bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal sodium transport in vitamin D resistant hypophosphatemic rickets
Authors: Brunette Michèle G. , Mernissi Ghazi El , Doucet Alain
Published: April 2011

To investigate the possible role of a Na transport defect in the pathogenesis of the phosphaturia in vitamin D resistant rickets, we studied the activity of the Na–K ATPase activity along the microdissected segments of the nephron in normal (N) and hypophosphatemic mice (Hyp), the Na uptake by renal brush border membrane (BBM), as well as the interrelationship between Na and phosphate transport through this membrane. In N mice, Na-K ATPase activity was present in decreasing order, in the distal tubule, the ascending branch of the loop of Henle, the proximal tubule, and the collecting tubule. In Hyp mice, the Na–K ATPase activity was comparable to that measured in N mice, except in the granular segment of the distal tubule where a 256% of the control activity was reproducibly observed. In N mice, Na initial uptake by BBM vesicles increased with Na concentration in the incubation medium, according to two kinetic components: one saturable, evident at low substrate concentrations and the other, nonsaturable, corresponding to a passive diffusion. The addition of 5 mM PO4 in the incubation medium did not significantly influence Na transport. In contrast, Na concentration in the incubation medium largely modified the kinetics of PO4 uptake: increasing Na concentration enhanced PO4 uptake and decreased the apparent Km. In Hyp mice, Na uptake by BBM was identical to that observed in N mice, but PO4 uptake was decreased by half. Na concentration in the incubation medium similarly influenced PO4 uptake in N and Hyp mice, and the Km values at each concentration of Na were comparable in the two series of animals. It is concluded that the defect in PO4 transport in Hyp mice is not secondary to an alteration of Na transport through the BBM, nor to an abnormal relationship between Na and PO4 in the PO4 carrier system, nor to a decreased Na–K ATPase activity in the basolateral membrane of the cell. The increase in Na–K ATPase in the distal tubule is probably a secondary phenomenon, not directly related to the pathogenesis of the disease.
Effect of calcium depletion and calcium paradox on myocardial energy metabolism
Authors: Schaffer Stephen W. , Tan Boen H.
Published: April 2011

Both phases of the calcium paradox were associated with major alterations in myocardial energy metabolism. During calcium-free perfusion contractility of the heart ceased, resulting in a dramatic decrease in anaerobic and aerobic metabolism but no change in tissue high energy phosphate levels. Tissue content of most citric acid cycle intermediates were elevated, while there was a net decrease in the content of transaminase-linked amino acids. Reperfusion of the calcium-depleted heart with calcium-containing buffer failed to restore either the contractile or the metabolic state of the heart. Within seconds following calcium repletion, tissue high energy phosphate content plummeted. This occurred even though glucose utilization increased significantly and aerobic metabolism remained at levels observed in the calcium-depleted heart. Analogous to changes seen in acidosis and ischemia, α-ketoglutarate and citrate levels decreased abruptly. After a short delay, the levels of several key amino acids also dropped. The results support the hypothesis that the impairment of mitochondrial function contributes to the depletion of high energy phosphate stores during the calcium paradox.
Changes in pituitary responses to synthetic ovine corticotrophin releasing factor in fetal sheep
Authors: Norman Laurie J. , Lye Stephen J. , Wlodek Mary E. , Challis J. R. G.
Published: April 2011

The rise in cortisol in fetal sheep during late pregnancy has been related to increased responsiveness of the adrenal to ACTH. Most reports have suggested that plasma ACTH concentrations rise coincident with or after the prepartum increase in cortisol. To reexamine the relationship of cortisol with basal immunoreactive ACTH (IR-ACTH) throughout the last 40 days of pregnancy and to determine changes in fetal pituitary responsiveness during this time, we measured basal and synthetic ovine corticotrophin-releasing factor (oCRF) (10 ng – 10 μg) induced rises in ACTH and cortisol in fetal sheep at days 110–115, 125–130, and 135–140 of pregnancy. The fetuses were catheterized on day 105–120 and entered spontaneous labour at > 140 days. Basal IR-ACTH (picograms per millilitre ± SEM) rose from 16.7 ± 2.9 pg/mL at day 110–115 to 34.8 ± 8.7 pg/mL at day 141–145. There was a significant effect of time on basal ACTH concentrations with a mean increase of approximately 5 pg ACTH per millilitre of plasma per 5-day sampling interval. Plasma cortisol changed gradually between day 110 and 125 of gestation and then more rapidly to term. At day 110–115 of gestation there was no significant change in plasma ACTH after 10 or 100 ng oCRF, but there was a significant increase in ACTH after 1 μg of oCRF. Plasma cortisol did not change after any CRF injection. The change in IR-ACTH after oCRF at day 125–130 of gestation was significantly greater than that at day 110–115. Plasma cortisol concentrations were elevated following 1- and 10-μg injections of oCRF. At day 135–140, significant rises in plasma ACTH were seen in response to 1 and 10 μg oCRF, but the response was less than that at day 125–130. In contrast, the response of plasma cortisol was significantly greater than at any of the other times in gestation. We conclude the following: (i) basal ACTH concentrations rise before the major prepartum increase in plasma cortisol; (ii) pituitary responsiveness to oCRF, measured as ACTH in plasma, increases between days 110–115 and 125–130 of gestation. The ACTH response decreased at day 135–140, perhaps reflecting negative feedback control by the rising basalcortisol concentrations; (iii) adrenal responsiveness increases progressively between days 110–115 and 135–140 of gestation, as reflected by changes in the plasmacortisol concentration in response to endogenously released ACTH.
Electrophysiological effects of ethmozine in perfused rabbit hearts
Authors: Dresel Peter E. , Ogbaghebriel A. , Abraham R.
Published: April 2011

His-bundle electrocardiography was used to evaluate the effects of ethmozine on cardiac conduction in isolated perfused rabbit hearts electrically driven at cycle lengths of 320 and 250 ms. There was no significant change in conduction until high concentrations of ethmozine were reached. His-Purkinje and atrioventricular (AV) nodal conduction were slowed significantly at 0.1 μg/mL and atrial conduction at 1.0 μg/mL. Conduction block occurred at 10.0 μg/mL in all the hearts treated. Effects of the drug (0.1 and 0.01 μg/mL) on conduction of extrasystoles were also studied in hearts driven at a basic cycle length of 270 ms. No significant change was observed in atrial conduction of extrasystoles throughout the coupling intervals tested at both concentrations. Ethmozine (0.01 and 0.1 μg/mL) caused slowing of His-Purkinje conduction of extrasystoles but the effect of the drug did not change as a function of the coupling interval. An interval-dependent increase in AV-nodal conduction time was observed, with the maximum slowing of conduction occurring at coupling intervals close to the effective refractory period of the AV node. AV-nodal functional refractory period was increased significantly by ethmozine (0.01 and 0.1 μg/mL). The effective refractory period was significantly increased only at the higher concentration.
Effects of (±)-sotalol, (±)-propranolol, and (−)-propranolol on norepinephrine release upon hepatic nerve stimulation in the dog liver in vivo
Authors: Yamaguchi Nobuharu
Published: April 2011

The study was carried out to determine whether the diminished release of norepinephrine (NE) upon sympathetic activation in the presence of sotalol can be attributed to the blockade of beta-adrenoceptors in the liver. NE release from the liver was measured in hepatic venous blood collected during direct hepatic nerve stimulation in anesthetized dogs. The mean basal NE concentration in hepatic venous and aortic blood was 0.046 ± 0.003 and 0.244 ± 0.041 ng/mL, respectively. NE release increased significantly as stimulation frequency increased, while aortic NE concentration remained unchanged. The increasing response of NE release upon stimulation in the vehicle control group remained stable during the whole experimental period. In dogs treated with sotalol (5 mg/kg, i.v.), NE release was reduced approximately by 30–43%, and the difference was statistically significant (P < 0.01) at 8 Hz. (±)-Propranolol (2.5 mg/kg, i.v.) tended to diminish it, but the difference was not significant. (−)-Propranolol (0.1 mg/kg, i.v.) did not alter NE release at any frequency tested. The beta-blocking action of these drugs in the liver, as determined by the antagonism against the hepatic arterial vasodilating response to isoproterenol, was most effective with (±)-propranolol (100%), followed by (−)-propranolol (90%) and sotalol (70%). The results suggest that the inhibitory effect of sotalol on NE release may be related to a mechanism other than its beta-blocking action in the dog liver.
Influence of low extracellular Ca2+ ions on the cardiac function changes induced by verapamil in the perfused rabbit heart
Authors: Fortier Pierre A. , Bedford Gary K. , Chiong Miguel A.
Published: April 2011

We tested the hypothesis that the myocardial effects of verapamil (VER) could be enhanced by decreasing the extracellular Ca2+ concentration ([Ca2+]o) in the isolated rabbit heart at 37 °C. After perfusion with standard Krebs–bicarbonate solution containing 1.27 mM Ca2+, for a 30-min period of stabilization and 15 min of control, groups of hearts were perfused for an additional 60 min with solutions containing one of the following: 1.27 mM Ca2+ (control group), 0.23 mM Ca2+ (low [Ca2+]o group), 1.27 mM Ca2+ plus 10− M VER (VER group), or 0.23 mM Ca2+ plus 10−7 M VER (combination, CBN group). These concentrations of [Ca2+]o and VER produce submaximal responses in our preparation. We found that the heart rate – LV pressure product (RPP) in the CBN group fell rapidly to 0 in the first 2–3 min of perfusion, this response being significantly lower than in the other two groups for the first 15 min. Electromechanical dissociation (EMD) appeared in one of six hearts at 60 min and in four of six hearts at 30 min in the low [Ca2+]o and VER groups, respectively, whereas it occurred in the CBN group in all hearts at 3 min. Depolarization rate (DR) fell by 10% in the low [Ca2+]o and VER groups versus a reduction of 45% in the CBN group (P < 0.05) during the last 45 min of perfusion. The PR interval increased by 300% in the CBN group, a much greater and significant change (P < 0.05) than in the hearts exposed to VER or low [Ca2+]o. The QT interval, however, increased by 50% in the low [Ca2+]o group (P < 0.05) and decreased by 20–30% in the VER and CBN groups (P < 0.05). On the other hand there were no differences in the changes in coronary sinus flow, O2 uptake, enzyme release, or energy stores among the groups. We conclude that low [Ca2+]o enhanced the effects of VER in relation only to RPP, DR, PR interval, and possibly EMD, but had no influence on metabolism.
Tension responses of frog skeletal muscle to ramp and step length changes
Authors: Bressler Bernard H.
Published: April 2011

Tension responses to ramp shortening of varying speed in whole muscle or single fibres from the plateau of an isometric tetanus, revealed at least two distinct phases. There was a fast initial drop in tension followed by a change of slope and a definite inflexion on the tension record. As the velocity of the imposed length change was increased, the inflexion point appeared at a lower tension. Similar inflexions were not observed during ramp releases to an elastic band or a segment of semitendinosus tendon. The tension records obtained with moderately fast ramp length changes to contracting muscle reflect the T1 and T2 phases of the tension transients.
Difference in the relation between infarct and occluded bed in pentobarbital-anesthetized and conscious dogs
Authors: Jugdutt Bodh I.
Published: April 2011

The relationship between myocardial infarct size (IS) and occluded bed size (OBS) in pentobarbital-anesthetized (A, n = 16) and conscious (C, n = 20) dog models were compared. IS and OBS (postmortem coronary arteriography) were measured by computerized planimetry of weighed left ventricular (LV) rings 7 days after permanent left anterior descending (LAD, n = 19) or circumflex (LC, n = 17) coronary artery occlusion. For both A and C groups, IS was directly related to OBS (p < 0.001) and no infarcts developed for small occluded beds. For either LAD or LC subgroups, infarcts were larger in A than C dogs (49 ± 18 vs. 30 ± 19% OBS, p < 0.025), with greater slope of the linear regression between IS and OBS (p < 0.001) and less epicardial sparing on topographic mapping (p < 0.05). Although postocclusion mean arterial and left atrial pressures were similar in A and C groups, heart rates were greater in the A dogs, both pre- (125 vs. 88 beats/min, p < 0.001) and post-occlusion (151 vs. 108 beats/min, p < 0.001). Endocardial flows (radioactive microspheres) in infarct centers and margins were less in A than C dogs. Also, endocardial/epicardial (endo/epi) flow ratios in all regions were less in A than C dogs, both pre- and post-occlusion. Increasing heart rate in 10 other C dogs with LAD occlusion to that of the A group (151 beats/min) by right ventricular pacing resulted in larger infarcts with greater slope of the linear regression and less endo/epi flow ratios, as in the A group. Thus, infarcts are larger in A than C dog models. The effect appears to be related to increased myocardial oxygen demands and transmural maldistribution of flow associated with tachycardia.
Comparative spinal analgesic action of dynorphin1-8, dynorphin1-13, and a kappa-receptor agonist U50,488
Authors: Jhamandas K. , Sutak M. , Lemaire S.
Published: April 2011

The effect of intrathecal injections of dynorphin1-8 (DYN1-8), dynorphin1-13 (DYN1-13), and a putative kappa agonist, U50,488 was tested in the rat tail-flick test. DYN1-8 and DYN1-13 (5, 10, 20 μg) produced a dose-related biphasic antinociceptive response consisting of an initial and a delayed response. Injection of U50,488 (20, 40 60 μg) produced a monophasic response. The antinociceptive effect of DYN1-8 (5, 10, 20 μg) and DYN1-3 (20 μg), but not U50,488 (20 μg), was present 24 h postintrathecal injection. Pretreatment with systemic naloxone (2 mg/kg s.c.) attenuated the delayed response, but not the initial response induced by DYN1-8 and DYN1-13. The initial response was attenuated by pretreatment with intrathecal naloxone at a dose of 0.5 and 2.0 μg. The antinociceptive effect of U50,488 (20,60 μg) was not affected by pretreatment with 2.0 μg intrathecal naloxone, but was significantly reduced by 4 μg of the antagonist. Both DYN1-8 and DYN1-13 (5 μg) augmented the antinociceptive effect of intrathecally administered morphine (5, 10 μg). Intrathecal injection of DYN1-8 (5, 10, 20 μg), DYN1-13 (5 μg), and morphine (10 μg) reduced the spontaneous output of urine measured at 2 and 24 h postintrathecal injection. A similar injection of U50,488 (20 μg) had no significant action on the urinary output. The results show that long and short dynorphin fragments have a comparable activity and the spinal antinociceptive actions of dynorphin are sensitive to low doses of intrathecal naloxone. The activity profile of spinally administered dynorphins differs from that of the kappa agonist U50,488.
Adrenocortical responses to corticotropin-releasing factor in the rat
Authors: Normand Maurice , Lalonde Josée
Published: April 2011

The time course of plasma corticosterone was measured in male Sprague–Dawley rats whose endogenous release of ACTH had been blocked following rapid i.v. injections of doses ranging from 0.003 to 10 μg corticotropin-releasing factor (CRF) per rat and during i.v. infusions at rates ranging from 0.001 to 20 μg CRF∙min−1∙100 g body weight−1. The range of the dose–response curve, following rapid injection, extends from 0.01 to 0.37 μg CRF, whereas it extends over a 20 000-fold range from 0.001 to 20 ng CRF∙min−1∙100 g body weight−1 during a continuous infusion. The delayed response to a small rate of CRF could be ascribed to a relatively long time of residence of CRF in the plasma which implies that a relatively long period of time is required until a minimal plasma CRF concentration is reached after the onset of a continuous infusion of CRF at a small rate. When presented with a prolonged infusion of CRF at a large rate, the pituitary secretion of ACTH is rapidly turned on at a rate which exhibits the characteristics of a prolonged secretion at a constant large magnitude.
Nonparallel secretion of enzymes by the rabbit pancreas
Authors: Lahaie R. G. , Michel R. , Michel G. , Dagorn J. C.
Published: April 2011

Since nonparallel secretion of enzymes by the exocrine pancreas has been demonstrated with several experimental models, we were interested in verifying a recent claim that enzyme secretion remained strictly proportional (parallel) upon stimulation of the in vivo rabbit pancreas. Pancreatic juice was collected by extraduodenal cannulation of the pancreatic duct, in two different protocols. In the first protocol the administration of pentobarbital induces a mild anesthesia. Under this condition, amylase and chymotrypsin secretion remained parallel after cholecystokinin stimulation. In a second protocol, a deeper and constant anesthesia was attained with Fluothane resulting in a lower basal protein output than in the first protocol. Pancreatic secretion was collected under intravenous secretin perfusion (4.5 clinical units∙kg−1∙h−1). After stabilization and basal collection periods, pancreatic secretion was stimulated with an i.v. bolus injection of either cholecystokinin (2 Ivy dog units/kg), caerulein (0.1 μg/kg), or carbachol (6 μg/kg). Upon stimulation of the pancreas, protein output increased an average of 30-fold and there was a concomitant 20–25% decrease in the ratio of the specific activities of amylase to chymotrypsin which resulted from a greater increase in the specific activity of chymotrypsin in pancreatic juice after stimulation of secretion. Thus, under appropriate conditions, nonparallel secretion of enzymes by the exocrine pancreas can be demonstrated in yet another experimental model. Furthermore, the proportion of amylase and chymotrypsin activities in pancreatic juice are once more shown to be dependent, up to a threshold, upon the rate of protein output by this exocrine gland.
A comparison of the inhibitory effects of somatostatin-14, -25, and -28 on motility of the guinea pig ileum
Authors: McIntosh Christopher H. S. , Bakich Victoria , Kwok Yin Nam , Brown John C.
Published: April 2011

A number of studies have suggested that somatostatin-14 (SS-14) and somatostatin-28 (SS-28) exhibit a similar spectrum of biological activities but have different potencies. In the present study the effects of SS-14, SS-28, and somatostatin-25 on electrically induced contractions of the guinea pig ileum have been compared. All three peptides exhibited equipotent inhibitory effects. Inhibition was obtained at a threshold concentration less than 10−10 M, with maximal inhibition at 10−7 M and IC50 values of 6.0–6.5 × 10−10 M. The N-terminal 14 amino acid fragment of SS-28 had no effect either on motility, when added alone, or on the actions of SS-28, suggesting that this region of the molecule is not critical for biological activity.
Role of electrical activity and trophic factors during cholinergic development in dissociated cultures
Authors: Brenneman Douglas E.
Published: April 2011

The role of electrical activity in the developmental regulation of cholinergic neurons was investigated in dissociated spinal cord – dorsal root ganglion (SC-DRG) cultures. Application of tetrodotoxin (TTX) during the first 6 days after plating had no effect on choline acetyltransferase (CAT) activity. Suppression of electrical activity during the 7th day decreased CAT to 68% of control. These decreases in CAT activity were still apparent 2 weeks after removal of the TTX. GABAergic neurons, as indicated by glutamic acid decarboxylase activity and high affinity [3H]GABA uptake, were not affected by TTX treatment. Addition of 8-bromo-cAMP or conditioned medium obtained from SC-DRG cultures at certain developmental periods produced dose-dependent increases in CAT levels on TTX-treated cultures as compared with those treated with TTX alone. Similar studies with 8-bromo-cGMP revealed no significant effects on CAT activity. Vasoactive intestinal peptide (VIP) produced a dose-dependent increase in CAT activity when added to cultures between days 12 and 14. Similar studies conducted on younger cultures (days 5–7) or older cultures (days 21–23) revealed no increases in CAT activity. Addition of 0.1 nM VIP to TTX-treated cultures resulted in CAT levels which were not significantly different from those of electrically active controls. These data suggest that cyclic AMP, VIP, and trophic substances in conditioned medium may have roles in the mechanism of cholinergic toxicity produced by electrical blockade of developing spinal cord neurons.
Topographic studies of the effects of microinjections of muscimol on the hypothalamic control of feed intake in sheep
Authors: Girard C. L. , Seoane J. R. , Matte J. J.
Published: April 2011

Ten sheep were used to define the anatomical basis for the feeding systems sensitive to gamma-aminobutyric acid, by using intrahypothalamic microinjections of the gamma-aminobutyric acid agonist, muscimol. In satiated sheep, 1 μL of muscimol (0.5 nmol/μL) elicited feeding when injected into paraventricular, ventromedial, and anterior hypothalamic areas. Similar injections into 39 sites tested in 6-h fasted sheep failed to decrease feed intake. The data suggest that neurons sensitive to gamma-aminobutyric acid in medial hypothalamus may be involved in the initiation of feeding.
Mechanisms of α-adrenoceptor mediated contractions of rat mesenteric artery
Authors: Kannan M. S. , Seip A. E.
Published: April 2011

The nature of the calcium channels associated with the activation of alpha-adrenoceptors in vascular smooth muscle has been investigated. The inhibitory effects of nitrendipine, a calcium antagonist, were studied on the contractions elicited by α-adrenoceptor agonists in rat superior mesentric artery. Responses to equieffective concentrations of phenylephrine (α1-adrenoceptor agonist), clonidine and BHT-920, (α2-adrenoceptor agonists), and noradrenaline (nonselective agonist) were inhibited differentially by the calcium antagonist, with the sensitivity order being as follows: BHT-920 = clonidine > phenylephrine > noradrenaline. When the contractions to two doses of noradrenaline were compared, the low dose response was more sensitive to nitrendipine inhibition than the high dose response. This differential inhibition was not seen for noradrenaline in the presence of verapamil or for phenylephrine in the presence of nitrendipine. The contractions of the vessel to the agonists in zero calcium conditions were not significantly different from each other. The sensitivity differences among the agonists to nitrendipine may arise from differences in the postreceptor mechanisms of activation. The differential sensitivity of noradrenaline responses suggests a greater heterogeneity of calcium channels than those available for the other agonists.
Neurointermediate lobe transplanted under the kidney capsule modifies the activity of the neurointermediate lobe in situ, but does not respond to opiate treatment
Authors: Gianoulakis Christina , Gupta Alka
Published: April 2011

To investigate the possibility of a direct effect of morphine on the pars intermedia cells of the pituitary gland, rat neurointermediate lobes (NIL) were transplanted under the kidney capsule. At 2 and 8 days posttransplantation the NIL transplant had maintained its morphological integrity. However, at 15 days posttransplantation the morphological integrity of the NIL transplant had started to deteriorate. The NIL transplant contained, synthesized, and released β-endorphin-like peptides. It was noticed that there was very little β-endorphin in the radiolabelled biosynthesized products, suggesting that either the maturation processing of proopiomelanocortin was modified, or that β-endorphin was released immediately as soon as it was formed and did not accumulate in the tissue. In support of the latter possibility was the elevated content of β-endorphin-like immunoreactivity in the sera of rats with a NIL under the kidney capsule. Furthermore, the NIL transplant seemed to produce a substance or substances which could decrease the content, the biosynthesis and the release of β-endorphin-like peptides by the NIL in situ. Treatment with either morphine or naloxone for 5 days did not change the β-endorphin-like immunoreactivity content in the NIL transplanted under the kidney capsule. However, a distinct decrease in the β-endorphin-like immunoreactivity in the NIL in situ of animals with or without a NIL transplant was observed following the morphine treatment. Naloxone treatment induced a decrease in the β-endorphin-like immunoreactivity content in the hypothalamus, but had no effect on the β-endorphin-like immunoreactivity content in the anterior lobe and NIL of the pituitary gland in situ or in the NIL transplant.
Immunocytochemical demonstration of ornithine decarboxylase in the rat exocrine pancreas using the protein A–gold technique
Authors: Morisset Jean , Sarfati Patrice , Grondin Gilles
Published: April 2011

Previous studies from our laboratory have shown that caerulein, a cholecystokinin analog, can induce pancreatic growth. Because ornithine decarboxylase (ODC) could be involved in this process, it is of interest to localize and estimate ODC immunoreactivity in rat pancreatic acinar cells from control and caerulein-treated animals. This was carried out with the protein A–gold immunocytochemical technique. Rats received either saline (control) or caerulein at a dose of 1 μg∙kg−1 and were sacrificed 8 h after the first injection (control and caerulein group), 4 h after the second caerulein injection (second caerulein group), and 8 h after the third caerulein injection (third caerulein group). ODC immunoreactivity was revealed using a specific antibody. ODC was localized specifically in nuclei and rough endoplasmic reticulum (RER) of the pancreatic acinar cells and the number of gold particles was increased in both of these organelles by caerulein. Peak ODC immunoreactivity was observed in nuclei 4 h after the second caerulein injection, whereas it occurred 8 h after the third peptide injection in the RER. These studies are the first to demonstrate ODC localization in pancreatic acinar cells and show that the enzyme can be induced early upon growth stimulation of the organ by a cholecystokinin analog.
Adenosine modulation of hepatic arterial but not portal venous constriction induced by sympathetic nerves, norepinephrine, angiotensin, and vasopressin in the cat
Authors: Lautt W. Wayne , Legare Dallas J.
Published: April 2011

Intrinsic regulation of hepatic arterial blood flow depends upon local concentrations of adenosine. The present data show that i.a. infusions of adenosine cause dilation of the hepatic artery and inhibition of arterial vasoconstriction induced by norepinephrine, vasopressin, angiotensin, and hepatic nerve stimulation. Vasoconstriction induced by submaximal nerve stimulation (2 Hz) and norepinephrine infusions (0.25 and 0.5 μg∙kg−1∙min−1, i.p.v.) were equally inhibited by adenosine. Supramaximal nerve stimulation (8 Hz) was inhibited to a lesser extent. The data are consistent with the hypotheses that (a) adenosine causes nonselective inhibition of vasoconstrictor influences on the hepatic artery; and (b) adenosine antagonizes neurally induced vasoconstriction by a purely postsynaptic effect and does not decrease norepinephrine release. In contrast with the hepatic artery, the intrahepatic portal resistance vessels are not affected by even large doses of adenosine; neither responses in basal tone nor antagonism of vasoconstrictor effects of nerve stimulation, norepinephrine, or angiotensin could be demonstrated. The data are consistent with the hypothesis that the smooth muscle of the portal resistance vessels does not contain adenosine receptors, whereas adenosine receptors on the smooth muscle of the hepatic arterial resistance vessels are of major regulatory importance. Whether endogenous levels of adenosine can reach sufficient concentration to modulate endogenous constrictors remains to be determined.
Effects of 17β-estradiol on myometrial gap junctions and pregnancy in the rat
Authors: Mackenzie L. W. , Garfield R. E.
Published: April 2011

The effects of estradiol treatment on the development of myometrial gap junctions and premature labour were investigated using timed pregnant rats. In control animals myometrial gap junctions were infrequent between days 17 and 20 of pregnancy, but began to develop on day 21 and were at maximum frequency, size, and membrane area on day 22 during delivery. Gap junctions were completely absent from the myometrium 48 h after delivery. Animals treated with 500 μg 17β-estradiol/day starting on day 16 of pregnancy developed numerous myometrial gap junctions and delivered their pups prematurely on day 19. Similarly, treatment with 50 μg estradiol/day resulted in the development of myometrial gap junctions on day 20 of pregnancy and premature labour. However, treatment with various doses of estradiol up to and including 500 μg/day for 3 days beginning 1 day before delivery was not able to maintain the presence of myometrial gap junctions during the postpartum period. These results support the hypothesis that estradiol stimulates the development of myometrial gap junctions and that the presence of gap junctions in the myometrium is a requirement for the occurrence of term, as well as preterm labour. Furthermore, it is evident from this study that the postpartum regression of myometrial gap junctions is not dependent on the decrease in estradiol.
The effect of lidocaine compared with verapamil on the enhanced ventricular rhythm in the infarcted canine heart
Authors: Kinnaird Anne A. A. , Man Ricky Y. K.
Published: April 2011

Myocardial ischemia was produced in dogs by the occlusion of the left anterior descending (LAD) coronary artery for 24 or 48 h. After complete atrioventricular block was produced, enhanced ventricular rhythm was observed in all animals. The enhanced ventricular rhythm showed multiple QRS configurations and had spontaneous cycle lengths (SCL) of 397 ± 18 ms (n = 20) after 24 h of LAD occlusion and 446 ± 23 ms (n = 20) after 48 h of LAD occlusion. Overdrive pacing did not result in the termination of the enhanced ventricular rhythm in any experiment. Propranolol, as a cumulative dose of 1.5–2.0 mg/kg i.v., also did not abolish the enhanced ventricular rhythm. In 24-h infarcted hearts, lidocaine abolished the enhanced ventricular rhythm in 1 of 11 experiments. In the remaining 10 experiments, the ventricular SCL was increased from 401 ± 22 to 491 ± 26 ms after a cumulative dose of 8.8 ± 0.7 mg/kg of lidocaine. In the presence of verapamil, given as a cumulative dose of 0.60 ± 0.11 mg/kg, the ventricular SCL was increased from 401 ± 33 to 482 ± 64 ms (n = 9). In 48-h infarcted hearts, lidocaine abolished the enhanced ventricular rhythm in 5 of 11 experiments. Both lidocaine and verapamil increased the SCL of hearts in which the enhanced ventricular rhythm persisted. Analysis of variance showed that only the increase in SCL by lidocaine in 48-h infarcted hearts was statistically significant. The atrial and idioventricular rhythms in noninfarcted hearts responded differently to lidocaine and verapamil. The results suggest that some electrophysiological effects of antiarrhythmic drugs in the normal heart may not be applicable to those in the diseased situation.
Comparison of the effects of 3-ethoxycarbonyl-1,4-dihydro-2,4-dimethylpyridine and 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine on ferrochelatase activity and heme biosynthesis in chick embryo liver cells in culture
Authors: Marks G. S. , Allen D. T. , Sutherland E. P. , McCluskey S. A. , Whitney R. A.
Published: April 2011

3-Ethoxycarbonyl-1,4-dihydro-2,4-dimethylpyridine (EDP) was shown to lack the ferrochelatase-lowering activity of 3,5-diemoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) in chick embryo liver cells in culture. This was attributed to the inability of EDP to cause destruction of the heme moiety of cytochrome P-450 with concomitant formation of N-methylprotoporphyrin IX. EDP was less potent as a porphyrinogenic agent than DDC and caused the accumulation of uroporphyrin, heptacarboxylic porphyrin, and coproporphyrin in contrast with DDC which caused primarily protoporphyrin to accumulate. The inactivity of EDP as a ferrochelatase-lowering agent and its low porphyrinogenic potency was explained, at least in part, by its rapid transformation in aqueous solution to other nondihydropyridine products. The two ethoxycarbonyl substituents of DDC are therefore essential for N-methylprotoporphyrin formation, ferrochelatase-lowering activity, and optimal porphyrin-inducing activity.
Prostaglandin E2 binding sites in porcine oxyntic mucosa: effects of salicylates
Authors: Tepperman B. L. , Soper B. D.
Published: April 2011

These studies were designed to examine the changes in the characteristics of prostaglandin E2 (PGE2) binding to porcine oxyntic mucosa in the response to oral ingestion of salicylates. Either acetylsalicylic acid (ASA) or salicylic acid (SA) was administered to conscious pigs (100 mg/kg in 30 mL of an equimolar concentration of NaHCO3) once a day for 1, 3, 10, or 20 days. In control experiments a similar volume of 0.3 M NaHCO3 was administered for similar durations. Mucosal ulceration and the characteristics of the binding of [3H]PGE2 to a 30 000 × g membrane preparation of oxyntic mucosa were examined. Generation of mucosal PGE2 was measured by radioimmunoassay. ASA treatment resulted in an increase in the number and severity of mucosal ulcers and a decrease in PGE2 levels within the first treatment day. By day 20 the degree of ulceration had decreased in spite of a persistent reduction of mucosal PGE2 generation. A variable degree of ulceration was observed in SA-treated animals. In control animals only a single class of binding sites for [3H]PGE2 was evident. After 3 days of ASA treatment a second class of binding sites with a high affinity dissociation constant appeared. There was a decrease in the high affinity binding of [3H]PGE2 after 20 days of ASA ingestion. Low affinity binding was not altered. ASA treatment resulted in a significant increase in specific binding capacities for both families of binding sites. SA treatment did not consistently alter PGE2 binding characteristics from control at any time period studied. These data suggest that SA treatment results in a small degree of mucosal damage in the absence of a significant reduction in tissue generation of PGE2 or changes in PGE2 binding. Damage in response to ASA ingestion was associated with a reduction in both endogenous synthesis of PGE2 and an increase in the concentration of both low and high affinity binding sites for PGE2. The reduction in mucosal ulceration on day 20 in spite of depressed endogenous PGE2 coincides with an increase in PGE2 binding.
Insulin-like growth factor inhibition of growth hormone secretion
Authors: Sheppard M. S. , Bala R. M.
Published: April 2011

Somatomedins – insulin-like growth factors (SM/IGF) are growth hormone (GH) dependent serum growth factors. There is some evidence that IGF inhibit GH release (negative feedback) in 3- to 24-h incubations of cultured rat adenohypophysial cells. We have used acutely dispersed noncultured rat adenohypophysial cells to study the dynamics of IGF on GH secretion. In this system both IGF-I and IGF-II (100 ng/mL) slightly, but significantly, decrease the cumulative GH released by human pancreas growth hormone releasing factor 1–40 (GRF) and the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine. The inhibition is small (16%) and usually not statistically significant until 2 h of incubation. The inhibition with IGF is additive to that produced with low concentrations of somatostatin. The IGF also sigificantly decrease the rate of GH release in all time periods tested (0–1, 1–2, 2–3 h). In addition, the IGF decrease the quantity of [14C]leucine protein eluted at the position of labelled rat GH on Sephadex G75, which would include newly synthesized GH extracted from the cells. Thus we conclude that the decreased GH released may be due to an effect of IGF on both rate of release and on GH synthesis.
Effects of nifedipine on hepatic blood volume in cats: indirect venoconstriction and absence of inhibition of postsynaptic α2-adrenoceptor responses
Authors: Segstro R. , Seaman K. L. , Innes I. R. , Greenway C. V.
Published: April 2011

Intravenous administration of hypotensive doses (30–200 μg/kg) of nifedipine to cats anesthetized with pentobarbital caused an increase in cardiac output accompanied by hepatic venoconstriction. The hepatic venoconstriction and the increase in cardiac output were abolished in animals in which the hepatic sympathetic nerves were cut, the adrenal glands were excluded, and the kidneys were removed. This contrasts with the indirect hepatic venoconstrictor action of isoproterenol which was shown previously not to be abolished by these procedures. Further experiments showed that the hepatic venoconstrictor effect of nifedipine was blocked by removal of the kidneys, but not by removal of the hepatic sympathetic nerves and adrenals. These results support the hypothesis that venoconstriction plays an important role when drugs produce increased cardiac output. In nephrectomized animals, nifedipine had no direct effects on hepatic blood volume and it did not alter the effects of infusions of norepinephrine on hepatic blood volume, which have previously been shown to be mediated through α2-adrenoceptors. However, it did reduce the hepatic venous responses to hepatic sympathetic nerve stimulation by 30%.
Effects of bromocryptine on hepatic blood volume responses to hepatic nerve stimulation in cats
Authors: Greenway C. V. , Burczynski F. , Innes I. R.
Published: April 2011

Arterial pressures, portal pressures, and hepatic blood volumes were recorded after hepatic denervation in cats anesthetized with pentobarbital. Bromocryptine (50 μg/kg) lowered arterial pressure but did not significantly change portal pressure or hepatic blood volume. However, both portal pressure and hepatic blood volume responses to hepatic nerve stimulation were significantly depressed after bromocryptine especially at low frequencies of stimulation. Responses to intraportal infusions of norepinephrine were significantly impaired only at the highest dose. The inhibitory effect of bromocryptine on the neural responses may, therefore, involve a presynaptic inhibition of norepinephrine release, but the mechanism requires further study. These data provide further suport for the hypothesis that drugs which impair hepatic venous responses to sympathetic stimuli cause significant impairment of postural reflexes and orthostatic hypotension during clinical use.
An upper limit for the electrogenic Na–K pump contribution to maximum diastolic potential in feline cardiac Purkinje fibers in steady state
Authors: Hill Jr. Joseph A. , Trantham Joey L. , Browning David J. , Grant Augustus O. , Strauss Harold C.
Published: April 2011

We have estimated an upper limit for the electrogenic contribution of the Na–K pump to diastolic transmembrane potential. We simultaneously monitored the maximum diastolic potential and the extracellular space potassium activity during exposure to a very high concentration of ouabain. Exposure to ouabain caused a depolarization of approximately 3 mV (n = 33 experiments) over 34 ± 3 s (mean ± standard error) prior to any change in extracellular K activity. In four experiments, we monitored intracellular sodium activity and observed it to rise with approximately the same temporal lag (delay = 26 ± 7 s). We also measured relative membrane conductance in one series of experiments and observed it to decrease to 91 ± 2% of its control value by the time extracellular space K began to rise. Following the initial increase in extracellular space K activity the subsequent membrane depolarization is shown to be accurately predicted solely from the measured increase in extracellular space K activity as calculated from the Goldman equation. Limitations of the method and possible interpretations of the data are discussed. We interpret this ouabain-induced depolarization that occurs prior to the rise in external K to be an upper limit to the Na–K pump's electrogenic contribution to steady-state membrane potential.
Differential effects of adenosine and verapamil on histamine vascular contractions
Authors: Tozzi Carol A. , Merrill Gary F.
Published: April 2011

The present study was undertaken to compare the effects of adenosine and verapamil on histamine-induced contractions in rabbit vascular smooth muscle. Ring segments of rabbit femoral artery were isometrically mounted and contractile responses to histamine (10−7 to 10−4 M) were recorded. Verapamil (10−5 to 10−4 M) and adenosine (10−5 to 10−4 M) produced significant (P < 0.05) shifts to the right of the histamine dose–response curve in normal physiological salt solution (PSS). Adenosine (10−4 M) had no effect on the contractile responses to histamine in calcium-deplete PSS but significantly (P < 0.01) increased the rate of relaxation (−dT/dt, 16.1 ± 2.3 mg/s before adenosine, 53.7 ± 7.0 mg/s during adenosine). In calcium-free PSS, verapamil (10−4 M) had no effects on histamine-induced contractions, nor did it affect the spontaneous rate of relaxation. These findings suggest that the relaxant responses to adenosine, like verapamil, are partially mediated through blockade of external calcium influx, while adenosine, unlike verapamil, appears to have an additional intracellular mode of action.
Uptake of the hormone 1,25-dihydroxyvitamin D3 by the dog liver
Authors: Gascon-Barré Marielle , Vallières Sylvie , Huet Pierre-Michel
Published: April 2011

The hepatic uptake of the hormone 1,25-dihydroxyvitamin D3 has been studied, in vivo, using the multiple indicator dilution technique. The fractional uptake of 1,25-dihydroxyvitamin D3 during a single circulatory passage across the dog liver has been estimated at 34.4 ± 3.3% while its hepatic clearance was estimated at 364.3 ± 94.1 mL/min. The hepatic uptake of 1,25-dihydroxyvitamin D3 is discussed in relation to its systemic bioavailability following intravenous or oral administration as well as in relation to the hepatic uptake of other vitamin D sterols; it is postulated that the hepatic uptake of vitamin D sterols does not seem to be mediated by specific receptors on the liver plasma membrane; it seems, however, that the hepatic uptake of vitamin D sterols may be inversely related to their relative affinity for the circulating carrier, the vitamin D binding protein.
Session on sodium and calcium in the management of hypertension summary of remarks of discussant and chairman
Authors: Rabkin (Discussant) Simon W. , Klassen (Chairman) Gerry A.
Published: April 2011

Despite the attractiveness of proposals for dietary therapy of mild hypertension it has not been possible to reach agreement for such a recommendation (Consensus Development Conference on the Management of Mild Hypertension in Canada, 1984). We will discuss the evidence concerning a therapeutic role for moderate sodium restriction or calcium supplementation in the control of mild hypertension. It has been accepted that dietary therapy, if efficacious, would be preferable to a pharmacologic approach. However, there is a paucity of evidence that modification of these two factors will effectively control hypertension or prevent its complications.
The role of sodium restriction in the management of hypertension
Authors: Morgan Trefor , Nowson Carol
Published: April 2011

More than 50 studies have investigated the effect of altered sodium intake on blood pressure. A regression line drawn through the change in blood pressure and change in sodium intake indicates that blood pressure alters about 10 mmHg (1 mmHg = 133.322 Pa) for every 100 mmol/day alteration in sodium intake, a change similar to that observed in between-population "studies." The studies that have failed to show a change in blood pressure have usually been in people with a blood pressure less than 130/90 mmHg. Normotensive people appear to tolerate a higher intake of sodium before blood pressure rises, but if increased sufficiently, blood pressure rises in most people. Sodium restriction reduces blood pressure in people with severe hypertension, moderate hypertension and mild hypertension. It may be the cause of blood pressure increase associated with age and the reason for the higher prevalence of hypertension and vascular disease in Western communities. Sodium restriction should be used to treat people with elevated blood pressure.
Alterations of dietary calcium intake as a therapeutic modality in essential hypertension
Authors: Resnick Lawrence M.
Published: April 2011

Alterations of calcium metabolism in hypertensive disease have been increasingly observed, although the specific manner in which these alterations contribute to the increased blood pressure remains unclear. We have studied calcium metabolism in essential hypertension and have adopted an approach based on analysis of renin system activity, which emphasizes the heterogeneity of human hypertensive disease. With this approach we have defined parallel deviations of plasma renin activity, circulating ionized calcium, and calcium-regulating hormones, which suggest a calcium deficiency in some hypertensives and, an excess of calcium in others. These deviations can be used to predict and may mediate the blood pressure sensitivity of hypertensives to dietary salt, and may also target those individuals most likely to benefit from oral calcium supplementation. Calcium itself has enhanced antihypertensive effects in low renin subjects, having lower ionized calcium and higher endogenous 1,25-dihydroxyvitamin D values, and in subjects on higher dietary salt intakes. Calcium may alter pressure, at least in part, by suppressing endogenous vitamin D metabolites and by stimulating calcitonin secretion. We hypothesize that calcium-regulating hormones participate in the physiology of the renin–angiotensin system and in the pathophysiology of human hypertension.
Obesity: overview of pathogenesis and treatment
Authors: Leiter Lawrence A.
Published: April 2011

This paper presents an overview of selected current concepts of the pathogenesis and treatment of obesity. It has been estimated using the 1981 Canada Fitness Survey data that 14.1% of Canadian adult men and 20.6% of women are greater than 20% above reference table weight. Recent advances in adipocyte metabolism and control have shown that hyperplastic obesity can occur at any age and that there are differences in the replicative rate of adipocyte precursor cells from the massively obese. Furthermore, a number of the complications of obesity, including hypertension, have been related to regional body fat distribution, independent of total body fat. It is suggested that some of the controversy on the relationship between body weight/weight loss and hypertension may be due to failure to account for this. There is now suggestive evidence that abnormalities in diet-induced thermogenesis and (or) brown adipose tissue may result in human obesity. The roles of the major treatment modalities (diet, behaviour therapy, and exercise) are reviewed as are the potential hazards of the weight loss process.