bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal and hormonal responses to prolonged atrial stretch
Authors: Kaufman S.
Published: December 2017

The relationship between prolonged (6 h) atrial stretch, urine output, and plasma atrial natriuretic factor (ANF) was investigated in conscious rats. On inflation of a balloon at the superior venal caval-right atrial junction, urine volume and sodium output increased. However, this renal response was no longer apparent after the first hour, and there were no further changes in urine output when the balloon was deflated. This transient renal response was most marked during the first 30 min of balloon inflation, at which time plasma ANF was also elevated. At 6 h, plasma ANF was still elevated, although urine output had, by then, returned to normal. On deflation of the balloon, plasma ANF levels returned to normal. It is clear that the renal and hormonal responses to atrial stretch may be temporally uncoupled. This probably reflects adaptation of the atrial volume receptors in the absence of such an effect on ANF release. Although this might be interpreted to mean that ANF is not of physiological importance in fluid and electrolyte balance, a more plausible explanation is that ANF needs the backing of the reflex pathways arising from stimulation of the atrial receptors to express its natriuretic activity.
Turnover of serotonin in brain of an anoxia-tolerant vertebrate, the crucian carp
Authors: Nilsson G. E.
Published: December 2017

Serotonin (5-HT) is a neurotransmitter in the vertebrate brain. Estimates of 5-HT turnover times range between 1 h (mammals) and 10 h (goldfish). Synthesis and catabolism of 5-HT are dependent on molecular oxygen, hence, 5-HT turnover comes to a halt during anoxia. Nevertheless, a few vertebrates, such as the crucian carp (Carassius carassius L.), tolerate anoxia for several weeks. To assess the ability of the crucian carp brain to tolerate a stop in 5-HT turnover during anoxia, it is essential to know its normoxic rate of 5-HT turnover. The turnover of 5-HT was estimated in different brain regions of winter-acclimatized crucian carp held in normoxia at 8 degrees C using two different methods, i.e., 1) by measuring the increase seen in 5-HT after monoamine oxidase inhibition (by pargyline), and 2) by measuring the rate of 5-hydroxytryptophan (5-HTP) accumulation, after the conversion of 5-HTP to 5-HT had been inhibited (by N-m-hydroxybenzylhydrazine). Both methods suggested similar turnover rates (approximately 10-20 pmol/g h) and turnover times (1-3 days). This is probably the slowest 5-HT turnover ever measured in a vertebrate (less than 1/100 of that of mammals). The slow 5-HT turnover could be explained by a high degree of recycling of the same 5-HT molecules, in combination with a decreased turnover at low temperatures. Moreover, the slow 5-HT turnover might be a prerequisite for preserving the functional integrity of the 5-HT system during anoxia.
Baroreflex control of sympathetic outflow in pregnant rats: effects of captopril
Authors: Crandall M. E. , Heesch C. M.
Published: December 2017

Arterial baroreflex control of renal sympathetic nerve activity (RSNA) was compared in nonpregnant (NP) and near-term pregnant (P) chloralose-anesthetized rats. Baroreflex curves were obtained by recording reflex changes in RSNA (expressed as a percent of base line) due to increases and decreases in mean arterial pressure (MAP) [intravenous phenylephrine and nitroprusside (NTP)]. The slope, midpoint (EP50), and threshold pressures of the baroreflex curves were compared. Base-line MAP was significantly lower in the pregnant animals (P = 96 +/- 3 vs. NP = 113 +/- 5 mmHg). The baroreflex curves of pregnant animals also had significantly lower threshold (P = 95 +/- 3 vs. NP = 110 +/- 5 mmHg) and midpoint values (P = 105 +/- 4 vs. NP = 119 +/- 5 mmHg). The response to unloading the baroreceptors was attenuated in the pregnant animals as indicated by a decrease in slope of the NTP portion of the baroreflex curve (P = 0.95 +/- 0.17 vs. NP = 1.61 +/- 0.29% nerve activity/mmHg). Responses to blockade of angiotensin-converting enzyme with captopril (2 mg/kg iv) were also examined. There were no differences in EP50 or slope among the control, captopril, and recovery baroreflex curves within either the nonpregnant or pregnant animals. However, after captopril, MAP decreased to a greater extent in the pregnant rats, yet RSNA increased to the same level for the two groups. Thus pregnancy results in a leftward shift of the baroreflex function curve toward a lower operating pressure range. In addition, pregnant rats demonstrated an impaired ability to increase sympathetic outflow above base-line values in response to a hypotensive challenge.
Area postrema: essential for support of arterial pressure after hemorrhage in rats
Authors: Skoog K. M. , Blair M. L. , Sladek C. D. , Williams W. M. , Mangiapane M. L.
Published: December 2017

Previous studies have indicated that the area postrema (AP) of the rat is necessary for the development of chronic angiotensin-dependent hypertension. The present study assesses the role of the AP in the maintenance of arterial pressure during hemorrhage. Sprague-Dawley rats were given sham or AP lesions 1 wk before the experiment. They were instrumented with femoral arterial and venous catheters 2 days before the experiment. On the day of the experiment, base-line mean arterial pressure (MAP) was measured for 1 h before hemorrhage. During the following 45 min, each rat was subjected to one 7-ml/kg hemorrhage every 15 min for a total of three hemorrhages. MAP was monitored by computerized data acquisition. As shown previously, MAP was slightly but significantly lower in AP-lesion rats compared with sham-lesion rats before the hemorrhage procedure. In AP-lesion rats, hemorrhage resulted in a significantly greater fall in arterial pressure than in sham-lesion rats. In spite of larger drops in pressure in AP-lesion rats, hemorrhage caused equivalent increases in plasma renin and vasopressin in both groups. In AP-lesion rats compared with sham-lesion rats, significant bradycardia was present before hemorrhage. Hemorrhage caused bradycardia in both sham- and AP-lesion rats relative to the prehemorrhage heart rates, but AP-lesion rats showed greater bradycardia than did sham-lesion rats during every time period. We conclude that the AP may play an important role in the defense of arterial pressure against hemorrhage.
Intraduodenal infusions of fats elicit satiety in sham-feeding rats
Authors: Greenberg D. , Smith G. P. , Gibbs J.
Published: December 2017

The satiating effect of duodenally administered fats was investigated with intraduodenal infusions of Intralipid in sham-feeding rats. Intralipid rapidly inhibited sham feeding and elicited the behavioral sequence of satiety. The satiating potency of Intralipid infusions in concentrations of 0.125-1 kcal/ml was a function of the concentration infused. The time course for Intralipid-induced satiety showed that fats inhibited feeding and led to the behavioral sequence of satiety within 15 min after the infusions began. This time course is evidence for a preabsorptive site of action to the small intestine. To test this hypothesis we added the local anesthetic tetracaine to Intralipid infusions. Tetracaine significantly reduced the satiating potency of Intralipid infusion. This result supports the hypothesis of a preabsorptive site of action. We also tested the specificity of intraduodenal Intralipid for feeding by administering Intralipid to rats that were sham drinking. The effect of Intralipid was relatively specific because the threshold concentration of Intralipid necessary to inhibit sham drinking was higher than the threshold for sham feeding. In addition, at superthreshold concentrations, Intralipid inhibited sham drinking less than sham feeding and elicited different behaviors than were observed during sham feeding.
Site of action of putative lipostatic factor: food intake and peripheral pentose shunt activity
Authors: Harris R. B. , Martin R. J.
Published: December 2017

Obesity due to overfeeding in one parabiotic rat results in mild hypophagia and specific loss of fat from its partner. Studies were conducted to determine whether the changes in body composition were reversible and whether the nonsignificant reduction in food intake was a primary response to a humoral lipostatic factor. Tube feeding partners of overfed rats 0.5 g more food per day than eaten voluntarily prevented loss of fat, although hepatic and adipose glucose-6-phosphate dehydrogenase activities were depressed. Glucose flux through the pentose phosphate pathway was inhibited in both adipose and hepatic tissue from thin partners of obese rats, although fatty acid synthesis was depressed only in adipose tissue. Response to insulin by adipocytes from ad libitum partners of obese rats appeared to be blunted, but insulin sensitivity was normal. When overfeeding stopped, both partners returned to control body composition, suggesting that the changes observed in parabiotic partners of obese rats were physiological responses to a putative circulating lipostatic factor rather than a nonspecific consequence of parabiosis.
Atrial natriuretic factor modulates whole kidney tubuloglomerular feedback
Authors: Margulies K. B. , Burnett J. C.
Published: December 2017

Increases in sodium delivery to the distal nephron reduce glomerular filtration rate (GFR) via tubuloglomerular feedback (TGF). Central volume expansion and pharmacological concentrations of atrial natriuretic factor (ANF) are known to attenuate this response. To test the hypothesis that whole kidney TGF is attenuated by pathophysiological concentrations of ANF, hypertonic saline was given intrarenally in five dogs receiving an intravenous infusion of synthetic ANF at 20 ng.kg-1.min-1. To examine whole kidney TGF responses in heart failure, six additional dogs with acute congestive heart failure induced by rapid ventricular pacing also received intrarenal hypertonic saline. Seven sham-paced dogs served as controls. An isolated increase in circulating ANF from 26 +/- 3 to 342 +/- 23 pg/ml abolished the whole kidney GFR response to hypertonic saline. In acute congestive heart failure, the GFR response to hypertonic saline was not attenuated despite acute central volume overload and similar increases in circulating ANF. This intact response to hypertonic saline in acute congestive heart failure may contribute to the renal sodium retention characteristic of congestive heart failure.
Presynaptic modulation of ganglionic ACh release by muscarinic and nicotinic receptors
Authors: Dujic Z. , Roerig D. L. , Schedewie H. K. , Kampine J. P. , Bosnjak Z. J.
Published: December 2017

The present experiments were undertaken to investigate the effects of atropine and d-tubocurarine on acetylcholine (ACh) release and ganglionic synaptic transmission in the isolated cat stellate ganglion. Ganglionic release of picomole amounts of ACh was measured by radioenzymatic assay, and ganglionic transmission was estimated on the basis of the compound action potential recorded from the postganglionic stellate cardiac nerve. Atropine (5 microM) produced a significant increase in both spontaneous and evoked ACh release from the ganglion while depressing synaptic transmission. d-Tubocurarine (20 microM) also caused a significant, though smaller, increase in spontaneous release of ACh but had little effect on evoked release of ACh. These results suggest that ACh release and synaptic transmission in the cat stellate ganglion are subject to cholinergic feedback regulation, which appears to be mediated predominantly via muscarinic presynaptic receptors.
Avian basal metabolic rates: their association with body composition and energy expenditure in nature
Authors: Daan S. , Masman D. , Groenewold A.
Published: December 2017

Measurements of basal metabolic rate (BMR), body water, fat, and lean dry mass of different organs were obtained in 22 bird species, ranging from 10.8 to 1,253 g body mass. Residuals of BMR (after subtracting BMR allometrically predicted from body mass) were positively correlated with residuals of lean dry heart and kidney mass. Measurements of both BMR and the daily energy expenditure of parent birds (DEEpar) during the period of nestling care as assessed by labeled-water turnover were collected from the literature for 26 altricial bird species. The allometric relationships with body mass in this data set were: log BMR (W) = -1.385 + 0.684 log mass (g) [fraction of variance (r2) = 0.973] and log DEEpar (W) = -0.797 + 0.659 log mass (g) (r2 = 0.967). Residuals of log BMR and log DEEpar were positively correlated with each other. The parallel regressions and correlation of residuals lead to reduced variance in the ratio of BMR/DEEpar (mean 0.301; SD 0.086). We suggest that natural selection has led to an adjustment of the size of organs (such as heart and kidney) involved in sustaining energy metabolism at the DEE maximized during parental care and that size-independent variation in BMR reflects the relative size of this highly metabolically active machinery. These relationships of BMR lead to new interpretations of the decline in mass-specific BMR with increasing body size and decreasing latitude and of the difference in mass-specific BMR between birds and mammals.
Armenian hamster female protein: a pentraxin under complex regulation
Authors: Coe J. E. , Ross M. J.
Published: December 2017

The serum of Armenian hamster (Cricetulus migratorius) contains a protein homologous to female protein (FP) that has been characterized in the Syrian (golden) hamster. Of unknown function, FP belongs to a family of proteins (called pentraxins) that have a common ancestral gene and are widely expressed in nature. Whereas serum concentration of FP in Syrian hamsters (SFP) is many fold greater (200- to 300-fold) in females vs. males, Armenian hamster FP (AFP) is only moderately elevated (approximately 3-fold) in female vs. males and only for the fall-winter months of the year. In the Armenian hamster testosterone administration to females or castration of males has no effect on AFP serum levels, whereas in Syrian hamster these treatments change SFP serum concentration to that characteristic of the opposite sex. Some sex steroid control of hepatic AFP synthesis is evident, however, as serum levels decrease after exogenous estrogen treatment. In contrast to Syrian hamster FP, normal levels of AFP are dependent on an intact hypophysial-pituitary axis and also are influenced by the season of the year. As an acute-phase protein, AFP responds in a typical fashion, with increasing serum levels detected in both sexes in contrast to the divergent sex-limited response in Syrian hamsters. Although AFP and SFP are similar structurally, morphologically, and antigenetically and share common binding specificities, the regulation of FP synthesis in Armenian hamster is very different from that previously found in Syrian hamster.
Microinjection of substance P and ACh into rat intermediolateral nucleus elicits cardiovascular responses
Authors: Calaresu F. R. , McKitrick D. J. , Weernink E. J.
Published: December 2017

The effects of substance P (SP) or acetylcholine (ACh) microinjected into the intermediolateral nucleus of the spinal cord (IMLn) on arterial pressure (AP) and heart rate (HR) were investigated in 22 male Wistar rats under urethan and artificial ventilation. L-Glutamate (Glu) was microinjected into the IMLn between C7 and T4 to locate cardiovascular sites. Micropipettes containing Glu were stereotaxically positioned in 82 histologically verified sites in the IMLn between C7 and T4 on both the right and left sides. Microinjection of 4-10 nl of 0.18 M Glu in 30 of 39 explored sites at the T2 level elicited significant increases in HR (+24.2 +/- 3.1 beats/min). These changes were accompanied by significant increases in mean AP (+11.4 +/- 1.2 mmHg) at the T2 level (32/47 sites). Microinjection of 4-10 nl of SP (3 X 10(-7) to 3 X 10(-4) M) or ACh (0.005-0.5 M) in the right IMLn at the T2 level elicited increases in HR but did not affect AP. The duration of the responses to SP or ACh was significantly longer than the duration of the responses to Glu. The responses to ACh could be blocked by prior microinjection of 5 X 10(-2) M atropine. No responses were ever obtained in the left IMLn by microinjection of Glu, SP, or ACh. These results support the hypothesis that Glu, ACh, and SP mediate sympathoexcitation in the IMLn of the rat and that these excitatory responses have different temporal patterns.
Noradrenergic and neuropeptide Y mechanisms in guanethidine-sympathectomized rats
Authors: Benarroch E. E. , Schmelzer J. D. , Ward K. K. , Nelson D. K. , Low P. A.
Published: December 2017

The cardiovascular responses to sympathomimetic agents, the norepinephrine (NE) content in peripheral tissues, and the tissue content and cardiovascular effects of neuropeptide Y (NPY) were examined in anesthetized adult rats with guanethidine-induced sympathectomy (GuSx). We observed blunted pressor responses to tyramine, exaggerated pressor responses to phenylephrine, and markedly reduced NE contents in the atrium, femoral artery, superior cervical ganglion (SCG), and sciatic and vagus nerves. When tyramine responses were corrected for the NE content in the SCG, GuSx rats were similar to controls. A depletion of NPY levels in tissue resulted in an increased sensitivity to the pressor effects of intravenous NPY administration. GuSx, therefore, reproduces findings of postganglionic adrenergic failure in humans. Responses to the administration of sympathomimetic agents may reflect the degree of noradrenergic denervation. NPY may be a potential marker of chronic postganglionic sympathetic denervation in cardiovascular tissue.
Growth regulation of the vascular system: evidence for a metabolic hypothesis
Authors: Adair T. H. , Gay W. J. , Montani J. P.
Published: December 2017

Prolonged imbalances between the perfusion capabilities of the blood vessels and the metabolic requirements of the tissue cells often lead to modification of the vasculature to satisfy the tissue needs. This homeostatic response appears to be bidirectional, since the vascularity of a tissue can increase or decrease in parallel with primary changes in metabolic rate. The factors that mediate the responses are not well understood, but oxygen has been implicated as a major control element, since vessel growth increases during hypoxic conditions and decreases during hyperoxic conditions. The following feedback control hypothesis may apply to many different physiological situations. Decreased oxygenation causes the tissues to become hypoxic, and this initiates a variety of signals that lead to the growth of blood vessels. The increase in vascularity promotes oxygen delivery to the tissue cells by decreasing diffusion distances, increasing capillary surface area, and increasing the maximum rate of blood flow. When the tissues receive adequate amounts of oxygen even during periods of peak activity, the intermediate effectors return to normal levels, and this negative signal, in turn, stops the further development of the vasculature. Although the effector mechanisms of the hypoxic stimulus are still being investigated, adenosine, which is produced in hypoxic tissues, appears to mediate hypoxia-induced increases in vascularity in some instances. Roles for fibroblast growth factor as well as mechanical factors associated with vasodilation and increased blood flow are postulated. Although blood vessel growth is a multifactorial process, a major influence in its regulation appears to be metabolic need. If this view is correct, it may be found that many of the quantitatively significant factors that control growth in a given vasculature are themselves modulated or controlled by metabolic signals reflecting the nutritional status of the tissues which that vasculature supplies.
Hypothalamic adrenoceptors mediate sympathoadrenal activity in exercising rats
Authors: Scheurink A. J. , Steffens A. B. , Gaykema R. P.
Published: December 2017

The role of hypothalamic adrenoceptors in the exercise-induced alterations of plasma norepinephrine (NE), epinephrine (E), and corticosterone concentrations was investigated in rats. Exercise consisted of strenuous swimming against a counter-current for 15 min. Before, during, and after swimming, blood samples were withdrawn through a permanent heart catheter for determination of E, NE, and corticosterone. In control rats E, NE, and corticosterone levels were all increased during exercise. Infusion of the alpha-adrenoceptor antagonist phentolamine through permanent bilateral cannulas into the ventromedial hypothalamus (VMH) immediately before exercise reduced the exercise-induced increase in plasma E without affecting NE. Infusion of the beta-adrenoceptor antagonist timolol into the VMH enhanced plasma E and attenuated plasma NE increases. Infusion of phentolamine into the lateral hypothalamic area (LHA) led to enhanced NE and unchanged E concentrations, whereas infusion of timolol into the LHA caused a potentiation of the increase in plasma E without an effect on NE. Plasma corticosterone concentrations were not affected. The results suggest that 1) alpha- and beta-adrenoceptors in the hypothalamus influence peripheral catecholamine release, and 2) E and NE responses to exercise can be dissociated by interference of the central nervous system.
Discharge patterns of ventrolateral medullary neurons during muscular contraction
Authors: Bauer R. M. , Iwamoto G. A. , Waldrop T. G.
Published: December 2017

Static muscular contraction is known to elicit reflex increases in arterial pressure. However, the areas of the central nervous system that mediate this reflex remain elusive. A recent study from this laboratory suggested that neurons in the ventrolateral medulla (VLM) participate in the pressor reflex to muscular contraction. In the present study, we sought to ascertain whether extracellular single-unit activity of VLM neurons is altered by static contraction of hindlimb muscles. In anesthetized cats, muscular contraction elicited by stimulation of L7 and S1 ventral roots evoked increases in arterial pressure, heart rate, and minute ventilation. The firing frequency in 33 of 50 VLM units increased greater than 70% during muscular contraction. VLM units displayed two types of discharge patterns in response to contraction: 1) a rapid onset response (0.5-3 s) and 2) a delayed onset response (10-20 s). Computer averaging analysis showed that 14 of 28 VLM units tested had a cardiac-related rhythm and 10 of those 14 also responded to muscular contraction. Muscular contraction had no effect on the discharge patterns of most neurons located outside the VLM. These findings suggest that neurons in the ventrolateral medulla respond to muscular contraction and may have a role in the pressor reflex to muscular contraction.
Role of vasopressin in renal vascular changes with hypoxemia and hypercapnic acidosis in conscious dogs
Authors: Rose C. E. , Ragsdale N. V. , Carey R. M.
Published: December 2017

To evaluate the role of vasopressin in the renal changes during combined acute hypoxemia and acute hypercapnic acidosis, eight conscious female mongrel dogs prepared with controlled sodium intake at 80 meq/24 h for 4 days were studied in one of the following six protocols: acute hypoxemia (80 min, arterial PO2 34 +/- 1 mmHg) followed by combined acute hypoxemia and hypercapnic acidosis (40 min, arterial PO2 35 +/- 1 mmHg, arterial PCO2 58 +/- 1 mmHg, pH = 7.20 +/- 0.01) during 1) intrarenal vehicle at 0.5 ml/min (N = 8); or 2) intrarenal infusion of vasopressin V1-receptor antagonist [d(CH2)5Tyr(Me)]AVP at 5 ng.kg-1.min-1 (N = 5); and with normal gas exchange during 3) intrarenal vasopressin at 0.05 mU.kg-1.min-1 (N = 8); 4) simultaneous infusion of intrarenal vasopressin and [d(CH2)5Tyr(Me)]AVP, 5 ng.kg-1.min-1 (N = 4); 5) intrarenal [d(CH2)5Tyr(Me)]AVP, 5 ng.kg-1.min-1 (N =4); and 6) intrarenal vehicle at 0.5 ml/min (N = 7). Intrarenal infusion of a subpressor dose of vasopressin resulted in a transient decrease in glomerular filtration rate and effective renal plasma flow over the first 20 min of infusion, suggesting that vasopressin induced nonsustained vasoconstriction of the renal vasculature. Intrarenal administration of [d(CH2)5Tyr-(Me)]AVP failed to block the fall in glomerular filtration rate or effective renal plasma flow when renal arterial blood vasopressin levels were elevated by intrarenal administration of exogenous vasopressin or by elevated systemic arterial endogenous circulating vasopressin during combined acute hypoxemia and hypercapnic acidosis. These data suggest that vasopressin (V1-receptor stimulation) does not play an important role in the renal vasoconstriction during combined acute hypoxemia and hypercapnic acidosis in conscious dogs.
Acute phase response to endotoxin: rise in plasma alpha-MSH and effects of alpha-MSH injection
Authors: Martin L. W. , Lipton J. M.
Published: December 2017

Endotoxins, cell wall components of bacteria, cause a number of biological effects, presumably via induction of potent cytokines. Previous research suggests that the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) and its COOH-terminal tripeptide reduce the effects of cytokines. These molecules evoke antipyretic and anti-inflammatory effects in vivo. Localization of alpha-MSH within lymphocytes and recent observations that alpha-MSH receptors are widespread and that circulating alpha-MSH increases after systemic injection of endogenous pyrogen, a cytokine-containing extract, suggest that the peptide modulates host defense reactions. One aim of the present experiments was to learn whether a rise in circulating alpha-MSH occurs in synchrony with aspects of the acute phase response (APR) in conscious rabbits given endotoxin. A second aim was to learn whether administration of a single large dose of alpha-MSH inhibits all aspects of the APR induced by a low dose of endotoxin. The results indicate that the concentration of circulating alpha-MSH in rabbits does increase along with other changes in the APR (e.g., increase in corticosterone), which suggests that the peptide is widely available to modulate cytokine effects after endotoxin. Contrary to expectations based on previous results, a large dose of the peptide given intravenously inhibited only fever and not other aspects of the APR. The results suggest that the rise in circulating alpha-MSH is an aspect of the APR and that an acute increase in the circulating peptide caused by intravenous injection does not inhibit all other aspects of the host response to endotoxin.
Mechanoreceptor modulation of endogenous respiratory rhythms in vertebrates
Authors: Milsom W. K.
Published: December 2017

While pulmonary mechanoreceptors appear to play little or no role in determining the eupneic breathing pattern in some species of vertebrates, they do in others as well as in all species under conditions of elevated respiratory drive. Tonic and phasic inputs from this receptor group have independent roles in determining breathing pattern. Thus withholding lung inflation produces very different results from receptor denervation. There are at least five phases to the respiratory cycle that appear to be under separate control. Tonic receptor input is involved primarily in regulating the length of the respiratory pause, which can occur at the end of inspiration or expiration, depending on the species. Phasic receptor input has different effects during different phases of the cycle as well as different effects at different times during a single phase. This activity contributes to phase switching during the ventilation cycle and thus to the regulation of breathing frequency and tidal volume. The significance of the modulatory effects of phasic input on the duration of different phases of the ventilation cycle is not totally clear, but the evidence suggests that phasic input acts to stabilize the respiratory pattern and may be instrumental in optimizing the breathing pattern in terms of ergometric costs. This appears to be the case in all vertebrate classes, despite dramatic differences in the mechanical events associated with ventilation arising from different respiratory pumps. These receptors also appear to have significant roles other than those associated with modulation of respiratory rhythm, particularly in lower vertebrates. Many of these roles, such as maintaining the integrity of the gill curtain in fish or buoyancy control and regulation of blood flow distribution in reptiles, may be as important as their role in modulating the endogenous rhythm.
Circadian rhythm in recognition threshold of salt taste in healthy subjects
Authors: Fujimura A. , Kajiyama H. , Tateishi T. , Ebihara A.
Published: December 2017

The circadian rhythm in recognition threshold of salt taste was examined in six healthy young subjects. Plasma aldosterone (PA) and cortisol concentrations, plasma renin activity (PRA), salivary sodium concentration, and salt recognition thresholds were measured every 3 h for a 24-h period. The salt recognition threshold and salivary sodium concentration exhibited similar circadian rhythms, with the lowest values recorded in the afternoon. Positive correlations were observed between the recognition threshold and salivary sodium (P less than 0.001) and between cortisol and PA (P less than 0.001). There was no correlation between PRA and PA. A negative correlation was observed between PA and salivary sodium concentration (P less than 0.01). These data indicate that the recognition threshold for salt taste has a circadian rhythm in young healthy subjects. This rhythm appears to be related to daily variations in the plasma aldosterone concentration and its subsequent effects on salivary sodium concentration.
Single-unit responses of serotonergic neurons to vasoactive drug administration in behaving cats
Authors: Fornal C. A. , Litto W. J. , Morilak D. A. , Jacobs B. L.
Published: December 2017

Single-unit activity of serotonergic neurons in the dorsal raphe nucleus (DRN), heart rate (HR), and arterial blood pressure were recorded in freely moving cats during spontaneous behavior and in response to systemic administration of vasoactive drugs. The activity of serotonergic neurons varied in association with behavioral arousal but was unrelated to spontaneous fluctuations in HR and blood pressure. Bolus administration of phenylephrine hydrochloride and sodium nitroprusside (15-20 micrograms/kg iv) produced a rapid transient increase (35 mmHg) and decrease (49 mmHg), respectively, in mean arterial pressure (MAP). Infusion of phenylephrine and sodium nitroprusside (100 micrograms/ml) produced sustained hypertension (avg MAP 166 mmHg) and hypotension (avg MAP 49 mmHg), respectively. The activity of serotonergic neurons was not significantly altered in response to phenylephrine or sodium nitroprusside administration. Furthermore, no significant changes in unit activity were observed after hydralazine administration (1 mg/kg iv) despite prolonged reflex activation of sympathetic outflow. Thus the activity of DRN serotonergic neurons was unrelated to transient alterations in blood pressure and baroreceptor activity. These results suggest that changes in the activity of serotonergic DRN neurons are not involved in physiological mechanisms underlying reflex alterations in sympathetic (and parasympathetic) outflow invoked by hypertension and hypotension.
Induction of plasma inhibitors of interleukin 1 and TNF-alpha activity by endotoxin administration to normal humans
Authors: Spinas G. A. , Bloesch D. , Kaufmann M. T. , Keller U. , Dayer J. M.
Published: December 2017

Several naturally occurring inhibitors of interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been demonstrated both in serum and urine of febrile patients. These factors are considered to be part of a regulatory system counteracting potential deleterious effects of the cytokines. We have assayed plasma samples of volunteers who received a bolus intravenous injection of either 4 ng/kg body wt of Escherichia coli endotoxin (n = 6) or 0.9% saline (n = 4) for the presence of IL-1 and TNF-alpha inhibitory activity. Plasma obtained 3 h after endotoxin injection inhibited IL-1-induced PGE2 release from fibroblasts by 57% (P less than 0.001 vs. baseline and saline controls, respectively). Maximal IL-1 inhibitory capacity coincided with fever and tended to disappear with declining body temperature. Normal plasma was found to inhibit TNF-alpha-induced PGE2 release by 20-35%. This inhibitory effect increased to 50-60% in plasma obtained during endotoxinemia. Maximal TNF-alpha inhibitory capacity became detectable when circulating TNF-alpha levels peaked at 120 min after the injection of endotoxin. Our data demonstrate that both IL-1 and TNF-alpha inhibitory activity can be induced experimentally by intravenous endotoxin administration to humans and that their appearance coincides with fever and circulating TNF-alpha levels.
Lysine transport by brush-border membrane vesicles of eel intestine: interaction with neutral amino acids
Authors: Vilella S. , Ahearn G. A. , Cassano G. , Maffia M. , Storelli C.
Published: December 2017

L-[3H]lysine uptake was measured in brush-border membrane vesicles prepared from intestinal mucosa of the European eel Anguilla anguilla. Lysine uptake occurred via 1) a nonsaturable component with an apparent diffusional permeability (P) of 0.58 microliter.mg protein-1.min-1,2) a Na-dependent transport system [half-saturation constant (Kapp) 0.16 mM, maximal transport rate (Jmax) 3.57 nmol.mg protein-1.min-1]; 3) a Na-independent transport system (Kapp 0.17 mM, Jmax 2.77 nmol.mg protein-1.min-1). Both carrier-mediated processes were accelerated by the presence of an intravesicular negative membrane potential. Hill analysis of L-lysine influx, over a wide range of external Na concentrations, resulted in a Hill coefficient (n) of approximately 2, suggesting that two or more Na ions may be associated with amino acid transport. The inhibition of lysine uptake by other amino acids was studied. Na-dependent lysine uptake was competitively inhibited by proline [inhibitory constant (Ki) approximately 2 mM] and may occur by a system specific for cationic amino acids. Na-independent lysine uptake was competitively inhibited by alanine (Ki approximately 1 mM) and may occur by a classic L system.
Temperature regulation of young coypus (Myocastor coypus) in air and water
Authors: Doncaster C. P. , Dumonteil E. , Barre H. , Jouventin P.
Published: December 2017

Coypus (Myocastor coypus Molina) have recently colonized temperate regions of Europe in large numbers, originating from populations indigenous to subtropical regions of South America. Observations of coypu behavior in the wild and in enclosures under a temperate climate showed a preference for close proximity to water and frequent swimming bouts. Little change was observed in the semiaquatic habit in winter, despite high mortality during this period, particularly among young and adult male coypus. Evidence for constraints on thermal adaptation was sought from measurements in a thermostatic chamber of the resting metabolic rate (RMR) of young coypus caught from wild populations in France and of the body (Tb) and skin (Tsk) temperatures as a function of ambient temperature (Ta). A light heterothermic response with deep Tb falling by 0.8 degree C and stabilizing at a new level of 36.7 degrees C was observed in water and air at Ta below the lower critical temperatures. In common with other semiaquatic mammals, RMR (2.94 W/kg) was high relative to terrestrial mammals of equivalent body mass. Minimal thermal conductance was 0.10 W.kg-1.degree C-1 in air for Ta between -10 and +20 degrees C, and conductance varied in water from 0.24 to 1.18 W.kg-1.degrees C-1 for Ta between 5 and 35 degrees C. The physiological adaptations to cold and particularly the high insulative value of the fur (80-90% of the insulation) help to explain the successful extension of the coypu's range to temperate regions. Energetic costs were nevertheless high in cold water, suggesting that social factors may be implicated in severe winter mortality, particularly dominance hierarchy regulating the persistent use of water bodies even under freezing conditions.
Thermal nociception potentiates the release of ACTH and norepinephrine by blood loss
Authors: Bereiter D. A. , Benetti A. P. , Thrivikraman K. V.
Published: December 2017

Neuroendocrine and autonomic responses were assessed in chloralose-anesthetized cats after nociceptor activation and after acute blood loss, two of the sensory components that accompany injury. Plasma adrenocorticotropic hormone (ACTH), catecholamines (peripheral and adrenal), and cardiovascular responses were examined after corneal thermal stimulation (52 degrees C), after hemorrhage (10 ml/kg), and after simultaneous presentation of these two stimuli. Corneal heat during hemorrhage evoked an exaggerated increase in plasma ACTH (+185 +/- 76 pg/ml, P less than 0.01) and in peripheral plasma norepinephrine (+0.41 +/- 0.11 ng/ml, P less than 0.01) compared with the responses seen after either stimulus alone. A peripheral origin of norepinephrine was indicated, since the adrenal secretion of catecholamines increased similarly after all stimuli. Extracellular levels of norepinephrine, collected by push-pull perfusion, within raphe pallidus increased after corneal heat but not after blood loss and did not reflect the interaction between these two stimuli. Results indicated that physiological stimulation of nociceptive and cardiovascular receptors interact to potentiate the release of ACTH and norepinephrine into peripheral blood, effects that were not predicted from the responses to either sensory input alone.
Sympatholytic response to stimulation of superior laryngeal nerve in rats
Authors: Huangfu D. H. , Guyenet P. G.
Published: December 2017

The central pathway mediating a sympatholytic response to stimulation of the superior laryngeal nerve (SLN) was studied in halothane-anesthetized, paralyzed rats. Single-pulse stimulation of SLN inhibited lumbar sympathetic nerve discharge (LSND) with onset latency of 113 +/- 1.7 ms. LSND inhibition was markedly attenuated by bilateral microinjection of kynurenic acid (Kyn, glutamate receptor antagonist, 4.5 nmol/side) into the caudal ventrolateral medulla (CVL) or by bilateral administration of bicuculline methiodide (Bic; gamma-aminobutyric acid-receptor antagonist, 225 pmol/side) into the rostral ventrolateral medulla (RVL). In 13 of 14 cases, the baroreceptor reflex was also severely reduced. Injections of Bic or Kyn elsewhere in the medullary reticular formation were ineffective. Single-pulse stimulation of SLN inhibited 19 of 26 RVL reticulospinal barosensitive cells (onset latency 46 +/- 1.4 ms). This inhibition was attenuated (from 92 +/- 6 to 14 +/- 12%) by iontophoretic application of Bic (n = 7), which also reduced the cells' inhibitory response to aortic coarctation. The remaining seven barosensitive neurons were unaffected by SLN stimulation. In conclusion, the sympathetic baroreflex and the sympathoinhibitory response to SLN stimulation appear to be mediated by similar medullary pathways.
Axial diffusion and Michaelis-Menten kinetics in oxygen delivery in rat peripheral nerve
Authors: Lagerlund T. D. , Low P. A.
Published: December 2017

Our simulation of the release, diffusion, and consumption of oxygen in the capillaries and surrounding tissue of peripheral nerve now includes axial diffusion in blood and in surrounding tissue, in addition to bulk flow of blood and radial diffusion of oxygen out of the capillary. Our simulation assumes that the oxygen consumption of nerve tissue obeys Michaelis-Menten kinetics rather than zero-order kinetics as had been assumed in the Krogh model. We can calculate the oxygen tension at all points in the capillary and surrounding tissue as a function of distance from the center of the nearest capillary and distance along the capillary from the arterial to the venous end. Using average measured values for microcirculatory parameters in rat nerve, we calculated a distribution of oxygen tension values that agrees with experimentally measured distributions. The effects of axial diffusion and of Michaelis-Menten kinetics on the oxygen distributions were noticeable under normal conditions, but these effects were much more important in situations in which oxygen delivery was adversely affected.
Dynamics of interstitial and intracellular pH in evolving brain infarct
Authors: Nedergaard M. , Kraig R. P. , Tanabe J. , Pulsinelli W. A.
Published: December 2017

We examined the relationships between intracellular pH (pHi) and interstitial pH (pHe) in a rat model of focal ischemia. Interstitial pH was measured with pH-sensitive microelectrodes, and the average tissue pH was measured with the [14C]dimethadione method in rats subjected to occlusion of the right middle cerebral and common carotid arteries (MCA-CCAO). In normal cortex, pHe and pHi were 7.24 +/- 0.97 and 7.01 +/- 0.13 (means +/- SD, n = 6), respectively. In the ischemic cortex, pHe fell to 6.43 +/- 0.13, whereas pHi decreased only to 6.86 +/- 0.11 (n = 5) 1 h after MCA-CCAO. After 4 h of ischemia, the pHe was 6.61 +/- 0.09 and pHi was 6.62 +/- 0.20 (n = 4). Treatment with glucose before ischemia markedly lowered the pHe (5.88 +/- 0.17) but not pHi (6.83 +/- 0.03, n = 4) measured 1 h after ischemia. In the ischemic cortex of animals made hypoglycemic by pretreatment with insulin, neither pHe (7.25 +/- 0.06) nor pHi (6.99 +/- 0.13, n = 4) decreased. The demonstrated difference in pHi and pHe indicates that some cells remained sufficiently functional to maintain a plasma membrane gradient of protons within the evolving infarct. If the calculated pHi values accurately reflect the true pHi of cells within zones of severe focal ischemia, then cerebral infarction can proceed at pHi levels not greatly altered from normal.
Half-life, hemodynamic, renal, and hormonal effects of prorenin in cynomolgus monkeys
Authors: Lenz T. , Sealey J. E. , Maack T. , James G. D. , Heinrikson R. L. , Marion D. , Laragh J. H.
Published: December 2017

Prorenin is found in human plasma, kidneys, and reproductive organs. We investigated the physiological and pharmacokinetic properties of plasma prorenin, and its plasma conversion to active renin, by bolus infusions of human recombinant prorenin (0.5, 2, 20 micrograms; n = 4/dose) into anesthetized male cynomolgus monkeys. The infused prorenin had 3% intrinsic renin activity. Plasma prorenin rose from 61 +/- 6 to 101 +/- 11, 570 +/- 46, and 7,700 +/- 390 ng.ml-1.h-1, respectively, after 5 min. Plasma renin increased to 3% of total renin, angiotensin II increased less than twofold, and aldosterone did not change. Plasma testosterone fell slightly (P less than 0.01). Mean arterial pressure (MAP) fell slowly from 104 +/- 3 to 93 +/- 3 mmHg at 60 min (P less than 0.001). Heart rate, glomerular filtration rate, renal plasma flow, and urinary sodium and potassium excretion were unchanged. For the 2- and 20-micrograms doses, respectively, effective half-life of plasma decay was 47 +/- 4.9 and 109 +/- 21 min (P less than 0.05), apparent volume of distribution was 145 +/- 11 and 166 +/- 35 ml/kg, and metabolic clearance rate was 2.30 +/- 0.44 and 1.08 +/- 0.14 ml.min-1.kg-1 (P less than 0.01). In conclusion, neither the hormonal nor the physiological response to infusion of pharmacologic levels of recombinant human prorenin into monkeys provide evidence for conversion of circulating prorenin to renin. MAP did not increase and actually fell without commensurate effects on renal function. The half-life of recombinant prorenin was similar to that of renin.
Failure of acute saralasin to reverse chronic hypertension in fetal lambs
Authors: Anderson D. F. , Binder N. D.
Published: December 2017

Upper body arterial hypertension developed in 12 fetal lambs after chronic suprarenal aortic blood flow reduction. Sixty minutes after blood flow reduction, intravenous saralasin infusion was able to reduce upper body mean arterial blood pressure to control levels. Although saralasin infusion was able to decrease upper body arterial blood pressure after 1 day of hypertension, it was not able to return blood pressure to control levels. Three or more days later, saralasin was unable to cause a significant reduction in upper body arterial blood pressure. We conclude that, although the renin-angiotensin system has a role in maintaining the elevated blood pressure after greater than or equal to 1 day of suprarenal aortic blood flow reduction, some other mechanism also participates. We have ruled out a role for changing blood volume, and our results suggest that an elevation of plasma catecholamines is not responsible. Some other pathway for fluid regulation available to the fetus may be responsible.
Alcohol-induced downregulation of superoxide anion release by hepatic phagocytes in endotoxemic rats
Authors: Bautista A. P. , D'Souza N. B. , Lang C. H. , Bagwell J. , Spitzer J. J.
Published: December 2017

Bacterial endotoxins [lipopolysaccharide (LPS)] are potent immunomodulators, and ethanol is known to depress certain immune defense mechanisms. Thus the combined impact of these two agents on the generation of superoxide anion (O2(-).) by isolated hepatic phagocytic cells was investigated. Ethanol was infused intravenously into rats for 7 h, and Escherichia coli LPS was injected intravenously at 4 h after ethanol administration. Control groups received an equal volume of saline or ethanol alone. Nonparenchymal cells that were composed of endothelial and Kupffer cells and few polymorphonuclear neutrophils (PMN; less than 1%) were obtained after collagenase-pronase digestion. In the LPS-treated rats, the total number of PMN per liver increased significantly. Histological sections of the liver showed PMN infiltration and areas of necrosis after LPS treatment with or without ethanol. In the presence of either phorbol 12-myristate 13-acetate or opsonized zymosan in vitro, Kupffer cells and hepatic PMN from LPS-treated rats generated large amounts of O2(-).. Ethanol intoxication in vitro by these cells to 50%. Ethanol alone (without LPS) had no effect on the production of O2(-).. These studies demonstrate that ethanol intoxication was associated with the downregulation of the LPS-enhanced in vivo priming of hepatic phagocytes to generate O2(-). in vitro and may thus contribute to the enhanced susceptibility of alcoholic subjects to develop an infection.
31P-NMR study of normoxic and anoxic perfused turtle heart during graded CO2 and lactic acidosis
Authors: Jackson D. C. , Arendt E. A. , Inman K. C. , Lawler R. G. , Panol G. , Wasser J. S.
Published: December 2017

We studied the effects of graded acidosis (both CO2 and lactic acid) and anoxia on intracellular pH (pHi) regulation, high-energy phosphates, and mechanical function of isolated perfused hearts of the turtle (Chrysemys picta bellii) at 20 degrees C using 31P-nuclear magnetic resonance (NMR) spectroscopy. During CO2 acidosis, anoxia had no effect on apparent nonbicarbonate buffer value (d[HCO3-]/dpHi = 71 and 89 mM/pH in normoxia and anoxia, respectively) or on pHi regulation (dpHi/dpHe = 0.52 and 0.43 in normoxia and anoxia, respectively, where pHe is extracellular pH). During normoxic lactic acidosis, dpHi/dpHe was similar to the values observed in CO2 acidosis and averaged 0.55 overall. During anoxic lactic acidosis, however, similar regulation occurred over only a narrow range of pHe, and then dpHi/dpHe increased to greater than 1.0 at pHe less than 7.1. Creatine phosphate (CP), calculated as the area of the NMR peak, fell more in response to normoxic CO2 acidosis than to normoxic lactic acidosis; in anoxia, the fall in CP was further increased but to similar extreme levels (10-20% of control) in both acid perfusions. Cardiac output and maximum rate of pressure development each fell during acidosis in similar fashion in all protocols, and the responses were similar in normoxic and anoxic hearts. Heart rate, in contrast, decreased during acidosis, but this effect was more pronounced when hearts were anoxic. We conclude that the effect of acidosis on cardiac function can depend on the type of acidosis imposed. Based on the heart's insensitivity to anoxia alone, we suggest that anoxia may normally depress function indirectly via its effect on intracellular acid-base state.