23187 released all the sequestered Ca2+ from these loaded vesicles.
Studies of the mechanism of passive anaphylaxis in human airway smooth muscle
Authors: Davis C. , Jones T. R. , Daniel E. E.
Published: April 2011

This investigation was carried out to study allergic contraction of passively sensitized human airway smooth muscle in response to specific antigen challenge. We attempted to determine the role played by histamine, slow reaction substances (SRSs), and cyclooxygenase products in the mediation of this response in tracheal smooth muscle. Tissues were passively sensitized with serum from ragweed-sensitive patients (15 h, 4 °C). Subsequent challenge with ragweed antigen produced a slowly developing contraction. The peak contraction to a dose producing a maximal response was 37 ± 6% of the carbachol maximum. Mepyramine (5 × 10−6 M) did not alter the contraction. Methylprednisolone (2 × 10−5 M) attenuated the response to antigen but had no significant effect on the contractile response to arachidonic acid. Indomethacin (5.6–28 × 10−6 M) enhanced the peak antigen-induced contractions by 25 ± 11% whereas 5, 8, 11, 14-eicosatetraynoic acid (6.4 × 10−5 M) selectively attenuated the antigen-induced contraction by 86 ± 12%. Nordihydroguarietic acid (6–12 × 10−6 M) attenuated both the antigen plus arachidonate induced responses. FPL-55712 (1–2 × 10−6 M) antagonized the contractions to antigen. Compound 48/80 and goat antihuman immunoglobulin E produced similar slowly developing contractions in sensitized and in some nonsensitized tissues. These responses, except for an early component of the response to 48/80, were independent of histamine and were reversed by FPL-55712. These findings suggest that arachidonic acid metabolites mediate (slow reacting substances) and modulate (prostaglandins) allergic contraction of human airway smooth muscle while any histamine released contributes little or nothing to the contraction in the larger airways.
The kinin system and ovulation: changes in plasma kininogens, and in kinin-forming enzymes in the ovaries and blood of rats with 4-day estrous cycles
Authors: Smith Caroline , Perks A. M.
Published: April 2011

Rats with 4-day estrous cycles showed a 51% fall in plasma kininogen in early proestrus (1200–1500). Levels remained depressed throughout ovulation, and then recovered steadily. The initial fall corresponded well with the LH surge. Initial attempts were made to detect enzymes which might be responsible for the change. Kinin-forming enzymes, in either precursor or active forms, were absent from the ovaries in diestrus, but appeared at the onset of the fall in kininogen (kinin-forming activity, 2.87 ± 0.83 ng bradykinin (BK) equiv.∙g wet tissue−1∙min−1). They rose 10-fold just before ovulation, and then declined rapidly. This major peak, and a corresponding one in plasma, may have reflected the presence of follicular proteases. Plasma kinin-forming enzymes showed no apparent change when the kininogen first declined. They then disappeared, suggesting a more delayed activation and destruction. It seems possible that LH induces kinin-forming enzymes in the ovaries, and induces a later activation of plasma enzymes, to produce kinins which may be involved in vascular and permeability changes important in ovulation, and perhaps concerned in the mechanisms of positive feed-back with the pituitary.
Interaction of histamine with noradrenergic constrictory mechanisms in cat cerebral arteries and veins
Authors: Gross Paul M. , Harper A. Murray , Teasdale Graham M.
Published: April 2011

We examined responses of pial arteries and veins in situ to noradrenergic stimuli in the presence of histamine. Electrical stimulation of sympathetic nerves and perivascular microapplication of norepinephrine in mock cerebrospinal fluid produced constriction of arteries and veins in anesthetized cats. During simultaneous perivascular injection of histamine, these noradrenergic responses were attenuated or reversed. In both arteries and veins, constriction from sympathetic nerve stimulation was prevented by simultaneous application of the histamine receptor agonists, pyridylethylamine (H1) or impromidine (H2), results that suggest interference involving both types of histamine receptors. In arteries, impromidine, but not pyridylethylamine, inhibited constriction resulting from exogenous norepinephrine. Our findings indicate that histamine may have an inhibitory influence, exerted through both receptor types, on noradrenergic mechanisms in cerebral vessels.
Inhibition of shivering during restraint hypothermia
Authors: Shimada Steven G. , Stitt John T.
Published: April 2011

Restraint hypothermia has often been described, but its cause has never been clarified. We hypothesized that it might be due to a suppression of shivering thermogenesis. Thus, we restrained conscious rats in an ambient temperature of 2 °C while measuring rectal (Tre) and tail skin temperatures, metabolic rate (MR), and shivering activity. When rats were cold exposed but not restrained, Tre fell 1.4 ± 0.2 °C (SE) during the 1st h. When these same rats were restrained, Tre fell at a rate of 6.5 ± 0.2 °C/h. MR averaged 15.7 ± 1.4 W/kg for the unrestrained rats, but it averaged only 9.0 ± 1.1 W/kg for the restrained rats. The restrained rats showed no signs of shivering. The animals were then subjected to a restraint adaptation regimen and then reexposed to cold. Restraint now produced a fall in Tre of only 2.6 ± 0.7° C/h. The animals shivered and generated an MR of 15.8 ± 0.9 W/kg. Naive rats became hypothermic because restraint suppressed shivering activity. However, adapted rats continued to shiver and remained normothermic. We suggest that a stressful or threatening situation, such as restraint for a naive rat, inhibits shivering and leads to hypothermia in a cold environment. This would not occur in adapted rats because restraint is no longer stressful.
Effects of oral propranolol and exercise protocol on indices of aerobic function in normal man
Authors: MacFarlane B.J. , Hughson R. L. , Green H. J. , Walters D. J. , Ranney D. A.
Published: April 2011

The exercise responses to two different progressive, upright cycle ergometer tests were studied in nine healthy, young subjects either with no drug (ND) or following 48 h of oral propranolol (P) (40 mg q.i.d.). The ergometer tests increased work rate by 30 W either every 30 s or every 4 min. Propranolol caused a significant (p < 0.05) reduction in peak oxygen uptake ([Formula: see text] during both the 30-s and 4-min tests (30-s ND, 3949 ± 718 mL∙min−1[Formula: see text]; 30-s P, 3408 ± 778 mL∙min−1; 4-min ND, 4058 ± 409 mL∙min−1; 4-min P, 3725 ± 573 mL∙min−1). There was no difference between 30-s ND and 4-min ND for peak [Formula: see text]. The ventilatory anaerobic threshold was not significantly different between any test (30-s ND, 2337 ± 434 mL O2∙min−1; 30-s P, 2174 ± 406 mL O2∙min−1; 4-min ND, 2433 ± 685 mL O2∙min−1; 4-min P, 2296 ± 604 mL O2∙min−1). The [Formula: see text] at which blood lactate had increased by 0.5 mM above resting levels was significantly lower than the ventilatory anaerobic threshold for the 4-min ND (1917 ± 489) and the 4-min P (1978 ± 412) tests, but was not different for the 30-s ND and 30-s P tests. At exhaustion in the progressive tests, the blood [Formula: see text] was higher (p < 0.05) in both 30-s tests than 4-min tests. Steady-state submaximal cardiac output was reduced (p < 0.05) by propranolol. This was primarily due to a decrease in heart rate as stroke volume was significantly greater with propranolol than with no drug (p < 0.05). The duration of time at each stage of work rate in progressive exercise did not significantly affect the peak [Formula: see text] or the [Formula: see text] at the ventilatory anaerobic threshold. Short duration stages were associated with lower blood lactates for a given submaximal [Formula: see text] and with higher blood [Formula: see text] at exhaustion. Propranolol had no significant effect on ventilatory anaerobic threshold or [Formula: see text] at a 0.5 mM blood lactate increase; however, propanolol did significantly reduce the peak [Formula: see text]. It is concluded that in submaximal exercise, the cardiorespiratory system can compensate for propranolol induced changes. Above the anaerobic threshold, these compensations are inadequate.
In vitro studies on cetamolol, a new potent cardioselective β-adrenoceptor blocking agent with intrinsic sympathomimetic activity
Authors: Grimes D. , Stern M. , Wojdan A. , Cummings J. R.
Published: April 2011

In vitro studies on the new β-adrenoceptor antagonist, cetamolol (Betacor®), have demonstrated that the compound is a potent antagonist of the chronotropic effects of isoproterenol on guinea pig atria. The pA2 value (8.05) of cetamolol was slightly lower than that of propranolol (8.44). The compound was shown to possess a moderate degree of cardioselectivity as indicated by a lower pA2 value for the antagonism of isoproterenol-induced relaxation of the isolated guinea pig trachea (pA2 = 7.67) compared with that derived from atrial experiments (pA2 = 8.05). Up to concentrations of 10−4 M, cetamolol displayed negligible negative inotropic activity relative to propranolol in the electrically stimulated guinea pig left atrial preparation. When applied to isolated right atria from reserpinized rats, cetamolol had a positive chronotropic effect (approximately 75% of that displayed by practolol) which was antagonized by pretreatment with propranolol, thus indicating intrinsic sympathomimetic activity. Specificity experiments in a number of isolated tissues indicated that cetamolol had very little antihistaminic, anticholinergic, α1-adrenergic blocking, or calcium antagonistic properties. Biochemical receptor binding studies are in general agreement with the observations from the isolated tissue experiments.
Effects of desmethylimipramine and normetanephrine on calorigenic response and plasma noradrenaline concentration in warm- and in cold-acclimated rats exposed to cold
Authors: Chan Chi-Chung , Depocas Florent
Published: April 2011

Oxygen consumption and plasma noradrenaline concentration were increased significantly above resting levels in warm-acclimated and in cold-acclimated rats exposed to an ambient temperature of 4 °C. Administration of normetanephrine (1 μg∙min−1∙g body weight−0.74), but not of desmethylimipramine (1 mg∙kg−1), resulted in higher resting plasma noradrenaline levels at 24 °C and increased the length of time required for the oxygen consumption to return to resting levels after cold exposure in both acclimation groups. These observations support a significant role of extraneuronal uptake in noradrenaline inactivation under normal physiological conditions. Calorigenic responses to cold exposure were not affected at all by treatment of animals with desmethylimipramine and (or) normetanephrine in either warm-acclimated or cold-acclimated rats, although an enhancing effect of these uptake inhibitors on plasma noradrenaline was evident in cold-acclimated rats. It is suggested that a peripheral–central thermoregulatory mechanism adjusts activation of thermogenic effectors so as to maintain a steady calorigenic response, appropriate to the thermal demand of the environment, to compensate for changes in perineuronal concentration of noradrenaline in sympathetic thermoeffectors owing to blockade of extraneuronal uptake.
Comparison of the effects of forskolin and isoproterenol on cyclic AMP levels and tension in bovine coronary artery
Authors: Vegesna Raju V. K. , Diamond Jack
Published: April 2011

The effects of isoproterenol and forskolin on cyclic AMP levels and tension were compared in helical strips of bovine coronary artery. Both compounds produced time- and dose-dependent increases in cyclic AMP levels and both compounds relaxed potassium-contracted arteries. However, in contrast to the results with isoproterenol, cyclic AMP elevation and relaxation were not well correlated at lower concentrations of forskolin. For example, 0.1 μM forskolin increased cyclic AMP levels in the arteries by approximately 5.5-fold but did not relax the muscles. A smaller elevation of cyclic AMP produced by 1.0 μM isoproterenol, on the other hand, was accompanied by an almost complete relaxation of the arteries. These results suggest that either cyclic AMP is not responsible for the relaxation caused by these agents, or some form of functional compartmentalization of cyclic AMP exists in this tissue.
Age-dependent changes in electrophysiologic characteristics of fast and slow action potentials in rat papillary muscle
Authors: Kojima Michio , Sperelakis Nick , Johnson Gordon , Ehrreich Stewart , Balazs Tibor
Published: April 2011

Isolated papillary muscles from juvenile (about 2 months old, average weight of 250 g) and young adult rats (about 4 months old, average weight 485 g) were studied for age-dependent differences in the characteristics of fast and slow action potentials (APs). The fast and slow APs were recorded in 5.4 mM and 25 mM K+-Tyrode solutions, respectively (stimulation rate of 1 Hz). For the slow APs, the dose–response curves for isoproterenol versus [Formula: see text] (the maximum rate of rise of the APs), overshoot, and AP amplitude were linear between 10−9 M and 10−6 M (10−5 M in some cases) in the juvenile and young adult rats. Isoproterenol pretreatment (1 mg/kg s.c, 1 h prior) decreased the slope of the dose–response curve, and saturation was achieved at a lower concentration. The [Formula: see text], overshoot, and amplitude of both the fast and slow APs were somewhat smaller in the young adult rats than in the juvenile rats; there were no differences in the resting potential, AP duration, or threshold voltage. These results suggest that activation of a greater fraction of the β-adrenergic receptors is coupled directly or indirectly to activation of a greater fraction of the slow channels. The pretreatment data suggest that down-regulation of the β-adrenergic receptor may occur. The conductance per channel for the fast Na+ channels and slow channels, and (or) the number of both types of functional channels, may decrease with age.
Microvascular evidence for a transition zone around a chronic myocardial infarct in the rat
Authors: Przyklenk K. , Groom A. C.
Published: April 2011

Muscle fibers in the transition zone of an infarcted heart are thought to be potentially ischemic during the first 6–9 h following coronary artery occlusion. However, the long-term fate of the muscle fibers at the margin of the necrosis is uncertain. Ischemia implies reduced oxygenation, possibly owing to a reduced capillary supply; thus our objective was to determine whether a region of reduced microvascular supply exists at the margin of a necrosis produced by chronic coronary artery occlusion. Five variables were used to quantitate the capillary supply in the transition zone: C/F (capillary to fiber) ratio, Vf (number of vessels around a fiber), Fv (number of fibers surrounding a vessel), capillary density, and fiber diameter. Infarcts were induced in young male rats by ligating the left coronary artery midway between its origin and the apex of the heart. Five weeks later, the capillary supply in the transition zone was significantly below control values, i.e., significant reductions in C/F, Vf, and Fv were found. This region of reduced capillary supply extended 225–525 μm laterally from the edge of the necrosis. Thus, a narrow transition zone, defined as a region of viable muscle fibers with a subnormal microvascular supply, exists as long as 5 weeks following coronary artery occlusion in the rat.
The medullary respiratory neurons: a review
Authors: Long Susan E. , Duffin James
Published: April 2011

The medullary respiratory neurons involved in the generation of respiratory rhythm are reviewed. The subject is introduced by a brief description of the history of respiratory neurophysiology and of the pontine respiratory neurons. A detailed neurophysiological review is presented for the medullary respiratory neurons: their locations, morphology, firing patterns, afferent connections, axonal connections, and functional interrelations. The significance of the medullary respiratory neurons for rhythmogenesis is discussed.
The protective effects of D-600 and propranolol on reperfusion injury in the anaesthetized rabbit
Authors: Moore Margo M. , Godin David V.
Published: April 2011

The ability of a calcium channel blocker (D-600) and a β-adrenergic antagonist (propranolol) to modify the chemical, biochemical, functional, and ultrastructural manifestations of reperfusion injury following circumflex coronary artery ligation has been examined using an open chest, anaesthetized rabbit model of acute myocardial ischaemia. A 40-min ligation period followed by 60 min of reperfusion produced a decrease in mitochondrial azide-sensitive ATPase activity which could be prevented by pretreatment with either agent. While both drugs caused an equivalent (approximately 50%) reduction in myocardial Ca2+ accumulation associated with reperfusion, only D-600 preserved Mg2+ and Na+ levels. The greater protective effects of D-600 on sarcolemmal integrity were also apparent from its superior ability (when compared with propranolol) to offer protection against the loss of sarcolemmal Na+–K+ ATPase activity which we have previously suggested may parallel the development of irreversible ischaemic injury. Further support for these biochemical data came from ultrastructural studies in which we demonstrated significant improvement in subcellular membrane integrity by both of the drugs. In contrast to the foregoing protective actions, D-600 and propranolol failed to prevent the marked decrease in myocardial contractile function and in cellular ATP content associated with reperfusion. In conclusion, our studies have shown that both D-600 and propranolol can limit the injury caused by ischaemia and reperfusion. The superior effectiveness of D-600 in our system cannot be explained on the basis of Ca2+ antagonism alone, but is more likely a result of its greater negative inotropism.
Energy balance following sympathetic denervation of brown adipose tissue
Authors: Dulloo A. G. , Miller D. S.
Published: April 2011

The effects of sham, bilateral surgical denervation or excision of interscapular brown adipose tissue on body composition and energetic efficiency were studied in young CFLP mice kept at 25 °C and fed a laboratory stock diet. A preliminary experiment showed that 15 weeks following surgery, total body fat was increased by 42% in the denervated group and by 72% in the excised group while body protein was unchanged. In another 7-week energy balance experiment, body fat was also significantly higher by 15 and 18% in the denervated and excised group, respectively, but metabolizable energy intake was slightly lower than that of sham controls. Determination of energy expenditure both by the comparative carcass slaughter technique and by measurement of daily oxygen consumption showed that the metabolic rate was reduced in the denervated and excised groups. The capacity for thermogenesis, as measured by an increase in oxygen consumption following injections of noradrenaline (600 μg/kg body weight) was similar in all groups. These studies show that denervation or excision of interscapular brown adipose tissue causes an elevation in energetic efficiency, and indicates an important role of the sympathetic nervous system in the regulation of animal heat production by brown adipose tissue and in the overall control of thermogenesis.
Aniline hydroxylation and 7-ethoxycoumarin O-deethylation activities in solubilized and partially resolved liver cytochromes P-450 from ethanol-fed rats
Authors: Plourde V. , Hétu C. , Joly J.-G.
Published: April 2011

Chronic ethanol administration in female rats enhances the apparent molar activity of liver microsomes for aniline hydroxylation and 7-ethoxycoumarin O-deethylation. Microsomal cytochromes P-450 from ethanol-fed and control rats have been solubilized and partially resolved in six fractions by anion-exchange chromatography. Induction of aniline hydroxylase activity by ethanol was associated with marked increases in the turnover numbers of the more basic cytochrome P-450 containing fractions in a reconstituted aniline hydroxylation system. Cytochrome P-450, exhibiting by far the highest 7-ethoxycoumarin O-deethylase activity, was eluted in a relatively acidic fraction; its turnover number with 7-ethoxycoumarin after ethanol consumption, however, did not differ significantly from that of the corresponding fraction from control microsomes. These observations suggest that induction of liver microsomal mixed function oxidases by ethanol may reflect the contribution of more than one cytochrome P-450 isozyme.
The sites of action of praziquantel in a smooth muscle of Lymnaea stagnalis
Authors: Gardner D. R. , Brezden B. L.
Published: April 2011

Praziquantel (1.6 × 10−6 M), a new anthelmintic drug, was shown to produce a sustained contracture in the penis retractor muscle of the freshwater snail Lymnaea stagnalis. Calcium-free saline greatly reduced the magnitude and duration of the praziquantel contractures if the preparation had been previously exposed to praziquantel. The praziquantel contracture in zero-calcium saline was abolished if the preparation was pretreated with successive applications of 2 × 10−2 M caffeine. Lanthanum (1.0 mM) in zero-calcium saline prevented the contractures normally produced by 30 mM potassium saline, but did not prevent the praziquantel contracture. In normal saline, however, 1.0 mM lanthanum greatly reduced the magnitude of a praziquantel-induced contracture. We conclude that praziquantel increases sarcolemmal calcium permeability and releases calcium from intracellular stores in Lymnaea stagnalis smooth muscle.
Opiate modulation of thermoregulation in adult Pekin ducks
Authors: Thornhill J. A. , West N. H.
Published: April 2011

Lightly restrained, adult Pekin ducks (2–3 kg) were given a subcutaneous (sc) injection of either sterile saline or morphine sulphate (10 or 30 mg/kg), followed 90 min later by a sc injection of naloxone hydrochloride (10 mg/kg). Core (cloacal TC) and surface (web TW) temperatures were continuously monitored along with heart (fH) and respiratory rates (fresp). In a related study, another group of Pekin ducks was placed in an open respirometer chamber so that oxygen consumption [Formula: see text] could be determined following administration of sterile saline or morphine. Morphine sulphate (10 and 30 mg/kg) caused a hyperthermic core temperature response which persisted over the 90-min test period. This hyperthermia was due to an initial but transient vasoconstriction of the peripheral vasculature, as inferred from the sudden drop in foot web temperature. It was also found that morphine rapidly enhanced [Formula: see text] of the ducks, which remained elevated throughout the entire 90-min postmorphine injection period. TWs began to increase as peak TCs were reached ([Formula: see text] postinjection), and were above control levels until the end of the morphine period. fH was elevated following morphine administration but fresp was not altered. Upon naloxone administration, TCs were reduced because heat production was decreased ([Formula: see text] fell) and heat dissipation was enhanced further by increased vasodilatation (elevated TW) and a substantial (> 10-fold) increase of fresp (gular fluttering). Results demonstrate that morphine caused hyperthermic TC changes in adult Pekin ducks by increasing heat production while, at the same time, minimizing heat loss by vasoconstricting the peripheral vasculature and inhibiting respiration.
A Ca2+-dependent mechanism for the positive inotropic response to an increase in afterload in cat papillary muscle
Authors: Wahler Gordon M. , Swayze Claude R. , Fox Irwin J.
Published: April 2011

In cat papillary muscles, under control conditions (1.25 mmol/L Ca2+ bathing solution, 25 °C), increasing the afterload by switching from isotonic to isometric contraction elicited a positive inotropic response. Halving the bath [Ca2+] resulted in a percentagewise similar or greater positive inotropic response to increased afterload, while doubling the bath [Ca2+] reduced and caffeine abolished or reversed this response, indicating [Ca2+]i predictably influences it. Since it was markedly reduced by verapamil and unaffected by propranolol, the positive inotropic response to increased afterload was concluded to be largely due to increased Ca2+ influx, unrelated to catecholamine release, caused by increased mean muscle length over time owing to the changing from isotonic to isometric contraction. While at 25 °C, increasing the afterload caused a positive inotropic response at 12 to 48 stimulations/min, at 37 °C and at similar frequencies, a negative inotropic response occurred. This reversed to a positive inotropic response at 86 stimulations/min, well below the normal cat heart rate, suggesting an increased afterload would cause a positive inotropic response via this mechanism in vivo, as observed for years in intact mammalian hearts. Similarities between positive inotropic responses to increased afterload in isolated cardiac muscle, isolated hearts, and intact animals indicate all may be examples of the same phenomenon (Anrep effect).
The cardiovascular effects of hypertonic sodium bicarbonate in conscious dogs: underlying mechanisms of action
Authors: Dumont Louis , Stanley Paul , Chartrand Claude
Published: April 2011

Mechanisms underlying the transient hypotensive effect (central or peripheral) of rapid bolus administration of hypertonic sodium bicarbonate (NaHCO3) were studied in conscious dogs. Thirteen animals equipped with an electromagnetic flow probe positioned around the ascending aorta were utilized. NaHCO3 (18.5 mequiv. of 1786 mosmol/L), hypertonic saline solution having the same sodium concentration as NaHCO3, and mannitol solution with the same osmolarity as NaHCO3, were injected in the right and in the left atrium. Intra-arterial NaHCO3 was tested to assess its direct peripheral vascular effects. Blood ionic as well as acid–base modifications following NaHCO3 were also studied. Our results indicate that right atrial injection of NaHCO3 elicited transient hypotension (−10 to −15 mmHg (1 mmHg = 133.322 Pa)) and myocardial depression as revealed by a significant decrease of stroke volume (−8%), stroke power (−18%), stroke work (−12%), maximum systolic flow (−13%), peak velocity (−13%), and maximum acceleration (−24%). When the solution is injected in the left atrium, myocardial depression is more pronounced suggesting that the coronary bed is the site of action. Hypertonic saline injections indicate that the sodium load plays a role in this decrement of myocardial function while hyperosmolarity per se, as exemplified with mannitol injections, elicits no negative effect. Transient ionic as well as acid–base disturbances are other mechanisms that have to be considered along with coronary vasoconstriction. Decrement in peripheral resistance appears only with right intra-atrial NaHCO3 suggesting that the pulmonary vascular bed is the origin of this reflex.