bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional contractile responses in pulmonary artery to α- and β-adrenoceptor agonists
Authors: Kolbeck Ralph C. , Speir Jr. William A.
Published: April 2011

Contractile sensitivity and reactivity to α- and β-adrenoceptor stimulation was studied in incubated rabbit pulmonary artery cylindrical segments of differing diameters. Distinct differences were noted between the responses of extra- and intra-pulmonary pulmonary arteries to norepinephrine and isoproterenol. The sensitivity to norepinephrine was largest in the intrapulmonary pulmonary arteries. Arterial reactivity to norepinephrine was greatest in the larger of the intrapulmonary vessel segments, diminishing considerably as the vessels became smaller. Cocaine did not cause substantial alterations in the response of any of the arterial segments to the α-agonist. Phentolamine, however, exerted its influence primarily in the smaller arterial segments. Vascular sensitivity to isoproterenol was least in the intrapulmonary pulmonary arteries. These smaller vessel segments, however, were more reactive to isoproterenol than were the extrapulmonary pulmonary arterial segments. Propranolol, at a concentration of 10−8 M, was an effective antagonist of the β-agonist; at a concentration of 10−7 M, however, this antagonist was related to isoproterenol-induced arterial contraction, apparently by stimulation of α-receptor sites. The results of this study demonstrated a regional heterogeneity in the contractile response of the pulmonary artery to α- and β-stimulation. The extrapulmonary arterial segments were found to be more sensitive to β-stimulation than were the smaller, intrapulmonary, segments. The intrapulmonary arterial segments, on the other hand, were found to be more sensitive to α-stimulation than were the extrapulmonary segments.
Detection of ethanol in urine of abstaining alcoholics
Authors: Tang B. K.
Published: April 2011

A simple method using gas chromatography – mass spectrometry was developed to determine a low concentration of ethanol in urine. The detection limit was 0.02 mM ethanol. A mean ± SD ethanol concentration in urine of 0.21 ± 0.17 mM was measured in 11 alcoholics after 14 days abstention, a level at least 10 times higher than that of control subjects who had no alcoholic drinks during a period of 7 days prior to the test.
The metabolic cost of fever
Authors: Baracos Vickie E. , Whitmore W. T. , Gale R.
Published: April 2011

Indirect calorimetry has been employed to demonstrate that fever and infection result in increased metabolic heat production. This response contributes, with reduced dietary energy intake, to negative energy balance in the infected host and constitutes a metabolic "cost". Clinical and experimental studies concerning quantitative aspects of metabolic heat production during fever are summarized. The possible adaptive value of increased heat production in the context of host defence reactions is discussed. The magnitude of increased heat production varies with the severity and duration of the insult, the nutritional and metabolic status of the host, treatment with various drugs, and the ambient temperature at which the measurements are made. More information about these factors is required to assess the metabolic and nutritional needs of individual patients during a febrile illness and subsequent recovery.
Thermoregulatory physiology of menopausal hot flashes: a review
Authors: Kronenberg Fredi , Downey John A.
Published: April 2011

Hot flashes during the climacteric years have long been a frequent clinical complaint, generally considered within the realm of the internist, gynecologist, or endocrinologist. Yet the underlying mechanism of hot flashes remains unknown. Only within the past 10 years has there been significant research on hot flashes as a disturbance of thermoregulation. This paper focuses on thermoregulatory aspects of hot flashes, reviewing current knowledge of the thermoregulatory physiology and endocrinology of hot flashes and discussing future avenues for research. Hot flashes are compared with fever in terms of thermoregulatory changes and speculated mechanisms. Although several substances in the peripheral circulation are found in increased concentrations during hot flashes, none is a trigger for a hot flash. The pattern of hot flash occurrence is striking in its regularity, and the possibility of endogenous rhythmicity is discussed. Recently, investigators have begun to explore a primate model of menopausal hot flashes. These studies are summarized. Finally, the multiple effects of estrogen on various systems of the body and their interrelationships are discussed. An understanding of the mechanism of hot flashes would not only be of importance to women suffering with hot flashes but would further our knowledge of thermoregulatory function and the interactions between thermoregulatory and reproductive systems.
Diabetes mellitus and thermoregulation
Authors: Scott A. R. , Bennett T. , Macdonald I. A.
Published: April 2011

Diabetes mellitus is accompanied by a variety of alterations in metabolic, cardiovascular, and neuronal function. This paper provides a comprehensive review of the ways in which these pathophysiological aspects of diabetes may impair thermoregulatory function. The influence of diabetic neuropathy and vasculopathy on the control of peripheral blood flow is reviewed and the additional effects of changing levels of blood glucose and insulin are discussed. Both hypoglycaemia and diabetic ketoacidosis are associated with hypothermia, but the reasons for this in ketoacidosis are not clear. Impairment of heat conservation may contribute to and could be a consequence of autonomic neuropathy. The final section of the paper describes a study of our own in which metabolic stability was maintained by infusing insulin intravenously before and during the determination of the thermoregulatory responses to acute cold stress. Under these conditions, there was impairment of reflex vasoconstriction in the limbs of diabetics with neuropathy. This failure to reduce heat loss resulted in half the diabetics with neuropathy shivering in response to moderate cooling, which in some subjects was accompanied by a fall in core temperature. Diabetics without neuropathy and nondiabetics neither shivered nor dropped core temperature.
The roles of monoaminergic neurotransmitters in thermoregulation
Authors: Zeisberger E.
Published: April 2011

Recent studies of the organization of the thermoregulatory system and evaluation of experimental evidence from electrophysiological, neuropharmacological, and neuroanatomical studies suggest that the monoamines noradrenaline and 5-hydroxytryptamine are involved in modulations of thermoregulation rather than in thermoregulation per se: they do not seem to transfer specific thermal information but rather modulate the signals passing from thermosensors to thermoregulatory effectors. Theoretically, the central monoamines could be modulating the input from thermosensors, or the central integration of thermal signals, or the outflow of signals to thermoregulatory effectors. The modulatory action of the monoamines on thermosensitive and thermointegrative hypothalamic neurons is best documented. There, the monoamines 5-hydroxytryptamine and noradrenaline seem to act as antagonists, which enhance or diminish the effects of thermal afferents mediated by other transmitters. Moreover, the antagonistic monoaminergic systems are apparently interconnected and can influence each other at a lower brain stem level. The activity in central monoaminergic systems can also be modified by neurohumoral feedback mechanisms from the periphery. By means of these interrelations the vegetative responses of the organism can be corrected and optimized.
Hypertension: Blood pressure regulating systems: cellular, integrative, and therapeutic aspects
Authors: Korner Paul I. , Leenen Frans H. H.
Published: April 2011

This is only the second time in the long history of the International Physiological Congresses that a symposium on hypertension has formed part of the official satellite programme. After the 1983 IUPS Congress in Sydney, John Chalmers organized a magnificent satellite meeting at the Flinders Medical Centre in South Australia and we felt that we wished to continue the "tradition." Hypertension research has provided a wonderful example in recent years of how exciting it can be to apply very basic discoveries to the solution of practical problems. This meeting breaks new ground in being the first scientific event sponsored jointly by the Canadian Hypertension Society and the Australian High Blood Pressure Council. The meeting was made possible by generous financial support from Pfizer Canada and Pfizer Australia with, as co-contributors, Bayer Germany and Sandoz Australia. We would also like to acknowledge the help of Mrs. A. Garat of Pfizer Canada Medical Services in the organization of the meeting and Dr. Andrew Rankin who was responsible for all local arrangements.The Hypertension Satellite was held at Whistler, B.C., July 19–21, 1986, following the 30th International Congress of the International Union of Physiological Sciences in Vancouver. It provided a good forum for interdisciplinary information exchange. It also proved to be a pleasant social occasion in the beautiful setting of the coastal range of the Canadian Rockies. There were 48 invited speakers from Canada, Australia, Europe, the U.S.A., Japan, and New Zealand. We were fortunate in having as our patrons two great names in hypertension research, Dr. Arthur Guyton and Dr. Sydney Friedman.Emphasis was on a large range of mechanisms that regulate blood pressure. There were sessions on cell biology, the kidney, autonomic nervous regulation, peptides (including, of course, atrial natriuretic peptide and arginine vasopressin), and pathogenesis. The proceedings provide an up-to-date account of the position of the current "state of the art" in a number of important areas.
Renal nerves and experimental hypertension: evidence and controversy
Authors: Kline Robert L.
Published: April 2011

Noradrenergic fibers innervate various parts of the nephron and can contribute to sodium and water homeostasis by influencing hemodynamic variables, tubular reabsorptive mechanisms, and renin release. As renal function is considered to be a primary determinant of arterial pressure, efferent renal nerves may be an important link between the central nervous system and the kidney in the development and maintenance of hypertension. Little is known about the relative importance of renal nerves and their interactions with other factors in influencing renal function chronically. There is disagreement about the evidence for enhanced noradrenergic drive to the kidney in hypertensive rats, as the renal nerve firing rate, neurotransmitter release and metabolism, and receptor properties are generally not studied in association with measurements of renal function. However, chronic renal denervation has been shown to significantly affect arterial pressure in diverse forms of experimental hypertension in rats, including genetic models, as well as renovascular, mineralocorticoid, neurogenic, and angiotensin II hypertension. The actual mechanisms responsible for this effect of renal denervation are not clear, but presumably reflect changes in the arterial pressure – urinary sodium output relationship. On the whole, there is reasonable correlation between neurophysiological, biochemical, and renal denervation studies in the spontaneously hypertensive rat, suggesting that renal nerves do play a role in the onset of hypertension in these animals. The effect of renal denervation in other models of hypertension seems less clear, with recent reports showing that renal denervation does not alter the hypertensive process in renovascular, mineralocorticoid, and salt-related hypertension. These contradictory findings are not easily explained, but there is some indication that elevated sodium intake may alter the response to renal denervation. Resolution of these controversies must await a better understanding of the influence of renal nerves on renal function and arterial pressure in normal and hypertensive animals.
Forebrain mechanisms in neurogenic hypertension
Authors: Ciriello John
Published: April 2011

In recent years a considerable amount of experimental evidence has suggested that forebrain structures are involved in the pathogenesis of high arterial pressure (AP). However, little is known about the location and function of these supramedullary structures in the hypertensive process. This report reviews a series of studies done to identify the location and to determine the contribution of some forebrain structures to both the development and maintenance of the elevated AP following selective aortic baroreceptor deafferentation (ABD). In the first series of studies, it was demonstrated that the elevated AP resulting from ABD was associated with increased metabolic activity in several forebrain structures: the paraventricular nucleus of the hypothalamus (PVH), supraoptic nucleus, nucleus circularis, median preoptic nucleus, subfornical organ (SFO), and central nucleus of the amygdala. In the second series, bilateral electrolytic lesions of the PVH were shown to prevent the development of and (or) reverse the elevated AP after ABD. Similarly, bilateral microinjections of the neurotoxin kainic acid into the PVH were shown to reverse the increased AP after ABD. In the final series, electrolytic lesions of the SFO were shown to attenuate the rise in AP after ABD and (or) to reduce the elevated AP to a level that remained above control values. Taken together, these data suggest that the PVH and SFO are components of a neuronal circuit involved in the hypertensive process following ABD, and that the SFO likely exerts its effect through the PVH.
Calcium handling in vasoconstriction to stimulation of alpha1- and alpha2-adrenoceptors
Authors: Timmermans Pieter B. M. W. M. , Chiu Anddrew T. , Thoolen Martin J. M. C.
Published: April 2011

Vasoconstriction to stimulation of postsynaptic alpha1- and alpha2-adrenoceptors involves different mechanisms of Ca2+ mobilization. Alpha2-adrenoceptor-mediated vasoconstriction in vivo as well as in vitro is invariably and effectively antagonized by Ca2+ channel blockers, such as nifedipine or verapamil, and is therefore primarily carried by influx of extracellular Ca2+. On the other hand, alpha1-adrenoceptor stimulation has been linked to both influx of extracellular Ca2+ and release of Ca2+ from intracellular stores. The sensitivity of alpha1-adrenoceptor-mediated vasoconstriction to blockade by Ca2+ channel antagonists depends on how much both mechanisms of Ca2+ mobilization contribute to the contraction process, and varies between vascular tissues and alpha1 -adrenoceptor agonists. The experimental evidence for the differential utilization of Ca2+ in vasoconstriction to alpha1- and alpha2-adrenoceptor stimulation is reviewed.
Atrial natriuretic peptides in man
Authors: Nicholls M. Gary , Ikram Hamid , Crozier Ian G. , Espiner Eric A. , Yandle Tim G.
Published: April 2011

Research on the physiological role of atrial peptides in man is limited, and the potential for these peptides, or more stable analogues, in therapeutics is uncertain. It is clear, however, that plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP) are increased in volunteers taking a high sodium diet, and are elevated in patients with heart failure, chronic renal failure, and primary aldosteronism. There is suggestive evidence that IR-ANP levels are increased also in essential hypertension, although overlap with normotensives is considerable. Injection or infusion of artrial peptides into man results in a diuresis, an increased output of urine electrolytes, a fall in blood pressure and a rise in heart rate, suppression of aldosterone and sometimes of renin also, and stimulation of norepinephrine. In essential hypertensives, urinary effects may be greater than in normotensives. Heart failure patients show a rise in cardiac output and falls in both systemic and pulmonary arterial pressure. Over the next few years and especially if specific antagonists can be developed, the physiologic and pathophysiologic roles of atrial peptides in normal man and in clinical disorders should be clarified. It is possible that stable analogues of atrial peptides will find a place in the treatment of cardiac failure, renal failure, and perhaps hypertension.
Secretory form of atrial natriuretic polypeptide as cardiac hormone in humans and rats
Authors: Nakao Kazuwa , Sugawara Akira , Shiono Shozo , Saito Yoshihiko , Morii Narito , Yamada Takayuki , Itoh Hiroshi , Mukoyama Masashi , Arai Hiroshi , Sakamoto Makoto , Imura Hiroo
Published: April 2011

To elucidate the secretory form of atrial natriuretic polypeptide from the atrium, the molecular form of atrial natriuretic polypeptide in the perfusate from the isolated beating rat heart and in plasma taken at the coronary sinus of 10 patients during cardiac catheterization has been investigated using high performance gel permeation chromatography and reverse phase high performance liquid chromatography coupled with radioimmunoassay for atrial natriuretic polypeptide. Atrial natriuretic polypeptide in the perfusate from the rat heart showed a single peak eluting at the position of a low molecular weight form of atrial natriuretic polypeptide, without any detectable amounts of atrial natriuretic polypeptide with high molecular weights. The major component of atrial natriuretic polypeptide in the rat heart perfusate co-migrated with rat α-atrial natriuretic polypeptide in reverse phase high performance liquid chromatography. In 9 out of 10 patients atrial natriuretic polypeptide in plasma taken at the coronary sinus revealed a single peak of atrial natriuretic polypeptide emerging at the position of human α-atrial natriuretic polypeptide in gel filtration. Only one plasma sample had a small quantity of high molecular weight forms with the predominant low molecular weight form of atrial natriuretic polypeptide. The major component of atrial natriuretic polypeptide in the plasma extract from the coronary sinus was identified with human α-atrial natriuretic polypeptide. These results indicate that α-ANP, a 28-amino acid polypeptide, is secreted as a cardiac hormone into the coronary blood stream from the atrium.
The effects of pH on force and stiffness development in mouse muscles
Authors: Renaud J. M. , Stein R. B. , Gordon T.
Published: April 2011

Changes in force and stiffness during contractions of mouse extensor digitorum longus and soleus muscles were measured over a range of extracellular pH from 6.4 to 7.4. Muscle stiffness was measured using small amplitude (<0.1% of muscle length), high frequency (1.5 kHz) oscillations in length. Twitch force was not significantly affected by changes in pH, but the peak force during repetitive stimulation (2, 3, and 20 pulses) was decreased significantly as the pH was reduced. Changes in muscle stiffness with pH were in the same direction, but smaller in extent. If the number of attached cross-bridges in the muscle can be determined from the measurement of small amplitude, high frequency muscle stiffness, then these findings suggest that (a) the number of cross-bridges between thick and thin filaments declines in low pH and (b) the average force per cross-bridge also declines in low pH. The decline in force per cross-bridge could arise from a reduction in the ability of cross-bridges to generate force during their state of active force production and (or) in an increased percentage of bonds in a low force, "rigor" state.
Evidence for liver as the major site of the diet-induced thermogenesis of rats fed a "cafeteria" diet
Authors: Ma Stephanie W. Y. , Nadeau Brita E. , Foster David O.
Published: April 2011

The resting metabolic rates [Formula: see text] of rats fed chow (CH) or a "cafeteria" (CAF) diet of highly palatable human foods were measured at thermoneutrality (28 °C) before and shortly after two-thirds hepatectomy or sham operation, and again after administration of propranolol (5 mg/kg). CAF rats initially had a 17% and 1.2 mL/min higher mean resting [Formula: see text] than CH rats, a difference usually considered to represent the diet-induced thermogenesis (DIT) that CAF rats develop during overconsumption of the diet. Sham operation did not significantly affect resting [Formula: see text] in either diet group. Two-thirds hepatectomy decreased [Formula: see text] by about 1.0 mL/min more (125% more) in CAF rats than in CH rats, from which it may be estimated that the CAF rats initially had a liver [Formula: see text] about 1.6 mL/min higher than that of the CH rats, a difference more than sufficient to fully account for their apparent DIT. Propranolol did not significantly affect the [Formula: see text] of CH rats. It reduced the [Formula: see text] of sham-operated CAF rats by 0.94 ± 0.08 mL/min (12%), but had a significantly smaller effect [Formula: see text] in partially hepatectomized CAF rats. This difference suggests that about 70% of the propranolol-inhibitable fraction of the elevated [Formula: see text] of the CAF rats, presumably a measure of sympathetically mediated DIT, resided in the liver. This study thus points to the liver as the major (70–100%) effector of the DIT of CAF rats.
Compartmental vascular changes in dogs after nephrectomy, DOCA, and saline: effect of nifedipine
Authors: Ogilvie Richard I. , Zborowska-Sluis Danuta
Published: April 2011

Hypertension (mean arterial pressure, (MAP) 131 ± 3 mmHg) developed in 18 dogs 4 weeks after left nephrectomy, deoxycorticosterone acetate (DOCA), 5 mg/kg sc twice weekly), and 0.5% NaCl drinking solution. This can be compared with MAP (95 ± 7 mmHg) of 13 dogs with nephrectomy alone and MAP (86 ± 4 mmHg) of 25 dogs without nephrectomy. The two-compartment model of the circulation revealed no differences in systemic vascular compliance, compartmental compliance, or flow distribution to the compartments. However, the time constant for venous return for the compartment with the rapid time constant was increased from 0.05 ± 0.004 min in control animals to 0.07 ± 0.006 min in the nephrectomy alone group and 0.09 ± 0.008 min in the hypertensive group (p < 0.001), as a result of an increase in venous resistance. Arteriolar resistance in this compartment was also increased in the hypertensive animals, as was the mean circulatory filling pressure and overall resistance to venous return. Nifedipine (0.025–0.05 mg/kg) reduced MAP by 15% in the nephrectomy alone group and by 22% in the hypertensive group, with reduction in arteriolar resistance only in the fast time constant compartment. In the slow time constant compartment, arteriolar resistance was increased by more than 100% and flow decreased by more than 50% after nifedipine. Unilateral nephrectomy, DOCA, plus NaCl resulted in hypertension by increasing arteriolar resistance in a vascular compartment with a fast time constant for venous return. Nifedipine countered this effect by inducing arteriolar vasodilation in this compartment. In addition, nifedipine reduced the mean circulatory filling pressure and overall resistance to venous return.
High affinity Ca2+–Mg2+ ATPase in the distal tubule of the mouse kidney
Authors: Brunette Michèle G. , Blouin Sylvie , Chan Meathan
Published: April 2011

The purpose of this study was to investigate whether Ca2+–Mg2+ ATPase in the distal tubule (where calcium transport is active, against a gradient, and hormone dependent) presents some characteristics different from those observed in the proximal tubule, and whether these characteristics are likely to shed light on the respective roles of this enzyme at the two sites of the nephron. The Ca2+- and Mg2+-dependent ATP hydrolysis was measured in microdissected segments of the distal nephron, the kinetic parameters were determined, and the influence of magnesium upon the sensitivity to calcium was examined. Results were compared with those obtained in the proximal tubule, and in purified membranes as reported by others. In the distal tubule, low concentrations of Mg2+ (< 10−7 M) did not influence ATP hydrolysis. At concentrations above 10−7 M, Mg2+ increased ATP hydrolysis according to Michaelis kinetics (apparent Km = 11.3 ± 2.4 μM, Vmax = 219 ± 26 pmol∙mm−1∙20 min−1). The addition of 1 μM Ca2+ decreased the apparent Km for Mg2+ and the Vmax for Mg2+. Similar results were obtained in the proximal tubule. At low Mg2+ concentrations, Ca2+ also stimulated ATP hydrolysis according to Michaelis kinetics with an apparent Km value for Ca2+ of 0.18 ± 0.06 and 0.10 ± 0.03 μM Ca2+ (ns) and a Vmax of 101 ± 12 and 89 ± 9 pmol∙mm−1∙20 min−1 (ns) in the distal and proximal tubules, respectively. In the two segments, the addition of Mg2+ strongly decreased the sensitivity to 1 μM Ca2+ so that at 1 mM Mg2+, the Ca2+-dependent ATPase activity was at the limit of detection. In conclusion, the kinetic parameters of the Ca2+- and Mg2+-dependent ATP hydrolysis were similar at the two sites of the nephron, and were also similar to those reported for the enzyme present in purified basolateral membranes. The nonadditive effect of the two cations Ca2+ and Mg2+ suggests that the two ATPase activities belong to the same enzyme, and this enzyme is the same in the proximal and distal tubules. Differences in Ca2+ transport characteristics should be attributed to factors other than variations in the nature of the Ca2+–Mg2+ ATPase.
In vivo apparent peptide-receptor dissociation rate constants for arginine vasopressin analogs estimated from inhibition of rat pressor responses
Authors: Gazis Diana
Published: April 2011

Apparent pressor receptor dissociation rate constants for arginine vasopressin, arginine vasotocin, oxytocin, oxypressin, and [1-deamino, 9-D-alanineamide]arginine vasopressin were estimated by the following method. Two minutes after injection of a moderate dose of agonist into urethane-anesthetized rats prepared for recording mean blood pressure, a large dose of inhibitor was injected. Under these conditions, in the first few moments after inhibitor injection, there should be no rebinding of the agonist after it dissociates, because vacant receptors should be immediately occupied by inhibitor. The rate of the blood pressure drop at the initiation of inhibition was calculated and used as an estimate of the dissociation rate of the agaonist. Apparent dissociation rate constants thus estimated were 1.1, 1.1, 6.9, 5.8, and 13.9 min−1 for arginine vasopressin, arginine vasotocin, oxytocin, oxypressin, and [1-deamino, 9-D-alanineamide]arginine vasopressin, respectively. These rate constants were inversely related to the pressor potencies (435, 250, 5, 3, and 0.7 U/mg, respectively) of these five compounds. Such a relationship is to be expected if decreased potency is in part due to a faster "off" rate from pressor receptors.
Anoxia reversibly suppresses neuronal calcium currents in rat hippocampal slices
Authors: Krnjević K. , Leblond Jean
Published: April 2011

Intracellular recording from CA1 neurons confirmed that short periods of anoxia (95% N2 + 5% CO2 for 2–4 min) have a hyperpolarizing action, caused by a rise in K conductance. After blockage of K channels with extracellular Cs+ and tetraethylammonium (or intracellular Cs+), large inward currents of Ca were evoked by depolarizing pulses: transient currents at a holding potential near −70 mV, and more sustained ones near −50 mV. Both types of Ca current were much reduced or fully suppressed after 1–3 min of anoxia, but they largely (or fully) recovered within 1–10 min of starting reoxygenation.
The comparative effects of feeding ammonium carbonate, ammonium sulfate, and ammonium chloride on urinary calcium excretion in the rat
Authors: Whiting Susan J. , Cole David E. C.
Published: April 2011

When either sulfate or chloride is added to the diet, the resulting acid load causes a rise in urinary calcium excretion. There is, however, the possibility that sulfate, which has been shown to complex renal tubular calcium, will further decrease renal calcium reabsorption and thus produce a greater calciuria than chloride. Because addition of a fixed cation (e.g., sodium) to the diet may also stimulate calciuresis, experiments were conducted using metabolizable ammonium to minimize cation effects. Ammonium salts of sulfate, chloride, and carbonate (control) were added to the diets of male rats at 0.3 mequiv./g weight of diet. Twenty-four hour excretion rates of calcium, sulfate, chloride, and net acid were measured at various intervals up to 1 month. As expected, the chloride and sulfate diets were both associated with significantly elevated urine calcium and net acid excretion as compared with controls. However, those fed sulfate exhibited significantly less calcium and acid excretion and absorbed a smaller proportion of the anion load than those given chloride. In a second experiment, the amounts of supplemental sulfate and chloride were adjusted so that total absorptions were similar. At 2 weeks, both calcium and acid excretions in the fixed anion groups were no longer significantly different. Thus, in chronic feeding trials, there appears to be no measurable difference in the calciuretic properties of sulfate and chloride anions.
Carboxyhemoglobinemia, polycythemia, cardiomegaly, and cardiovascular function in the anesthetized rat
Authors: Penney David G. , Baylerian Michael S.
Published: April 2011

The effects of carbon monoxide (CO), polycythemia (PC), and cardiomegaly (CM) on cardiovascular function were investigated in adult rats in which the latter two conditions were induced by 500 ppm CO inhalation for 5–6 weeks. Using an anesthetized open-chest preparation, these rats were compared with normal rats. With CO + PC + CM present, resting cardiac index, stroke index, stroke work, and minute work were elevated (heart rate also in the conscious state), while left ventricle end-diastolic pressure (LVDP) was normal. With PC + CM after CO washout, cardiac index and stroke index returned to normal at normal LVDP. Minute work, peripheral resistance, heart rate, and blood pressure, however, remained above normal. With CM alone, minute work, +dP/dtmax, +dF/dtmax, peripheral resistance, blood pressure, and LVDP declined from the condition with PC + CM. Although most cardiovascular parameters increased in the three conditions above with acutely increased LVDP, only with CM alone was performance augmentation normal. The results (i) reveal several characteristics of the hemodynamic response to chronic carboxyhemoglobinemia, (ii) suggest that the transient hypertension attending CO elimination in the presence of PC results from rapid reversal of peripheral vasodilatation, (iii) demonstrate decreased cardiac functional reserve with CO and (or) polycythemia upon preload challenge, and (iv) provide evidence for the benign nature of CO-induced cardiomegaly alone, on heart function.
Uitrastructural study of the effect of insulin dosage on the myocardium of spontaneously diabetic BB rats
Authors: McGrath Gail M. , McNeill John H.
Published: April 2011

Cardiac ultrastructure was studied in spontaneously diabetic BB rats maintained on two different regimens of insulin daily. For 3 months from the onset of overt diabetes, one diabetic group was well controlled with daily subcutaneous administration of sufficient insulin to prevent glycosuria (9.0–13.0 U/kg). Approximately half this dose (4.5 U/kg) of insulin was given daily to a second group of diabetic rats. Normal Wistar rats and nondiabetic BB rats were used as controls. Blood glucose values were three- to four-fold higher with respect to these controls in the diabetic BB rats receiving the smaller dose of insulin but were significantly lower than controls in diabetic animals receiving the higher insulin dose. A 30% difference in body weight with respect to the Wistar controls, obvious hyperliposis, and some nerve degeneration were seen in the low dose insulin group of diabetics. Such changes did not occur in the well-controlled insulin-treated group. Electron microscopic examination of the left ventricular tissue revealed mild damage in both groups of diabetics consisting of small focal lesions and mild edema along the sarcoplasmic reticulum and sometimes adjacent to the sarcolemma. Thus, insulin treatment, which prevented glycosuria, resulted in normal tissue lipid levels and prevented nerve damage but had little effect on the other diabetes-induced ultrastructural alterations in the myocardium of these rats.
Effect of hepatic venous sphincter contraction on transmission of central venous pressure to lobar and portal pressure
Authors: Lautt W. Wayne , Legare Dallas J. , Greenway Clive V.
Published: April 2011

In dogs anesthetized with pentobarbital, central vena caval pressure (CVP), portal venous pressure (PVP), and intrahepatic lobar venous pressure (proximal to the hepatic venous sphincters) were measured. The objective was to determine some characteristics of the intrahepatic vascular resistance sites (proximal and distal to the hepatic venous sphincters) including testing predictions made using a recent mathematical model of distensible hepatic venous resistance. The stimulus used was a brief rise in CVP produced by transient occlusion of the thoracic vena cava in control state and when vascular resistance was elevated by infusions of norepinephrine or histamine, or by nerve stimulation. The percent transmission of the downstream pressure rise to upstream sites past areas of vascular resistance was elevated. Even small increments in CVP are partially transmitted upstream. The data are incompatible with the vascular waterfall phenomenon which predicts that venous pressure increments are not transmitted upstream until a critical pressure is overcome and then further increments would be 100% transmitted. The hepatic sphincters show the following characteristics. First, small rises in CVP are transmitted less than large elevations; as the CVP rises, the sphincters passively distend and allow a greater percent transmission upstream, thus a large rise in CVP is more fully transmitted than a small rise in CVP. Second, the amount of pressure transmission upstream is determined by the vascular resistance across which the pressure is transmitted. As nerves, norepinephrine, or histamine cause the hepatic sphincters to contract, the percent transmission becomes less and the distensibility of the sphincters is reduced. Similar characteristics are shown for the "presinusoidal" vascular resistance and the hepatic venous sphincter resistance. Finally, a unit of pressure rise in downstream pressure will be more completely transmitted upstream as the basal starting downstream pressure is increased. These data fulfill the predictions of the distensible hepatic venous sphincter model developed for the cat liver and are incompatible with the Starling resistor – vascular waterfall theory. The distensible hepatic venous resistance allows the splanchnic blood volume to most efficiently buffer the largest changes in CVP by transmitting proportionately more pressure to the highly compliant splanchnic vessels. In addition the distensible sphincters serve to autoregulate portal venous pressure. As portal flow changes, the passively distensible sphincters minimize changes in PVP.
Renal medullary plasma flow rate and reabsorption of salt and water from inner medullary collecting duct
Authors: Cupples W. A. , Sonnenberg H.
Published: April 2011

It has been proposed that medullary washout secondary to increased blood flow will limit maximal urine osmolality and reabsorption of salt and water from the inner medullary collecting duct. We have tested this prediction. The function of the inner medullary collecting duct was examined by microcatheterization. Acetylcholine was infused directly into the renal circulation, captopril was infused intravenously, and angiotensin II was infused into the renal circulation in rats which also received captopril. Medullary plasma flow rate, measured by dye–dilution in parallel experiments, was not significantly increased by acetylcholine; it was increased 30% (p < 0.02) by systemic infusion of captopril, and was returned to control by angiotensin II. Acetylcholine increased both urine flow rate and sodium excretion (p < 0.01, p < 0.001, respectively), while captopril increased only sodium excretion (p < 0.025). Angiotensin II blocked the natriuresis due to captopril. None of the treatments altered urine osmolality (p > 0.4 in all cases). Acetylcholine increased the loads of water, sodium, chloride, and total solute delivered to the inner medullary collecting duct. Angiotensin II reduced delivery of water and solutes compared with captopril alone. None of the treatments affected load dependency of reabsorption of water, sodium, chloride, or total solute in the inner medullary collecting duct. We conclude that there is, at most, a weak interaction between medullary blood flow and reabsorption from the inner medullary collecting duct.
Interdigestive intestinal motility in dogs with chronic exclusion of bile from the digestive tract
Authors: Plourde Victor , Trudel Louise , Poitras Pierre
Published: April 2011

To elucidate the role of bile delivery into the duodenum on the regulation of plasma motilin and on the interdigestive migrating complex, three dogs were operated upon to ligate the main bile duct and divert the biliary flow into the urinary bladder via a Foley catheter. After the operation, despite the chronic diversion of bile from the digestive tract, all animals maintained an excellent health status and exhibited recurrent periods of phase III motor activity migrating from the duodenum to the ileum, which were associated with cyclic increases in plasma motilin. Following the infusion of pooled dog bile (1 mL/min for 10 min) into the duodenum, a premature phase III and a concomitant rise in plasma motilin were observed. These results suggest, that although bile delivery into the duodenum can induce motilin increase in plasma and period of phase III activity in the gut, this phenomenon does not constitute an essential stimulus for the release of motilin and for the induction of the phase III of the interdigestive migrating complex.
Prejunctional α2-adrenergic properties of S-3341 (dicyclopropylmethyl)amino-2-Δ-2-oxazoline: a comparison with clonidine
Authors: Bourreau Jean-Pierre , Tricoche Robert
Published: April 2011

The prejunctional activities of S-3341 and clonidine have been studied in the transmural field-stimulated epididymal part of the rat vas deferens. Both S-3341 and clonidine inhibited these neuronally induced contractions. At high concentrations, these agonists induced spontaneous contractions in the preparation, which were abolished by 10−7 M prazosin. The inhibitory effects of S-3341 and clonidine were antagonized in a competitive manner by rauwolscine and were found not to be modified in a statistically significant manner by 10−7 M prazosin. The pA2 values of rauwolscine against S-3341 and clonidine were the same, indicating the receptors influenced by these drugs were the same also. However, the efficacy of S-3341 is lower than that of clonidine (by a factor of approximately 100). This lower efficacy of S-3341 at the prejunctional level could be linked to the lack of a sedative effect of this compound at therapeutic concentrations.
Evidence of digoxin metabolism by the kidney
Authors: Koren Gideon , Klein Julia , Silverman Melvin
Published: April 2011

By performing single pass experiments in the dog, we could identify by thin layer chromatography a digoxin metabolite produced by the kidney. In vitro studies verify that this new species is produced by the brush border membrane of the renal tubular cell.
Left ventricular reflex control of venous return and systemic vascular capacitance in dogs
Authors: Hoka Sumio , Bosnjak Zeljko J. , Seagard Jeanne L. , Siker Daniel , Palmisano Barbara W. , Coon Robert L. , Kampine John P.
Published: April 2011

The reflex effects of left ventricular distension on venous return, vascular capacitance, vascular resistance, and sympathetic efferent nerve activity were examined in dogs anesthetized with sodium pentobarbital. In addition, the interaction of left ventricular distension and the carotid sinus baroreftex was examined. Vascular capacitance was assessed by measuring changes in systemic blood volume, using extracorporeal circulation with constant cardiac output and constant central venous pressure. Left ventricular distension produced by balloon inflation caused a transient biphasic change in venous return; an initial small increase was followed by a late relatively large decrease. Left ventricular distension increased systemic blood volume by 3.8 ± 0.6 mL/kg and decreased systemic blood pressure by 27 ± 2 mmHg (1 mmHg = 133.3 Pa) at an isolated carotid sinus pressure of 50 mmHg. These changes were accompanied by a simultaneous decrease in sympathetic efferent nerve activity. When the carotid sinus pressure was increased to 125 and 200 mmHg, these responses were attenuated. It is suggested that left ventricular mechanoreceptors and carotid baroreceptors contribute importantly to the control of venous return and vascular capacitance.
Further evidence for a hypothalamic site of action of atrial natriuretic factor: inhibition of prolactin secretion in the conscious rat
Authors: Samson Willis K. , Bianchi Renee
Published: April 2011

The presence of atrial natriuretic factor (ANF) in the hypothalamus and pituitary gland suggests a possible neuroendocrine action of the peptide. Because ANF has been shown to alter the activity of hypothalamic neurons and to interact with brain dopamine systems, we examined the possibility that it might be involved in the hypothalamic control of prolactin (PRL) and thyroid-stimulating hormone (TSH) secretion. Neither basal not stimulated release of PRL or TSH from cultured dispersed anterior pituitary cells was altered by doses of ANF ranging from 10−11 to 10−6 M. Similarly, the in vitro inhibition of PRL release by dopamine was not affected by the presence of ANF (10−7 M). Plasma levels of PRL and TSH in conscious male rats infused for 30 min with 0.01 or 0.1 μg ANF∙kg–1∙min–1 did not differ significantly from those present in saline infused controls. Third-cerebroventricular injection of saline (2 μL) or saline plus ANF (0.02, 0.1, 1.0, or 2.0 nmol) did not significantly alter TSH secretion; however, injection of the two highest doses of ANF resulted in significant inhibition of PRL release. Levels of PRL remained significantly reduced for 90 min after injection of 2 nmol ANF. The results indicate that ANF can act centrally to alter the release of neural factors responsible for the hypothalamic control of lactotroph function.
Models of sensorimotor transformations and vestibular reflexes
Authors: Baker J. F. , Banovetz J. M. , Wickland C. R.
Published: April 2011

The vestibulo-ocular and vestibulo-collic reflexes are well-studied sensorimotor systems with dynamic properties that have been successfully modeled. Recently proposed matrix and tensorial models attempt to describe the spatial organization of these reflexes in three dimensions. Here we describe experiments that test these models. We show that a matrix model of the vestibulo-ocular reflex provides a satisfactory description of its spatial properties. The vestibulo-collic reflex is more complex, but a tensorial model makes close predictions of neck muscle excitation by the vestibulo-collic reflex. In addition, our preliminary data show that the cervico-collic or neck stretch reflex produces essentially the same spatial pattern of neck muscle excitation as the vestibulo-collic reflex, a finding predicted by the tensorial model. We conclude by showing electromyographic and single neuron responses that can be modeled only by combining models of dynamics with models of spatial organization. We believe that the development of such models is the next major challenge in the application of quantitative methods to analysis of reflex behavior.
Effects of carbohydrate and protein administration on rat tryptophan and 5-hydroxytryptamine: differential effects on the brain, intestine, pineal, and pancreas
Authors: Teff Karen L. , Young Simon N.
Published: April 2011

We compared the acute effects of intragastric administration of protein and carbohydrate on tryptophan and 5-hydroxytryptamine (5HT) in rat brain, pineal, intestine, and pancreas. Protein decreased and carbohydrate increased brain indoles relative to water-infused controls. These effects were due to competition between the large neutral amino acids for entry into the brain. This competition does not exist in the pineal. The macronutrients had no effect on pineal tryptophan metabolism. In the intestine, protein resulted in higher tryptophan levels as compared to controls, owing to absorption of tryptophan in the protein. However intestinal 5HT levels were influenced by factors other than precursor availability. Pancreatic indoles were affected in a similar manner to the brain indoles. Competition between the large neutral amino acids for entry into the pancreas was also indicated by the finding that valine administration lowered brain and pancreatic tryptophan, but not the levels in the intestine and pineal. It remains to be seen whether the decrease in pancreatic 5HT after a protein meal and the increase after carbohydrate modulate the release of insulin and glucagon.
Effect of sinus node on spontaneous release of atrial natriuretic peptide in isolated atria
Authors: Wong Norman L. M. , Wong Eric F. C. , Au Gong H. , Hu David C. K. , Qi Anzhen , Kerr Charles
Published: April 2011

Experiments were conducted to examine the release of atrial natriuretic peptede (ANP) in an isolated atrium in the presence and absence of sinus node tissue. The first series of experiments were conducted with the aid of a metabolic chamber to examine the spontaneous release of ANP by the right atrium with and without the sinus node region. The left atrium was also studied. The right atrium with the sinus node, quiescent right atrium without the sinus node, and the left atrium were incubated at 35 °C in 10 mL of oxygenated Tyrode's solution. After 40 min of equilibration, the incubation medium was removed at 10-min intervals for the determination of immunoreactive ANP concentration. The right atria with the sinus node released the highest amount of ANP into the incubation medium (32.2 ± 2.7 pg∙min−1∙mg−1), compared with quiescent right atria (20.9 ± 3.7 pg∙min−1∙mg−1). The left atria released the least amount of ANP into the incubation medium (9.9 ± 1.5 pg∙min−1∙mg−1) when compared with the quiescent right atria and the right atria. In the second series of experiments, the right atrium was divided into the sinus node region and the quiescent right atrium, and these tissues were studied in paired fashion with a modified Langendorff preparation. The right atrium without the sinus node and sinus node region were perfused with Tyrode's solution, equilibrated with 95% O2 and 5% CO2 at 37 °C with a constant flow of 0.5 mL/min. Spontaneous release of ANP was significantly higher from the sinus node region (11.2 ± 0.6 pg∙mL−1∙min−1) than the quiescent right atria (7.22 ± 0.9 pg∙mL−1∙min−1). Tissue analysis was also performed in these experiments to determine the distribution of ANP within the atria. Our results indicated that the sinus node region (0.31 ± 0.03 μg/mg) contained less ANP than the quiescent right atria (0.43 ± 0.04 μg/mg). Although the amount of ANP in the quiescent right atria surpassed that in the sinus node region, the sinus node region released more ANP. These results suggested that the sinus node may play a major role in the release of ANP.