bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucose-induced insulin release during acute and chronic hypoxia.
Authors: Baum D , Griepp R , Porte D
Published: December 2017

Glucose-induced insulin release was studied in young dogs during acute and chronic hypoxia, alone and in combination. Six experimental animals were rendered chronically hypoxic (PaO2, 43.4 +/- 0.5 torr) by creation of a right-to-left shunt at age 6-8 wk. Six control animals underwent sham procedures (PaO2, 85 +/- 2.2 torr) at the same age. During air breathing, glucose-induced plasma insulin increases were similar in chronically hypoxic and control animals. When severe hypoxia was acutely produced by ventilation with low-oxygen mixtures in experimental (PaO2, 23.7 +/- 1.7 torr) and control animals (PaO2, 26.3 +/- 1.0 torr), plasma insulin responses were markedly inhibited in both. On the other hand, acutely lowering oxygen tensions of control animals (PaO2, 37.5 +/- 1.4 torr) to levels close to those of air-breathing chronically hypoxic animals did not affect the insulin responses. These observations suggest that glucose-induced insulin release is inhibited by acute severe hypoxia despite previous chronic oxygen deficiency. In contrast, moderate hypoxia, acute or chronic, does not appear to affect the insulin response to a glucose load.
Somatostatin effects on lower esophageal sphincter function.
Authors: Bybee D E , Brown F C , Georges L P , Castell D O , McGuigan J E
Published: December 2017

The effect of somatostatin (GH-RIH) infusion (2 microgram/min) on lower esophageal sphincter pressure (LESP) responses to various stimuli was evaluated in adult male baboons. GH-RIH infusion did not affect basal LESP, but did cause a significant suppression of mean immunoreactive insulin (IRI) to 5.8% of basal values (P less than 0.05). Pentagastrin IV caused dose-related increases in LESP that were unaffected by GH-RIH. Abdominal compression caused a threefold rise in LESP (P less than 0.005) both without and with GH-RIH. However, atropine (20 microgram/kg iv bolus) completely blocked this cholinergic LES pressure response. Intragastric alkali as well as intragastric glycine caused significant increases in LESP (P less than 0.05). These LESP responses to alkali and to glycine were totally abolished by GH-RIH. In conclusion, GH-RIH infusion in the baboon does not affect basal LESP, LES smooth muscle response to exogenous stimulation, nor a cholinergically mediated LES response. GH-RIH does inhibit the response of LESP both to intragastric alkali and to glycine by the apparent suppression of a hormonally mediated mechanism.
Intracellular pH measurements in gastric mucosa.
Authors: Hersey S J
Published: December 2017

Intracellular pH was measured in bullfrog gastric mucosa using a pH-indicator dye, bromthymol blue (BTB), with a spectrophotometric technique. Studies showed that BTB is taken up by the gastric mucosa and bound to intracellular components. The binding of BTB was shown to cause a shift in the pKa of the dye from the solution value of 6.95 to a value of 8.0. During the nonsecreting state, intracellular pH was estimated to be 7.4 (metiamide inhibition) or 7.1 (SCN inhibition). During active secretion of acid, intracellular pH increased with increasing secretion rates, reaching values in excess of pH 8. Using preparations from which the surface epithelial cells had been removed, it was shown that at least a portion of the alkaline response to stimulation occurs in the oxyntic or tubular cells. The results are interpreted in view of existing models for the chemical reaction involved in gastric acid secretion.
Nerve pathways in celiac plexus of the guinea pig.
Authors: Kreulen D L , Szurszewski J H
Published: December 2017

In vitro preparations consisted of the right and left celiac, superior mesenteric and inferior mesenteric ganglia with attached extrinsic nerves, vasculature, mesentery, and colon. There were no systematic differences in membrane electrical properties (recorded intracellularly) between neurons in the different ganglia. Stimulation of associated nerve trunks produced graded synaptic responses in plexus neurons. Presynaptic fibers were found in splanchnic and mesenteric nerves. Input from celiac nerves dominated in the celiac galglia; input from the intermesenteric fibers dominated in the superior mesenteric ganglion. When the ganglia were attached to the entire colon, 33% of the neurons in the celiac and 54% in the superior mesenteric ganglion received a continuous excitatory synaptic input that was increased by distending the colon. This input was interrupted irreversibly by transsection of the mesenteric nerves. These results show that both the afferent and efferent pathways of a peripheral reflex arc are located in the mesenteric nerves and may mediate visceral reflexes between mechanoreceptors and sympathetic neurons in the colon.
Changes in pituitary and thyroid function with increasing age in young male rats.
Authors: Azizi F
Published: December 2017

As the age of young adult male rats increased from 30 to 150 days, the serum thyroxine (T4) decreased by 50% and the serum thyroid-stimulating hormone (TSH) increased by 250%. There was no change in the serum triiodothyronine (T3). The increment in serum TSH after injection of thyrotropin-releasing hormone (TRH) was not significantly different at any of the ages studied, but the old animals had significantly lower increments in serum T4 and T3 after subcutaneous administration of bovine TSH. Despite a higher basal serum TSH, the older rats had a lesser increase in serum TSH after thyroidectomy or propylthiouracil. Thus, 1) there is a progressive decline in intrinsic thyroid function between 30 and 150 days of age in male rats, and 2) pituitary TSH response to fall in serum concentration of thyroid hormones is also decreased with age.
Mucosal gastrin receptor. I. Assay standardization and fulfillment of receptor criteria.
Authors: Takeuchi K , Speir G R , Johnson L R
Published: December 2017

Using iodinated gastrin with demonstrable biological activity, this study has shown that optimal specific gastrin binding occurs in rat gastric mucosal 270--30,000 g membrane preparations after an incubation period of 30 min at 30 degrees C (pH 7.4) with a protein concentration of 150--200 micrograms per assay tube. The gastrin binding was shown to be saturable with an equilibrium Ka of approximately 0.25 X 10(10) M-1 and an equilibrium Kd of approximately 4 X 10(10) M. The binding capacity was approximately 4 fmol/mg protein. Specific gastrin binding was shown to be present in the oxyntic gland and duodenal mucosa and to be absent from the antral mucosa, liver, spleen, and kidney. In order to decrease the specific binding of gastrin by 50% the competitors in order of potency are 15-Leu G-17 greater than cholecystokinin greater than caerulein greater than pentagastrin; secretin did not display a response similar to the other four competitors tested, indicating that its inhibition may be non-competitive. Fasting decreased the binding capacity of the gastrin receptor and refeeding brought the receptor levels back to control range; this result parallels the decrease seen in serum gastrin after fasting and the return to normal levels with refeeding. This suggests that rat gastric mucosal gastrin receptors may exhibit autoregulation. This study is the first to meet all the criteria for establishing the existence of a mucosal gastrin receptor.
Free fatty acid oxidation in bovine muscle in vivo: effects of cold exposure and feeding.
Authors: Bell A W , Thompson G E
Published: December 2017

A mixture of (1-14C)-labeled free fatty acids (FFA), complexed in bovine plasma, was infused into the abdominal aorta of conscious young steers exposed to thermoneutral or moderately cold conditions for several hours and fed 6 or 22 h before the experiment. The uptake, release, and oxidation of FFA in one hindlimb was calculated from simultaneous measurements of leg blood flow and arteriovenous difference in the specific activities of plasma 14C-FFA and blood 14CO2. Despite an invariable net release of FFA from the resting leg, uptake of 14C-FFA was considerable; of this only 14 and 3% was immediately converted to 14CO2 in fasted and fed steers, respectively. During cold exposure, increases in whole-body oxygen consumption (VO2), arterial concentration and turnover rate of plasma FFA, and a decrease in respiratory quotient were accompanied by much greater increases in VO2, uptake, and oxidation of FFA by the shivering leg. Even so, most FFA taken up were apparently not immediately oxidized to CO2, and possible alternatives for FFA metabolism in shivering muscle are discussed.
Transport and metabolism of fructose in fat cells of normal and hypophysectomized rats.
Authors: Schoenle E , Zapf J , Froesch E R
Published: December 2017

We have shown earlier that the glucose carrier of fat cells of hypophysectomized rats operates at maximal speed in the basal state and that these cells are insensitive to insulin. Here we characterize fructose transport and metabolism in adipocytes of normal and hypophysectomized rats. 3-O-methylglucose inhibits insulin-stimulated incorporation of [U-14C]fructose into fat cells and has no significant effect on basal fructose metabolism. In contrast, 2-deoxyglucose inhibits both basal and insulin-stimulated fructose incorporation. Insulin enhances fructose incorporation in normal adipocytes only in the absence of 3-O-methylglucose. In hypophysectomized rats, incorporation of glucose and of fructose is decreased and insensitive to insulin. In contrast to the glucose carrier, the specific fructose carrier appears to be insensitive to insulin and to continue to operate with unchanged characteristics after hypophysectomy. Thus, hypophysectomy leads to a specific alteration of the insulin-sensitive glucose carrier, whereas the insulin-insensitive fructose carrier remains unaltered.
Comparison of proximal and distal colonic muscle of the rabbit.
Authors: Tucker H J , Snape W J , Cohen S
Published: December 2017

Mechanical length-tension properties and response to neurohumoral agents were compared for proximal and distal colonic muscle. Resting tension during stretch, acetylcholine-stimulated tension, and the total tension were determined. Proximal circular muscle developed a maximum total tension of 0.96 +/- 0.18 kg/cm2 (mean +/- SE) compared to 0.86 +/- 0.06 kg/cm2 for the distal colon (P greater than 0.05). Resting tension was 0.33 +/- 0.03 kg/cm2 for the proximal colon and 0.05 +/- 0.01 kg/cm2 for the distal colon at the length of optimal acetylcholine-stimulated tension (Lo) (P less than 0.01). Longitudinal muscle showed a similar difference for the proximal and distal colon. The high resting tension in the proximal colonic muscle was reduced by nitroprusside or calcium-free Krebs with EGTA. Dose-response curves to acetylcholine, histamine, phenylephrine, and isoproterenol were similar for the muscle of either part of the colon. Gastrin or cholecystokinin had no effect on the muscle. In summary, the circular or longitudinal muscles of the proximal and distal colon have different length-tension properties but only minimal differences in response to neurohumoral agents.
Quantitative comparison of pathways of hepatic glycogen repletion in fed and fasted humans.
Authors: Shulman G I , Cline G , Schumann W C , Chandramouli V , Kumaran K , Landau B R
Published: December 2017

The effect of fasting vs. refeeding on hepatic glycogen repletion by the direct pathway, i.e., glucose----glucose 6-phosphate (G-6-P)----glycogen, was determined. Acetaminophen was administered during an infusion of glucose labeled with [1-13C]- and [6-14C]glucose into four healthy volunteers after an overnight fast and into the same subjects 4 h after breakfast. 13C enrichments in C-1 and C-6 of glucose formed from urinary acetaminophen glucuronide compared with enrichments in C-1 and C-6 of plasma glucose provided an estimate of glycogen formation by the direct pathway. The specific activity of glucose from the glucuronide compared with the specific activity of the plasma glucose, along with the percentages of 14C in C-1 and C-6 of the glucose from the glucuronide, also provided an estimate of the amount of glycogen formed by the direct pathway. The estimates were similar. Those from [6-14C]glucose would have been higher than from [1-13C]glucose if the pentose cycle contribution to overall glucose utilization had been significant. After an overnight fast, during the last hour of infusion, 49 +/- 3% of the glycogen formed was formed via the direct pathway. After breakfast, at similar plasma glucose and insulin concentrations, the percentage increased to 69 +/- 7% (P less than 0.02). Thus the contributions of the pathways to hepatic glycogen formation depend on the dietary state of the individual. For a dietary regimen in which individuals consume multiple meals per day containing at least a moderate amount of carbohydrates most glycogen synthesis occurs by the direct pathway.
Adrenalectomy increases brown adipose tissue metabolism in ob/ob mice housed at 35 degrees C.
Authors: Kim H K , Romsos D R
Published: December 2017

Adrenalectomy arrests the development of obesity in ob/ob mice fed a high-starch diet and housed at a normal room temperature (20-25 degrees C) partly by stimulating the low thermogenic activity of brown adipose tissue (BAT). The present study was undertaken to determine if adrenalectomy would also lower energy retention and stimulate BAT metabolism in ob/ob mice housed in a warm environment (35 degrees C) where BAT thermoregulatory heat production is not needed. Adrenalectomy prevented hyperphagia and hyperinsulinemia and lowered the efficiency of energy retention in ob/ob mice housed at 35 degrees C, which is comparable to results obtained at 20-25 degrees C. Sympathetic nervous system stimulation of BAT (interscapular and subscapular depots) assessed by norepinephrine turnover was increased in adrenalectomized ob/ob mice. Thermogenic activity of BAT in adrenalectomized ob/ob mice (as assessed by GDP binding to isolated BAT mitochondria, GDP-inhibitable acetate-induced BAT mitochondrial swelling, and Mg2(/)-activated GDP binding to BAT mitochondria) was not elevated when results were expressed per milligram of mitochondrial protein but was elevated approximately 65% when expressed per interscapular and subscapular depots because adrenalectomy increased BAT mitochondrial mass. Adrenalectomy lowers the efficiency of energy retention and stimulates BAT metabolism even when ob/ob mice are housed in a warm environment.
Adrenal steroid receptor binding in spleen and thymus after stress or dexamethasone.
Authors: Miller A H , Spencer R L , Stein M , McEwen B S
Published: December 2017

Type I and II adrenal steroid receptor binding was measured in spleen and thymus of adrenalectomized (ADX) rats and intact rats at basal levels of corticosterone after 1 h of restraint stress or after exogenous administration of dexamethasone (DEX). Concurrent receptor determinations were made in the hippocampus and pituitary. Receptor binding measures in immune tissues and pituitary were less responsive to varying levels of endogenous hormones than binding measures in hippocampus. Compared with ADX rats, type I binding in spleen and pituitary of intact rats at basal levels of corticosterone was unchanged, whereas type I binding in the hippocampus was significantly decreased. Furthermore, despite peak levels of corticosterone, type II binding in spleen, thymus, and pituitary of stressed rats was also unchanged, whereas type II binding in the hippocampus of stressed animals was significantly lower. In contrast, DEX, a well-known immunosuppressant, reduced type II binding in immune tissues more than in the hippocampus. Because a decrease in receptor binding measured in vitro may reflect receptor activation in vivo, these results suggest that there may be considerable heterogeneity in the degree of activation of adrenal steroid receptor subtypes in immune, pituitary, and hippocampal tissue by endogenous and exogenous glucocorticoids.
Renal arginine synthesis: studies in vitro and in vivo.
Authors: Dhanakoti S N , Brosnan J T , Herzberg G R , Brosnan M E
Published: December 2017

Renal arginine synthesis is a major endogenous source of arginine. Argininosuccinate lyase occurs almost exclusively in kidney cortex. In studies with isolated renal cortical tubules, we observed rapid rates of arginine synthesis from citrulline, provided a source of the N atom of the guanidino group of arginine was supplied. Aspartate, glutamate, or glutamine were effective, whereas glycine, alanine, serine, or NH4Cl were ineffective as this second substrate. Arginine synthesis as a function of citrulline concentration was determined and was found to be highly sensitive to citrulline concentrations in the physiological range (60 microM), suggesting that renal arginine synthesis in vivo could be regulated by circulating citrulline levels. Therefore, arginine synthesis by the kidney was investigated in vivo by measuring the net flux of citrulline and arginine in saline-infused (control group) and citrulline-infused rats. In normal animals, uptake of citrulline was 60.5 +/- 20.7 nmol.min-1.100 g body wt-1, and a similar arginine release was observed. Citrulline infusion that increased circulating citrulline levels fourfold resulted in a similar increase in renal citrulline uptake (224 +/- 33 nmol.min-1.100 g-1) and a similar increase in renal production of arginine. The results suggest that the availability of citrulline is a limiting factor for renal arginine synthesis in rats.
Effect of bathocuproine disulfonate, a copper chelator, on cyst(e)ine metabolism by freshly isolated rat hepatocytes.
Authors: Coloso R M , Drake M R , Stipanuk M H
Published: December 2017

The metabolism of L-cysteine was studied in freshly isolated rat hepatocytes. Because cysteine is rapidly oxidized in oxygenated incubation medium at neutral pH, the effect of bathocuproine disulfonate, a copper-specific chelator, was investigated. Addition of bathocuproine disulfonate resulted in a higher extracellular cysteine-to-half-cystine ratio in incubations of hepatocytes with cysteine. Bathocuproine disulfonate also increased the total uptake and metabolism of cysteine plus cystine [cyst(e)ine] by hepatocytes, which is consistent with the more efficient transport of cysteine than of cystine by freshly isolated rat hepatocytes. The partitioning of cysteine between cysteinesulfinate-dependent and cysteinesulfinate-independent pathways of catabolism was also altered by the addition of bathocuproine disulfonate; the percentage of total catabolic flux that resulted in taurine plus hypotaurine formation was greater, and the percentage of total catabolic flux that occurred by the beta-cleavage of cystine in a reaction catalyzed by gamma-cystathionase was less in incubations that contained bathocuproine disulfonate. Thus addition of bathocuproine disulfonate to maintain a higher extracellular thiol-to-disulfide ratio favored cysteinesulfinate-dependent catabolism of cysteine in rat hepatocytes.
Effects of amylin on glucose metabolism and glycogenolysis in vivo and in vitro.
Authors: Young D A , Deems R O , Deacon R W , McIntosh R H , Foley J E
Published: December 2017

The effects of amylin on glucose metabolism and glycogenolysis were examined in vivo and in vitro. Eighteen-hour-fasted rats were infused with 5 nmol.kg-1.min-1 amylin and [3-3H]glucose for 120 min. Blood glucose levels increased an average of 45% during the infusion. Glucose turnover measurements indicated that the overall rate of glucose appearance (Ra) did not change, but the metabolic clearance rate of glucose was decreased by 42%. Samples of liver, gastrocnemius, and soleus muscles were freeze-clamped at the end of the infusion period and analyzed for glycogen and glucose 6-phosphate levels. Glycogen levels were decreased in all tissue samples, whereas glucose 6-phosphate was elevated in gastrocnemius and soleus muscles. Isolated soleus muscles were incubated in vitro with 200 microU/ml of insulin and 1, 10, or 100 nM amylin. Amylin treatment had no effect on 3-O-methyl-D-glucose transport; however, 2-deoxy-D-glucose uptake was inhibited by 33 or 48% at 10 or 100 nM amylin, respectively. Glycogen levels were also decreased after treatment with 10 and 100 nM amylin. Glucose 6-phosphate levels were not affected by amylin treatment in the presence of insulin but were increased nearly twofold in its absence. The data suggest that amylin stimulates glycogenolysis and inhibits glucose uptake both in vivo and in vitro and that the inhibition of glucose uptake is due to inhibition of glucose phosphorylation (i.e., hexokinase).
Effects of high levels of fatty acids on functional recovery of ischemic hearts from diabetic rats
Authors: Lopaschuk G. D. , Saddik M. , Barr R. , Huang L. , Barker C. C. , Muzyka R. A.
Published: December 2017

In this study we determined the effects of high levels of fatty acids on recovery of heart function when present either during or after ischemia. Isolated working hearts from 6-wk streptozotocin diabetic and control rats perfused with 11 mM glucose were subjected to 25 min of global ischemia followed by 30 min of aerobic reperfusion. Four groups were studied: 1) 1.2 mM palmitate present before, during, and after ischemia; 2) 1.2 mM palmitate present before and during ischemia, followed by reperfusion in the absence of palmitate; 3) no palmitate before and during ischemia, followed by 1.2 mM palmitate during reperfusion; and 4) no palmitate before and during ischemia or during reperfusion. In control hearts, palmitate during reperfusion depressed recovery of function regardless of whether palmitate was present or absent during ischemia. In contrast, palmitate present during reperfusion did not depress recovery of mechanical function in the diabetic rat hearts. However, the presence of palmitate during ischemia itself in diabetic rat hearts was detrimental to recovery of mechanical function. The presence of palmitate during ischemia resulted in an accelerated rate of ATP loss and a decreased rate of lactate accumulation during ischemia, although this effect was similar in control and diabetic rat hearts. Our results demonstrate that high concentrations of fatty acids depress functional recovery of control rat hearts during the reperfusion period but depress recovery of function in diabetic rat hearts when present during ischemia itself.
Production of parathyroid hormone-related protein by the rat mammary gland in pregnancy and lactation
Authors: Rakopoulos M. , Vargas S. J. , Gillespie M. T. , Ho P. W. , Diefenbach-Jagger H. , Leaver D. D. , Grill V. , Moseley J. M. , Danks J. A. , Martin T. J.
Published: December 2017

Production of parathyroid hormone-related protein by the rat mammary gland in pregnancy and lactation. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E1077-E1085, 1992.--Production of parathyroid hormone-related protein (PTHrP) by the mammary gland of Sprague-Dawley rats has been examined using immunohistochemistry and in situ hybridization to detect PTHrP and PTHrP mRNA, respectively. PTHrP and PTHrP mRNA could be demonstrated in nests of epithelial cells of the developing mammary gland at day 14 of pregnancy and in the epithelial secretory cells lining the alveoli during the latter stages of pregnancy and during lactation. A specific radioimmunoassay was also used to measure the concentration of PTHrP secreted in the milk throughout lactation. The concentration of PTHrP in milk was relatively low initially but increased during the latter stages of lactation, whereas calcium concentrations remained virtually constant throughout lactation. No correlation was found between the concentrations of calcium and PTHrP in rat milk. These results show that PTHrP is present in rat milk and also in mammary tissue before parturition, and therefore it may assist in the development of the mammary gland during pregnancy.
Dose-dependent effects of aluminum on osteocalcin synthesis in osteoblast-like ROS 17/2 cells in culture
Authors: Fanti P. , Kindy M. S. , Mohapatra S. , Klein J. , Colombo G. , Malluche H. H.
Published: December 2017

This in vitro study evaluates the effect of aluminum (Al3+) on osteocalcin, a small protein that is produced by the osteoblast. After stimulation with various doses of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; 10(-11) to 10(-9) M], osteocalcin was consistently lower in the culture medium of ROS 17/2 osteoblastic cells conditioned with 5 microM Al(3+)-saturated transferrin (AlTR) than in apotransferrin (ApoTR)-treated controls. In a second experiment, cultures were conditioned with various doses of AlTR or ApoTR (1.6-8.0 microM) and stimulated with 10(-9) M 1,25(OH)2D3. High doses of AlTR (4.8-8.0 microM) resulted in lower medium and unchanged intracellular content of osteocalcin than treatment with equal amounts of ApoTR. However, in the same experiment, lower doses of AlTR or ApoTR (1.6 and 3.2 microM) yielded different results, i.e., increased medium and intracellular contents of osteocalcin in the Al(3+)-treated cells. Expression of osteocalcin mRNA was not altered in cultures conditioned with low (1.6 microM) or high (8.0 microM) concentrations of AlTR or ApoTR. Similarly, no effect of Al3+ was observed on total protein content, the rate of total protein synthesis, and the degradation of secreted osteocalcin in cultures conditioned with various doses of AlTR or ApoTR. These findings suggest that AlTR affects osteocalcin synthesis in a specific manner, without concomitant effects on the rate of total protein synthesis or on the rate of degradation of osteocalcin. This effect is dose dependent, i.e., low doses of AlTR stimulate and high doses suppress osteocalcin synthesis and/or secretion, and it appears to be posttranscriptional, since the expression of osteocalcin mRNA is not affected.
Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone
Authors: Gomez-Sanchez E. P. , Gomez-Sanchez C. E.
Published: December 2017

The apparent mineralocorticoid excess syndrome of patients ingesting large amounts of licorice or its derivatives is thought to be caused by the antagonism by these compounds of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). 11 beta-HSD inactivates cortisol and corticosterone, allowing the more abundantly produced glucocorticoids access to the mineralocorticoid receptor (MR) in the kidney, where they act as mineralocorticoids. We have found that the infusion of both glycyrrhizic acid, an active principle of licorice, and carbenoxolone, a synthetic analogue, into a lateral ventricle of the brain [intracerebroventricular (icv)] of a rat, at a dose less than that which has an effect when infused subcutaneously, produces hypertension. Furthermore, the hypertension produced by the oral administration of carbenoxolone or glycyrrhizic acid is blocked by the icv administration of RU 28318, an MR antagonist, at a dose below that which has an effect on blood pressure when infused subcutaneously. While the oral administration caused saline polydipsia and polyuria typical of chronic systemic mineralocorticoid excess, the icv licorice derivatives produced hypertension without affecting saline appetite. Sensitizing the rats to mineralocorticoid hypertension by renal mass reduction and increasing salt consumption was not necessary for the production of hypertension. These findings provide additional evidence for a central role in blood pressure control by mineralocorticoids that is distinct from their renal effects. They also suggest that more is involved in licorice-induced hypertension than only inhibition of 11 beta-HSD.
Hyperglycemic athymic nude mice: factors affecting in vitro insulin secretion
Authors: Zeidler A. , Edwards P. , Goldman J. , Kort S. , Meehan W. P. , Levin S. R.
Published: December 2017

The strain of athymic nude male mice (ANM) developed at the University of Southern California (USC) exhibits spontaneous hyperglycemia and relative hypoinsulinemia in vivo. To investigate factors that influence insulin secretion in this animal model of non-insulin-dependent diabetes mellitus, we utilized the isolated perfused mouse pancreas of the ANM-USC and control BALB/c mice. We compared in vitro glucose-induced insulin secretion in ANM-USC and control mice, inhibition of secretion by somatostatin, and variability of insulin secretion over the two-year period it took to complete these experiments. Glucose-induced insulin secretion from the isolated pancreas was biphasic in both ANM-USC and controls. Insulin secretion was quantitatively equal to or greater than control mice, depending on the phase of secretion analyzed and the source of the control mice. In contrast to pancreases of control mice, insulin secretion from ANM-USC pancreases was relatively resistant to inhibition of insulin secretion by somatostatin. Variability in insulin secretion over the two years in which these experiments were performed was greater from pancreases of control than that observed from pancreases of the ANM-USC. The hyperglycemic ANM-USC mouse does not demonstrate diminished insulin secretion in vitro yet is relatively hypoinsulinemic in vivo. Thus circulating factors other than somatostatin might contribute to the insulinopenic stage in this animal model.
Exercise interrupts ongoing glucocorticoid-induced muscle atrophy and glutamine synthetase induction
Authors: Falduto M. T. , Young A. P. , Hickson R. C.
Published: December 2017

This study was undertaken to determine whether regular endurance exercise is a deterrent to a developing state of muscle atrophy from glucocorticoids and to evaluate whether the contractile activity antagonizes the hormonal actions on glutamine synthetase, alanine aminotransferase, and cytosolic aspartate aminotransferase (cAspAT). Adult female rats were administered cortisol acetate (CA, 100 mg/kg body wt) or an equal volume of the vehicle solution for up to 15 days. Exercise (treadmill running at 31 m/min, 10% grade, 90 min/day) was introduced after 4 days of CA treatment, at which time plantaris and quadriceps muscle mass had been reduced to 90% of control levels. Running for 11 consecutive days prevented 40 mg of the 90-mg loss and 227 mg of the 808-mg loss that were subsequently observed in plantaris and quadriceps muscles, respectively, in the sedentary animals. Glutamine synthetase mRNA and enzyme activity were elevated threefold by glucocorticoid treatment in the deep quadriceps (fast-twitch red) muscles after 4 days. Initiating exercise completely interfered with the further hormonal induction (to approximately 5-fold) of this enzyme and, after 11 consecutive days of the exercise regimen, glutamine synthetase mRNA and enzyme activity were 58 and 68% of values from CA-treated sedentary animals. In vehicle-treated groups, basal levels of glutamine synthetase expression were also diminished by exercise to approximately 40% of the values in sedentary controls. Hormone treatment did not alter either aminotransferase enzyme activity but reduced cAspAT mRNA in fast-twitch red muscles by 50%. Exercise abolished the glucocorticoid effect on cAspAT mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanisms of repetitive retrograde contractions in response to sustained esophageal distension: a study evaluating patients with postfundoplication dysphagia
Authors: Carlson Dustin A. , Kahrilas Peter J. , Ritter Katherine , Lin Zhiyue , Pandolfino John E.
Published: December 2017

Repetitive retrograde contractions (RRCs) in response to sustained esophageal distension are a distinct contractility pattern observed with functional luminal imaging probe (FLIP) panometry that are common in type III (spastic) achalasia. RRCs are hypothesized to be indicative of either impaired inhibitory innervation or esophageal outflow obstruction. We aimed to apply FLIP panometry to patients with postfundoplication dysphagia (a model of esophageal obstruction) to explore mechanisms behind RRCs. Adult patients with dysphagia after Nissen fundoplication ( n = 32) or type III achalasia ( n = 25) were evaluated with high-resolution manometry (HRM) and upper endoscopy with FLIP. HRM studies were assessed for outflow obstruction and spastic features: premature contractility, hypercontractility, and impaired deglutitive inhibition during multiple-rapid swallows. FLIP studies were analyzed to determine the esophagogastric junction (EGJ)-distensibility index and contractility pattern, including RRCs. Barium esophagram was evaluated when available. RRCs were present in 8/32 (25%) fundoplication and 19/25 (76%) achalasia patients ( P < 0.001). EGJ outflow obstruction was detected in 21 (67%) fundoplication patients by HRM, FLIP, or esophagram [6 (29%) had RRCs]. On HRM, none of the fundoplication patients had premature contractility, whereas 3/4 with defective inhibition on multiple-rapid swallows and 2/4 with hypercontractility had RRCs. Regression analysis demonstrated HRM with spastic features, but not esophageal outflow obstruction, as a predictor for RRCs. RRCs in response to sustained esophageal distension appear to be a manifestation of spastic esophageal motility. Although future study to further clarify the significance of RRCs is needed, RRCs on FLIP panometry should prompt evaluation for a major motor disorder.

NEW & NOTEWORTHY Repetitive retrograde contractions (RRCs) are a common response to sustained esophageal distension among spastic achalasia patients when evaluated with the functional luminal imaging probe. We evaluated patients with postfundoplication dysphagia, i.e., patients with suspected mechanical obstruction, and found that RRCs occasionally occurred among postfundoplication patients, but often in association with manometric features of esophageal neuromuscular imbalance. Thus, RRCs appear to be a manifestation of spastic esophageal dysmotility, likely from neural imbalance resulting in excess excitation.
Instantaneous changes of alpha-adrenoceptor affinity caused by moderate cooling in canine cutaneous veins
Authors: Janssens W. J. , Vanhoutte P. M.
Published: December 2017

Experiments were performed to investigate why cooling augments the contractile responses of superficial veins, but depresses that of deep limb veins. Rings of dog's saphenous veins were mounted in an organ chamber for isometric tension recording. Cooling (from 37 to 24 degrees C) depressed the tissular uptake of [3H]norepinephrine and potentiated the contraction caused by norepinephrine and sympathetic nerve stimulation; this potentiation persisted after inhibition of the disposition mechanisms for the catecholamine and in the presence of ouabain or iproveratril. The affinity of the alpha adrenoceptors, to judge from the KA values for norepinephrine and from the pA2 values for the competitive antagonist phentolamine, was significantly greater at 24 degrees C than at 37 degrees C. Thus, an instantaneous change in the affinity of alpha adrenoceptors explains the augmented response of the cutaneous veins to adrenergic stimulation. By contrast, cooling depressed the response of femoral veins to norepinephrine and did not significantly affect the affinity of alpha adrenoceptors in this preparation, indicating that the temperature sensitivity of alpha adrenoceptors in cutaneous veins is related to chronic exposure to variations in local temperature.
Extent of utilization of the Frank-Starling mechanism in conscious dogs
Authors: Boettcher D. H. , Vatner S. F. , Heyndrickx G. R. , Braunwald E.
Published: December 2017

The extent to which an increase in preload increases left ventricular (LV) end-diastolic (ED) diameter (D) was studied in seven conscious dogs instrumented with ultrasonic D transducers and miniature LV pressure (P) gauges. Preload was elevated by three techniques: 1) volume loading with saline infusion, 2) induction of global myocardial ischemia by constricting the left main coronary artery, and 3) infusion of methoxamine. These three interventions increased LVEDP to over 30 mmHg from a control of 10 +/- 1 mmHg. With volume loading, LVEDD rose by only 1.55 +/- 0.39 mm from a control of 44.08 +/- 1.08 mm; with ischemia LVEDD rose by only .96 +/- .29 mm from a control of 42.55 +/- 2.18 mm, while with methoxamine LVEDD rose by only 1.34 +/- 0.38 mm from a control of 43.89 +/- 2.07 mm. In contrast, in the open-chest, anesthetized dog, LVEDD was greatly reduced and volume expansion resulted in a profound increase in LVEDD. Thus, the Frank-Starling mechanism is not an important controlling mechanism in the normal, reclining, conscious animal, since LVEDD appears to be near maximal at rest and does not increase substantially despite striking increases in LVEDP.
Comparison of left ventricular free wall and septal diastolic compliance in the dog
Authors: Kent R. S. , Carew T. E. , LeWinter M. M. , Covell J. W.
Published: December 2017

Septal to free wall dimensions are frequently employed for the analysis of diastolic compliance. However, the diastolic properties of these anatomically distinct regions of left ventricle are not well characterized. Regional compliance was studied in eight open-chest anesthetized dogs. Pairs of 2-mm-diameter piezoelectric crystals were implanted in the left ventricular free wall or septum 1.38 +/- 0.06 cm apart at a midwall location 58% +/- 1.9 of the left ventricular endocardial-epicardial or left ventricular endocardial-right ventricular endocardial distance. Left ventricular end-diastolic pressure was increased from an average of 8.1-21.0 mmHg, with a resulting average maximum end-diastolic strain of 11% (end-diastolic (ED) segment length/control ED length). Regional stiffness was assessed at all sites based on the relationship between left ventricular end-diastolic pressure and regional strain. Neither strain nor calculated stiffness coefficients differed significantly among the three sites. Septal transmural pressure (left ventricular end-diastolic pressure--right ventricular end-diastolic pressure) was nearly constant as left ventricular end-diastolic pressure increased during volume infusion and thus did not account for the observed septal strain.
Gonadal hormones and pathogenesis of occlusive arterial thrombosis
Authors: Uzunova A. D. , Ramey E. R. , Ramwell P. W.
Published: December 2017

Arterial thrombus formation was induced in male and female Wistar rats (3 mo) by inserting a loop-shaped polyethylene cannula into the abdominal aorta. Thrombogenesis was also induced in mature male and female New Zealand rabbits by constriction of the femoral artery and injection of ellagic acid. The criteria for thrombus development in the cannulated rats were: incidence of thrombosis (IT), obstruction time (OT), and thrombus weight (TW). We observed a significant sex difference in all these criteria of thrombogenesis in both rats and rabbits. Pretreatment of either sex with Depo-testosterone shortened OT, increased TW about fivefold in males and threefold in females, and increased mortality rate (MR) more than fourfold in both sexes. Prolonged pretreatment with Depo-testosterone increased in all aspects of thrombogenesis. Depo-estradiol had marginal ameliorating effects in male rats only. Both the antiandrogen Flutamide, and aspirin, significantly decreased the thrombogenic effects of testosterone. Thus, testosterone may be a significant risk factor in experimentally induced thrombogenesis in rats and rabbits.
Comparison of SA nodal and subsidiary atrial pacemaker function and location in the dog
Authors: Jones S. B. , Euler D. E. , Hardie E. , Randall W. C. , Brynjolfsson G.
Published: December 2017

A 3-4 cm length of sulcus terminalis tissue including the sinoatrial node (SAN) was excised from 14 dogs. After an initial junctional rhythm with SAN excision a P wave emerged within days to weeks in 12 animals. Maximum heart rates of the SAN (preoperative) in response to exercise (276 +/- 15 beats/min), isoproterenol infusion in conscious animals (272 +/- 11 beats/min), and stellate stimulation during anesthesia (273 +/- 9 beats/min) were significantly greater than subsidiary pacemakers (postoperatively) for exercise (219 +/- 9 beats/min), isoproterenol (226 +/- 8 beats/min), and stellate stimulation (197 +/- 9 beats/min). During a final experiment, electrophysiological mapping of the area of earliest epicardial activation (pacemaker location) was carried out. By use of a suction electrode in reference to plunge electrodes located in the anterior interatrial band (AIB), eustachian ridge of the coronary sinus, and limbus of the fossa ovalis, the pacemaker was located at the inferior vena cava-inferior right atrial junction in 80% of the animals mapped. During isoproterenol infusion the foci shifted to regions of the AIB in 70% of the animals mapped. The concept of pacemaker hierarchy is discussed.
Quantitation of collateral and ischemic flows with microspheres and diffusible indicator
Authors: Cohen M. V.
Published: December 2017

Flow to myocardium following coronary occlusion may not originate solely from collateral channels. Some flow might be derived from overlapping coronary arteries which also perfuse tissue within the territory of the obstructed vessel prior to occlusion. Left atrial microsphere injection during perfusion of the left anterior descending (LAD) artery from a special reservoir containing microsphere-free blood and again after LAD occlusion permitted measurement of noncollateral overlap and total ischemic LAD (TIF) flows, respectively, and mathematical derivation of true collateral flow (TCF). Whereas TIF averaged 0.25 +/- 0.03 ml/min per g, TCF was 0.14 +/- 0.03 ml/min per g, only 50.6% of TIF. The remainder of the TIF represented either inadvertant inclusion of normally perfused tissue with the ischemic LAD myocardium or actual overlap of LAD and left circumflex circulations. 86RbCl was injected simultaneously with the microspheres following coronary occlusion. 86Rb and microsphere densities in the whole heart and ischemic area were closely correlated, although microsphere distribution tended to be more heterogeneous. No segment of ischemic myocardium containing 86Rb was free of microspheres. Therefore, the geometry of undeveloped collateral channels is adequate to permit passage of 15-micron particles. Absolute 86Rb flows were consistently less than microsphere flows.
Regional variation of series elasticity in canine arterial smooth muscles
Authors: Cox R. H.
Published: December 2017

Segments of carotid, iliac, renal, mesenteric, coronary, and internal thoracic arteries were studied in vitro to correlate the mechanical properties of series (SE) and parallel (PE) elastic elements with connective tissue (CT) composition and with active responses to potassium activation. The PE properties were determined using pressure-diameter data with passive smooth muscle (SM). SE properties were determined from periodic incremental releases imposed during isometric responses to [K+]O at a diameter corresponding to Lmax, the optimum muscle length. Active stress responses and diameter responses were determined using pressure-diameter data for active and passive conditions. Collagen and elastin contents were determined for each sample. No correlation was found between CT content and PE or SE properties for the various sites. A close correlation was found to exist between SE and PE properties at each site, i.e., the sites with the stiffest PE also had the stiffest SE. SM, with stiffer SE, had a larger diameter response with the same active stress response and the same diameter response with a smaller active stress response, compared to SM with more compliant SE. This suggests that passive properties of SM can have a significant influence on the external manifestations of contractile element properties.
Depression of regional blood flow and wall thickening after brief coronary occlusions
Authors: Heyndrickx G. R. , Baig H. , Nellens P. , Leusen I. , Fishbein M. C. , Vatner S. F.
Published: December 2017

The effects of a 15-min coronary occlusion and subsequent reperfusion were investigated in conscious dogs previously instrumented for measurement of left ventricular pressure, dP/dt, regional wall thickening, electrograms, and myocardial blood flow. Coronary occlussion reduced overall left ventricular function only slightly but eliminated systolic wall thickening in the ischemic zone and reduced regional myocardial blood flow in the ischemic zone from 1.04 +/- 0.04 to 0.27 +/- 0.02 ml/min per g and the endo/epi flow ratio from 1.23 +/- 0.04 to 0.44 +/- 0.04, while S-T segment elevation increased from 1.1 +/- 0.3 to 8.2 +/- 0.9 mV. After release of the occlusion, S-T segment elevation disappeared within 1 min while reactive hyperemia in the previously occluded artery and a transient increase in cardiac diastolic wall thickness occurred and then subsided by 15 min. In contrast, systolic wall thickening and the endo/epi flow ratio remained significantly depressed for more than 3 h. Thus reperfusion after a 15 minute coronary occlusion results in a prolonged period of reduced regional myocardial blood flow, particularly in the endocardial layers, which correlates with the prolonged depression of regional myocardial shortening and wall thickening.
Hyperresponsivitiy of spontaneously hypertensive rat to indirect measurement of blood pressure
Authors: Chiueh C. C. , Kopin I. J.
Published: December 2017

A chronic, indwelling, tail arterial cannula was implated in conscious undisturbed rats for measurement of blood pressure and heart rate and for obtaining blood samples. As an index of sympathetic activity, plasma levels of catecholamines in arterial blood of conscious animals were assayed by a radioenzymatic, paper-chromatographic procedure. Blood pressures of unrestrained spontaneously hypertensive (SHR) rats in their home cages (161 +/- 3/141 +/- 4 mmHg) were not different from those of pentobarbitol-anesthetized, hypertensive animals but were about 25 mmHg lower than awake animals during the restraint required for the tail-cuff procedure. Basal levels of plasma catecholamines in awake, undisturbed or in pentobarbital-anesthetized animals were similar in age-matched SHR and normotensive Wistar-Kyoto (WKY) rats. SHR rats were shown to have greater increase in plasma catecholamines than WKY rats during forced immobilization or restraint for indirect measurement of blood pressure.
Shear stress and aortic histamine synthesis
Authors: DeForrest J. M. , Hollis T. M.
Published: December 2017

Aortic histamine-forming capacity (HFC) has been examined in relationship to the applied mean shear stress intensity created by pulsatile perfusion of rabbit aortas with platelet-free blood for a 1-h period. Mean shear stress intensities ranged from 22 to 109 dyn/cm2. Results indicate that a high correlation exists between the shear stress and the HFC which is described by the regression equation y = 0.28 x -6.1, where y = HFC and x = mean shear stress intensity. Results suggest that the rate of histamine formation is sensitive to the applied shear stress, and that the histidine decarboxylase system of the aorta may have the potential of serving as one coupling agent between applied hemodynamic stress and resultant alterations in aortic wall resistance to macromolecules.
Motility and blood flow distribution within the wall of the gastrointestinal tract
Authors: Chou C. C. , Grassmick B.
Published: December 2017

In anesthetized dogs, the effects of a gentle manipulation of the gut wall, increasing the lumen pressure to 20 mmHg by distention, or an intravenous infusion of physostigmine on blood flow distribution within the wall of the gastrointestinal tract were studied with radioactive microspheres. Manipulation and distension produced rhythmic contractions and increased flow to the distended and manipulated segments. The increased flow was confined to the muscularis serosa; the mucosa-submucosa flow was unchanged. Physostigmine produced a sustained tonic contraction and decreased flow to the whole wall of the stomach, duodenum, jejunum, ileum, and colon. The decreased flow was confined to the mucosa-submucosa; the muscularis serosa flow was unchanged. Thus, the muscularis serosa vasculatures escape the effects of a fall in vascular transmural pressure during the tonic contraction. Manipulation, distention, and physostigmine all increase the percentage of total wall flow perfusing the muscularis serosa. These studies suggest that active hyperemia, similar to exercise hyperemia in skeletal muscles, occurs in the muscularis of gut wall during intestinal contractions.