Biomedical subjects

D B Jennings

Publications and source records attributed to D B Jennings.

At least 19 recordsLinked to original sources

PubMed2001

Respiratory and metabolic effects of decreased osmolality in conscious rats.

We investigated the respiratory and metabolic effects of decreased osmolality, and the potential roles of angiotensin II (ANG II) and the subfornical organ (SFO) in mediating these effects, in conscious Sprague-Dawley (SD) rats. Gastric water loading was induced either by oral gavage or an externalized indwelling stomach tube (20 mL x kg(-1) distilled water at body temperature). Repeated measurements after oral gavage were obtained with and without water loading and with and without ANG II receptor block (saralasin, 1.3 microg x kg(-1) x min(-1) iv). At 15 min after water loading by oral gavage, ventilation (V, 1.14+/-0.08 L x kg(-1) x min(-1)) and tidal volume (10.7+/-0.6 mL x kg(-1)) were transiently higher (P < 0.05), at a time when plasma osmolality was decreased (-8+/-1 mOsm), compared with gavage tube alone (0.95+/-0.08 L x kg(-1) min(-1) and 9.1+/-0.7 mL x kg(-1), respectively). However, water loading via stomach tube did not stimulate V; only during the 60-s period of water infusion did V increase briefly, but this was due to increased respiratory frequency. Dye indicators demonstrated that oral gavage exposes upper airway and esophageal afferents to water, presumably accounting for respiratory stimulation. Lesions of the SFO did not affect respiration or metabolism. A decrease in osmolality, associated with both water loading techniques, caused a sustained increase in oxygen consumption (Vo2 ) and a decrease in the V/Vo2 ratio. ANG II receptor block reduced the Vo2 response and prevented the decrease in V/Vo2 following water loading by oral gavage, but did not affect the transient stimulation of V. Unlike larger mammals, decreased osmolality does not stimulate respiration in the SD rat.

Angiotensin Receptor Antagonists↗

PubMed2001

Cardiorespiratory effects of prolonged angiotensin II block in resting conscious dogs.

Intravenous (iv) infusion of the angiotensin II (ANG II) receptor blocker saralasin in resting conscious dogs during physiological pertubations, such as hypotension and prolonged hypoxia, indicates the presence of an ANG II drive to increase respiration and decrease the arterial partial pressure of CO2 (PaCO2). In contrast, in eupneic resting dogs on a regular chow diet, iv infusion of saralasin for short periods (up to 30 min) provides no evidence of a tonic effect of circulating levels of ANG II on acid-base balance, respiration, metabolism, or circulation. However, ANG II influences physiological processes involving salt, water, and acid-base balances, which are potentially expressed beyond a 30 min time period, and could secondarily affect respiration. Therefore, we tested the hypothesis that blocking ANG II with iv saralasin would affect respiration and circulation over a 4-h period. Contrary to the hypothesis, iv infusion of saralasin in resting conscious eupneic dogs on a regular chow diet over a 4-h period had no effects on plasma strong ions, osmolality, acid-base balance, respiration, metabolism, or circulation when compared with similar control studies in the same animals. Thus, ANG II does not play a tonic modulatory role in respiratory control under "normal" physiological conditions.

Acid-Base Equilibrium↗

PubMed2000

Angiotensin stimulates respiration in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) have an activated brain angiotensin system. We hypothesized 1) that ventilation (V) would be greater in conscious SHR than in control Wistar-Kyoto (WKY) rats and 2) that intravenous infusion of the ANG II-receptor blocker saralasin would depress respiration in SHR, but not in WKY. Respiration and oxygen consumption (VO(2)) were measured in conscious aged-matched groups (n = 16) of adult female SHR and WKY. For protocol 1, rats were habituated to a plethysmograph and measurements obtained over 60-75 min. After installation of chronic intravenous catheters, protocol 2 consisted of 30 min of saline infusion ( approximately 14 microliter. kg(-1). min(-1)) followed by 40 min of saralasin (1.3 microgram. kg(-1). min(-1)). V, tidal volume (VT), inspiratory flow [VT/inspiratory time (TI)], breath expiratory time, and VO(2) were higher, and breath TI was lower in "continuously quiet" SHR. In SHR, but not in WKY rats, ANG II-receptor block decreased V, VT, and VT/TI and increased breath TI. During ANG II-receptor block, an average decrease in VO(2) in SHR was not significant. About one-half of the higher V in SHR appears to be accounted for by an ANG II mechanism acting either via peripheral arterial receptors or circumventricular organs.

Angiotensin II↗

PubMed1998

Roles for mannitol and mannitol dehydrogenase in active oxygen-mediated plant defense.

Reactive oxygen species (ROS) are both signal molecules and direct participants in plant defense against pathogens. Many fungi synthesize mannitol, a potent quencher of ROS, and there is growing evidence that at least some phytopathogenic fungi use mannitol to suppress ROS-mediated plant defenses. Here we show induction of mannitol production and secretion in the phytopathogenic fungus Alternaria alternata in the presence of host-plant extracts. Conversely, we show that the catabolic enzyme mannitol dehydrogenase is induced in a non-mannitol-producing plant in response to both fungal infection and specific inducers of plant defense responses. This provides a mechanism whereby the plant can counteract fungal suppression of ROS-mediated defenses by catabolizing mannitol of fungal origin.

Journal Article↗

PubMed1998

Ventilatory and metabolic effects of hypercapnia in conscious rats: AVP V1 receptor block.

In conscious dogs, arginine vasopressin (AVP) inhibits an angiotensin II drive to ventilation during air breathing and during acute hypercapnia. To determine whether AVP inhibits respiration in rats, as in dogs, respiration and metabolism were measured in six male Sprague-Dawley rats using a plethysmograph. Rats breathed air, followed by 5% and 6.5% CO2 with or without AVP V1 receptor block. In unblocked experiments, minute ventilation (V) increased to a comparable level during inhalation of both CO2 gas mixtures, resulting in a flattening of the ventilatory response to increased Paco2. However, oxygen consumption decreased during 6.5% CO2, compared with 5% CO2, so that the ventilatory equivalent for O2 increased in a more linear manner with respect to Paco2. The main effect of AVP V1 receptor block was to increase mean arterial blood pressure; there was no significant effect of AVP V1 receptor block on respiratory responses. AVP does not inhibit respiration in conscious rats as it does in conscious dogs.

Animals↗

PubMed1998

Angiotensin II modulates respiratory and acid-base responses to prolonged hypoxia in conscious dogs.

We tested the hypothesis that angiotensin II (ANG II) contributes to ventilatory and acid-base adaptations during 3-4 h of hypoxia (partial pressure of O2 in arterial blood approximately 43 Torr) in the conscious dog. Three protocols were carried out over 3-4 h in five dogs: 1) air control, 2) 12% O2 breathing, and 3) 12% O2 breathing with ANG II receptors blocked by infusion of saralasin (0. 5 microg . kg-1 . min-1). After 2 h of hypoxia, expired ventilation and alveolar ventilation progressively increased, and the partial pressure of CO2 in arterial blood and the difference between the arterial concentrations of strong cations and strong anions ([SID]) decreased. When the hypoxic chemoreceptor drive to breathe was abolished transiently for 30 s with 100% O2, the resultant central apneic time decreased between 0.5 and 2.5 h of hypoxia. All these adaptive responses to hypoxia were abolished by ANG II receptor block. Because plasma ANG II levels were lower during hypoxia and hypoxic release of arginine vasopressin from the pituitary into the plasma was prevented by ANG II receptor block, the brain renin-angiotensin system was likely involved. It is possible that ANG II mediates ventilatory and acid-base adaptive responses to prolonged hypoxia via alterations in ion transport to decrease [SID] in brain extracellular fluid rather than acting by a direct neural mechanism.

Acclimatization↗

PubMed1997

Breath timing, volume and drive to breathe in conscious rats: comparative aspects.

In conscious animals, respiratory frequency (f) and tidal volume (VT) vary breath to breath. Examining the average value of variables associated with specific bins of another variable, such as breath f, provides a unique tool to examine respiratory behaviour. In conscious Sprague-Dawley rats respiratory breath timing, tidal volume (VT) and drive (VT/TI) were characterized using a plethysmograph. In the majority of rats at low breath f, expiratory time (TE) exceeded inspiratory time (TI) and these times became equal as f exceeded 150 breaths/min; there was no evidence for TI greater than TE at higher f, as observed in cats and dogs. When VT is normalized per kg, rat breath VT and VT/TI, binned by breath f, are continuous with those for the cat and non-panting dog at the lowest breath f. Relative to breath f, breath VT and VT/TI in rats are greater than in normothermic panting dogs (20 degrees C), but only slightly greater than those variables in panting dogs in the heat (30 degrees C). Lower values of breath VT/TI, binned by breath f or V, in cats and dogs are compensated for by a greater TI relative to the duration of a given breath. This comparative analysis suggests continuities of respiratory pattern generation among species.

Animals↗

PubMed1996

Isozyme Variation among Biological Species in the Gibberella fujikuroi Species Complex (Fusarium Section Liseola).

Isozyme phenotypes were determined for 101 strains of Gibberella fujikuroi and 2 strains of Gibberella nygamai that represent seven biological species (mating populations) isolated from a variety of plant hosts in dispersed geographic locations. Fourteen enzymes were resolved in one or more of three buffer systems. Two of the enzymes, arylesterase and acid phosphatase, were polymorphic within two or more biological species and are suitable for intraspecific studies of population variation. Six enzymes, alcohol dehydrogenase, aspartate aminotransferase, glucose-6-phosphate dehydrogenase, mannitol dehydrogenase, phosphoglucomutase, and phosphogluconate dehydrogenase, were monomorphic in all of the isolates examined. The remaining six enzymes, fumarase, glucose phosphate isomerase, glutamate dehydrogenase (NADP), isocitrate dehydrogenase (NADP), malate dehydrogenase, and triose-phosphate isomerase, could potentially be used to distinguish the different biological species. Mating populations C and D are the most similar, since the mating population C isolates examined had the same isozyme phenotype as did a subset of the isolates in mating population D. Mating population E is the least similar to the other taxa examined. Unique isozyme phenotypes are present but are composed of banding patterns shared among the biological species. This finding supports the hypothesis that these biological species, with the possible exception of mating populations C and D, are reproductively isolated from one another and that no significant gene flow is occurring between them. Isozyme analysis is a useful method to distinguish these closely related biological species. Examination of isozyme phenotypes is more rapid than the present technique, which is based on sexual crosses; can be applied to strains that are not sexually fertile; and is more sensitive than traditional morphological characters, which cannot distinguish more than three or four morphological groups among the seven biological species. While emphasizing the discreteness of the mating populations as biological entities, our isozyme data also reaffirm the close genetic relationship among these groups.

Journal Article↗

PubMed1996

Respiration during acute hypoxia: angiotensin- and vasopressin-receptor blocks.

In normoxic conscious dogs, increased angiotensin II (ANG II), or activation (disinhibition) of the renin-angiotensin system by vasopressin (AVP) V1-receptor block, increases ventilation and decreases arterial PCO2. Both hormones can be increased during hypoxia and might modulate ventilatory drive. Six conscious dogs were studied before and during hypocapnic, isocapnic, and hypercapnic hypoxia. To study potential hormonal effects during hypocapnic hypoxia, experiment 1 included three protocols in which 12.8% O2 was breathed for 60 min: protocol 1, control studies without block; protocol 2, AVP V1 receptors were blocked at the onset of hypoxia; and protocol 3, ANG II receptors were blocked 20 min before hypoxia. To study potential effects of acid-base changes during acute hypoxia, experiment 2 included two protocols (with and without AVP V1-receptor block). A 40-min period of hypocapnic hypoxia was followed by two successive 20-min periods with hypoxia maintained but inspired CO2 progressively increased. Neither hormonal block affected respiration during the hypoxic conditions. Unlike normoxia in conscious dogs, during acute hypoxia, respiratory control by ANG II is not modulated by AVP and acid-base effects on receptors do not account for this difference.

Acid-Base Equilibrium↗

PubMed1996

Ventilatory effects of angiotensin and vasopressin in conscious rats.

Angiotensin II (ANG II) stimulates ventilation (V), when ventilatory baroreceptor reflexes are taken into account, and arginine vasopressin (AVP) causes baroreflex inhibition of V in conscious and anesthetized dogs. To study mechanisms of hormonal modulation of V, a conscious rat model was investigated. V and metabolism were measured during steady-state intravenous infusions of ANG II and AVP in Sprague-Dawley rats (mean arterial pressure (MAP) increased 20 mmHg (1 mmHg = 133.3 Pa)). These data were compared with observations during equal pressor infusions of phenylephrine (PE), an agent classically used to study baroreceptor reflexes. V, respiratory frequency (f), and tidal volume (Vt) were maintained during the increased MAP associated with ANG II infusions, a response identical with that reported in conscious dogs. However, unlike dogs, AVP infusion did not depress V and metabolism in rats. PE in conscious rats caused an unexpected increase in Vt and V in association with increased metabolism. None of the pressor agents affected breath timing when the latter was binned by breath f. Since there was no obvious baroreflex inhibition of V with AVP and PE, potential stimulatory effects of ANG II on respiration could not be discerned. As well, the ventilatory baroreceptor pressure threshold may be higher or adaptation of the reflex may be faster in conscious rats than in dogs.

Angiotensin II↗

PubMed1995

The antidiuretic effect of pneumadin requires a functional arginine vasopressin system.

Pneumadin is an antidiuretic decapeptide, recently isolated from rat and human lung. Bolus intravenous injection of 5 nmol of pneumadin into water-loaded rats caused a rapid and significant antidiuresis and a reduction in Na+ and Cl- excretion. Pneumadin administration did not alter mean arterial pressure, right atrial pressure, heart rate or haematocrit. Bolus intravenous injection of 20 nmol of pneumadin into non-water-loaded rats caused a significant increase in arginine vasopressin (AVP) within 10 min. Pneumadin administration also increased circulating atrial natriuretic peptide (ANP) but did not alter aldosterone or plasma renin activity levels. Injection of pneumadin into water-loaded Brattleboro rats, which genetically lack circulating AVP, did not change urine flow, confirming that the pneumadin induced antidiuresis is AVP dependent. Radioactive pneumadin was cleared from the circulation with a t1/2 beta of 480.3 s. Radioactive pneumadin, isolated from plasma, eluted at an altered position on reverse phase HPLC, which indicated that the peptide was modified in vivo. This modification was also observed when synthetic pneumadin was incubated in rat plasma in vitro. Purification and sequencing of the modified synthetic peptide indicated that the modification is not a proteolytic cleavage. These results indicate that pneumadin injected into the rat caused an antidiuresis by altering circulating AVP levels.

Aldosterone↗

PubMed1995

During acute hypercapnia vasopressin inhibits an angiotensin drive to ventilation in conscious dogs.

Intravenous infusion of arginine vasopressin (AVP) depresses the slope of the ventilatory response to CO2 during acute hypercapnia. We therefore tested the hypothesis that AVP V1-receptor blockade would increase the slope of the ventilatory response to CO2. After a 20-min control period, an AVP V1-receptor antagonist (d(CH2)5[Tyr(Me)2]AVP) was injected into six conscious resting dogs. Thirty minutes after AVP V1-receptor blockade, dogs were exposed to sequential 20-min periods of 5 and 6.5% inspired CO2 in air. A second protocol (no AVP V1-receptor blockade) was conducted as a control. As predicted, AVP V1-receptor blockade enhanced ventilation during inhalation of 6.5% CO2 in association with an increased metabolic rate and increased plasma angiotensin II (ANG II). In eupneic dogs, stimulation of respiration by AVP V1-receptor blockade is mediated by ANG II. A third protocol with ANG II-receptor blockade (intravenous infusion of saralasin) combined with AVP V1-receptor blockade indicated that ANG II mediated the increase in metabolism and the augmented ventilation during inhalation of 6.5% CO2. We conclude that during acute hypercapnia of sufficient magnitude, and perhaps duration, AVP inhibits an ANG II-mediated stimulation of metabolism and respiration.

Acid-Base Equilibrium↗

PubMed1994

Respiratory control during exercise: hormones, osmolality, strong ions, and PaCO2.

For optimal performance of exercising muscle, the charge state of proteins must be maintained; the pH environment of protein histidine imidazole groups must be coordinated with their pK. During exercise, increasing temperature and osmolality as well as changes in strong ions affect the pK of imidazole groups. Production of strong organic anions also decreases the concentration difference between strong cations and anions (strong ion difference, or [SID]), causing a metabolic acidosis in peripheral tissues. Central chemoreceptors regulate PCO2 in relation to the [SID] of brain fluids to maintain a "constant" brain [H+]. In addition, increased osmolality, angiotensin II, and vasopressin during exercise may stimulate circumventricular organs of the brain and interact with chemical control of ventilation. Changes in [SID] of brain fluids during exercise are negligible compared to systemic decreases in [SID]; thus, regulation of PCO2 to maintain brain [H+] homeostasis cannot simultaneously compensate for greater changes in [SID] in peripheral tissues.

Acid-Base Equilibrium↗

PubMed1994

The physicochemistry of [H+] and respiratory control: roles of PCO2, strong ions, and their hormonal regulators.

I describe how the dietary intake of strong ions potentially affects the regulation of ventilation and the PCO2 of body fluids in two ways. First, changing the dietary intake of NaCl can alter the concentration difference between strong cations and strong anions (the [SID] of Stewart) of body fluids. Experimental observations indicate that the [SID] in brain fluids or cerebrospinal fluid ([SID]CSF) could be the stimulus to central chemoreceptors. [SID]CSF consistently predicts ventilatory regulation of PCO2, whereas [H+]CSF does not. PCO2 acts as a stimulus to ventilation independently of [SID]CSF and possibly at higher as well as lower centers of the nervous system. I relate the concept of [SID] regulation of arterial PCO2 to the alphastat hypothesis of protein function, respiratory control, and [H+] homeostasis. Second, altering the dietary intake of NaCl changes the levels of hormones involved in salt and water balance. Angiotensin II acts centrally to stimulate ventilation. Evidence for the roles of both the renal and brain renin-angiotensin systems in respiratory control, and the modulation of respiratory control by vasopressin are reviewed. These peptide systems probably act via circumventricular organs of the brain to affect respiratory control and (or) by changing strong ion concentrations in brain fluids. Questions to be resolved on the role of [SID]CSF and hormones in respiratory adaptations, and experiments required to improve our understanding of the control of ventilation, are addressed in the concluding comments.

Acid-Base Equilibrium↗

PubMed1994

Effects of hypercapnia on metabolism, temperature, and ventilation during heat and fever.

We wished to determine whether 1) acute hypercapnia in cats changes metabolic heat production to affect temperature regulation and 2) heat exposure and fever affect the normal response. The effects of breathing 4% CO2 on O2 consumption (VO2), rectal temperature (Tre), and ventilation (V) were measured in five conscious resting cats. Cats were exposed to a normal (24-27 degrees C) chamber temperature (Ta) and a warm (33-34 degrees C) chamber Ta. Fever was produced by intravenous injection of Escherichia coli endotoxin (0.02 microgram/kg) at a normal Ta. In normothermic cats, hypercapnia decreased VO2 by approximately 40%, despite an increased V (approximately 100%), but Tre decreased only transiently and slightly compared with studies in which air was breathed throughout. During heat studies, average V was elevated but VO2 was markedly lower than at the normal Ta; Tre gradually increased. Hypercapnia combined with heat did not cause additional increases in VO2, nor did it cause a decrease in VO2, as at a normal Ta; however, the rate of rise of Tre during heat was slowed by hypercapnia. During febrigenesis, hypercapnia prevented the transient increase in VO2 observed when air was breathed and delayed the rate of rise in Tre. As Tre was falling in fever, hypercapnia depressed VO2 but did not affect Tre compared with fever studies in which air was breathed. Unlike heat exposure, hypercapnia had a further additive stimulatory effect on the increase in V at the onset of fever, and it increased V during the falling phase of fever when V had returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Angiotensin mediates stimulation of ventilation after vasopressin V1 receptor blockade.

We tested the hypothesis that respiration would be stimulated after vasopressin (AVP) V1 receptor blockade because of disinhibition and activation of the renin-angiotensin system. Intravenous infusion of angiotensin II (ANG II) stimulates respiration, presumably centrally, via circumventricular organs. In the present study, the AVP V1 receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine]-Arg8-AVP (PMP; 10 micrograms/kg i.v.) was administered to six awake resting dogs. Measurements were made 30 min prior, and 60 min subsequent, to injection of PMP (protocol 1). In three other protocols, the ANG II blocker saralasin (0.5 microgram.kg-1.min-1 i.v.) was infused starting 20 min before PMP (protocol 2) and 30 min after PMP (protocol 4) and saline was infused (0.2 ml/min) over 90 min as a control (protocol 3). After PMP in protocol 1, alveolar ventilation increased and arterial PCO2 decreased (approximately 3 Torr). ANG II receptor blockade prevented (protocol 2) and reversed (protocol 4) respiratory stimulation by PMP. Despite ventilatory stimulation, plasma renin activity and ANG II were not increased after PMP relative to control (protocol 3). We conclude that AVP acts at V1 receptors to inhibit formation of brain ANG II. Brain ANG II must modulate respiratory control via a circumventricular organ, because systemically administered saralasin, which does not cross the blood-brain barrier, blocked stimulation of respiration.

Amino Acid Sequence↗

PubMed1993

Circulatory and metabolic responses in awake dogs to infusion of iso-rANP/(rBNP).

We reported that a second rat atrial peptide, iso-atrial natriuretic peptide (iso-rANP(1-45)) and a potential putative homologue, iso-rANP(17-45) (identical with rat brain natriuretic peptide except for one amino acid) elicited circulatory and renal responses in anesthetized rats. In the present studies, low-dose intravenous infusions of iso-rANP(1-45) (6.3-25 pmol kg-1 min-1) and iso-rANP(17-45) (12.5-50 pmol kg-1 min-1) into conscious dogs produced subtle circulatory effects compared to control studies. Relative to oxygen consumption, cardiac output was lower and total peripheral resistance higher with both iso-rANP(1-45) and iso-rANP(17-45). Heart rate tended to be slightly lower relative to control studies during peptide infusions, and the highest infusion doses caused a decrease in mean arterial pressure. Plasma protein increased and plasma osmolality decreased with iso-rANP(1-45); infusion of iso-rANP(17-45) caused a decrease in the respiratory exchange ratio. The mechanism of action of iso-rANP may have been direct, via an active receptor. However, we previously reported for these same experiments that infusion of iso-rANP(1-45) and iso-rANP(17-45) increased plasma ANP and decreased plasma renin activity. Thus, circulatory changes during infusion of iso-rANP were consistent with an indirect mechanism related to increased endogenous ANP.

Acid-Base Equilibrium↗

PubMed1993

Breathing for protein function and [H+] homeostasis.

Based on a physicochemical analysis of H+ homeostasis, we hypothesize that PCO2 and strong ions, and not [H+], act independently on chemosensors in the central nervous system to regulate ventilation. [H+] in body fluids and the pK of histidine imidazole groups of proteins must be regulated in relation to each other to preserve protein conformation and function. Three independent variables regulate [H+] in body fluids: P(CO2), the strong ion difference ([SID]; ([Na+] + [K+]) - ([Cl-] + [lactate-])), and total weak anion. Temperature, osmolality and strong ions affect the pK of proteins. Our data and the literature support the hypothesis that [SID] is the stimulus to central medullary chemoreceptors and ventilation. The resulting change in PCO2 counterbalances change in [SID] and maintains [H+] constant. For example, a diet low in NaCl predisposes to a high [SID] (acts to decrease [H+]); increased [SID] increases the PaCO2 threshold of the ventilatory response to CO2, decreases alveolar ventilation, and increases PCO2 to maintain [H+] 'constant'. Because ventilation is stimulated by changes in PCO2 at constant [SID], PCO2 acts independently of [SID]. As well, change in osmolality and/or angiotensin II level, associated with alterations in water and electrolyte balance, act as stimuli to ventilation and interact with chemical control. Establishing the contributions of these neural, humoral and chemical mechanisms in respiratory adaptations will provide a challenge for future investigation.

Acid-Base Equilibrium↗