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G M Malvin

Publications and source records attributed to G M Malvin.

At least 19 recordsLinked to original sources
PubMed2001

Sites and ionic mechanisms of hypoxic vasoconstriction in frog skin.

We tested the hypothesis that the cellular mechanisms mediating hypoxic vasoconstriction (HVC) in frog skin, an important vertebrate respiratory organ, are similar to those mediating HVC in the pulmonary vasculature of mammals. An accepted hypothesis in the lung is that alveolar hypoxia alters the redox potential in vascular smooth muscle cells of arterial vessels. This decreases membrane K+ conductance, causing depolarization. Depolarization increases the open probability of L-type Ca2+ channels, facilitating Ca2+ entry into the cell, which leads to vascular smooth muscle contraction and vasoconstriction. We studied the cutaneous microcirculation of the frog (Xenopus laevis) web by enclosing the web in a transparent chamber that was ventilated with different gas mixtures. Arteriolar and venular diameters were measured by video microscopy. Drugs were applied topically or intravascularly. A dose-dependent constriction to hypoxia occurred in arterioles but not venules, although both vessel types constricted to similar degrees to the thromboxane mimetic U-46619. The magnitude of HVC was not associated with arteriolar size. Constriction of arterioles with 4-amino pyridine, a K+-channel antagonist, was blocked by the L-type Ca2+-channel blocker nifedipine. Nifedipine also antagonized HVC and hypercapnic vasoconstriction. Bay K 8664, a drug that increases the open probability of L-type Ca2+ channels, augmented HVC. These data support our hypothesis that the cellular mechanisms mediating HVC are similar in frog skin and mammalian lungs. This similarity between amphibian and mammalian tissues suggests that the mechanisms of HVC may have arisen relatively early in vertebrate evolution. In addition, because of its structural simplicity and easy accessibility, frog skin may be a useful tissue for studying this general phenomenon in vivo.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Thermoregulatory changes by hypoxia: lessons from the paramecium.

1. In organisms ranging from paramecia to mammals, hypoxia elicits a regulated decrease in body temperature (Tb). A decrease in Tb is an important adaptation to hypoxia primarily because it lowers metabolic rate when oxygen supply is limited, thus facilitating survival. 2. Although this beneficial response is extremely widespread among taxa, little is known of the cellular mechanisms that mediate hypoxia-induced decreases in Tb. This is due, in large part, to the extreme complexity of vertebrate thermoregulatory systems. 3. The thermoregulatory system of the unicellular paramecium is much simpler than that of vertebrates, yet it responds similarly to hypoxia. Research has explored the functional importance of hypoxia-induced decreases in Tb. In addition, a number of possible mediators and signalling pathways in hypoxia-induced reductions in Tb have been assessed. 4. In Paramecium caudatum, hypoxia appears to exert its thermoregulatory effects by inhibiting oxidative phosphorylation. Decreases in intracellular [ATP] and pH may be important intermediate signals. In addition, an endogenous opioid system appears to help mediate hypoxia-induced changes in thermoregulatory behaviour.

Animals↗
PubMed1996

Hypoxia decreases opioid delta receptor expression in mouse brain.

Delta opioid receptor activation is protective during hypoxic injury. Many adaptive responses occur during exposure to hypoxia to facilitate survival. It is possible that increased activity of the delta opioid receptor system is one such adaptation. We tested the hypothesis that mice exposed to prolonged hypoxia have increased expression of the delta opioid receptor in brain tissue. Prolonged exposure to hypoxia (9% oxygen, balance nitrogen) continuously for seven days selectively decreased delta opioid receptor expression in mouse brain homogenate. The same hypoxic treatment had no effects on either mu or kappa opioid receptor expression, indicating that this response was not due to non-selective degradation of protein. Shorter term hypoxic treatments (one day and three days) did not induce changes in delta opioid receptor expression in whole brain homogenate. Binding assays were also conducted in grossly dissected brain regions (cortex, midbrain, hindbrain) to determine whether the shorter term treatments would induce changes in receptor expression in more discrete areas. No consistent changes in delta opioid receptor expression were detected in these brain regions. These data demonstrate that opioid delta receptors are hypoxia sensitive and may be a part of an adaptive process to increase survival in the organism. One possible cause for the decrease in delta opioid receptor expression following seven days of hypoxic exposure may be receptor down-regulation caused by an increased release of endogenous substances acting at delta receptors. As delta opioid receptor agonists appear promising for therapeutic potential in management of hypoxic injury, changes in delta receptor expression in response to long-term hypoxia could impact potential utilization of delta agonists in patients suffering chronic hypoxia.

Animals↗
PubMed1996

Thermoregulatory effects of cyanide and azide in the toad, Bufo marinus.

An important adaptation to hypoxia is a regulated reduction in body temperature (Tb; anapyrexia), presumably because it lowers metabolic rate when oxygen supply is limited. Although this beneficial response occurs in organisms ranging from protozoans to mammals, little is known of the cellular mechanisms involved. We showed previously that inhibition of oxidative phosphorylation mediates hypoxia-induced anapyrexia in the paramecium. In this study, we tested the hypothesis that inhibition of oxidative phosphorylation also causes anapyrexia in a vertebrate, Bufo marinus. Tb in toads was measured in a thermal gradient 24 h before and 24 h after administration of either NaCN or NaN3, both inhibitors of oxidative phosphorylation. Subcutaneous NaCN (0.6 mmol/kg) reduced Tb from 29.1 +/- 0.8 to 19.6 +/- 0.6 degree C (P = 0.002). Infusion of NaCN (0.6 mumol/kg) into the fourth ventricle of the brain reduced Tb from 30.0 +/- 0.9 to 24.8 +/- 1.2 degrees C (P = 0.01). Responses to NaN3 were similar to the NaCN responses. Control injections and subcutaneous injections of 0.6 mumol/kg NaCN and NaN3 had no significant effect on Tb (P > 0.32). Neither NaCN nor NaN3 had significant effects on arterial PO2, PCO2, or pH at 26 degrees C. These results indicate that inhibition of oxidative phosphorylation in the central nervous system leads to the selection of cooler temperatures. Thus reduced oxidative phosphorylation within the brain may be an important factor eliciting hypoxia-induced anapyrexia.

Animals↗
PubMed1995

Lymphatic regulation of hematocrit during hypoxia in the toad Bufo woodhousei.

Hypoxia rapidly increases hematocrit (Hct) in anuran amphibians by reducing plasma volume, but the mechanism(s) mediating this response is unknown. We tested the hypothesis that, during hypoxia, plasma volume is reduced by impaired lymph heart (LH) function, decreasing lymph flow into the circulation. In Bufo woodhousei, we measured the effects of hypoxia on Hct, lymph heart rate (LHR), LH pressure, the movement of dye from the dorsal lymph sac to the arterial blood, and flow through an open LH cannula. We also tested whether splenic contraction or cholinergic nerves contribute to the hypoxia-induced changes. Graded hypoxia between 21 and 4% O2 produced graded increases in Hct (P < 0.0001) and decreases in LHR (P = 0.01). Hypoxia reduced the rate of increase in arterial Evans blue concentration after injection into the dorsal lymph sac (P = 0.041) and decreased flow through an open LH cannula (P < 0.012). Hypoxia increased Hct and reduced LHR similarly in control, splenectomized, and sham-splenectomized toads. Atropine had no significant effect on Hct and LHR. These results indicate that the LHs play a regulatory role in hypoxia-induced hemoconcentration.

Animals↗
PubMed1995

Central vascular flow patterns in the alligator Alligator mississipiensis.

Many different flow patterns have been described through the central circulation of crocodilian reptiles. We tested the hypothesis that the vagus nerve stimulation promotes right-to-left (R-L) shunting in the alligator. Flow patterns were investigated before and during stimulation of the intact left vagus nerve using three methods. 1) Atrial and aortic PO2 were measured simultaneously and continuously by gas probes. 2) Atrial outflows were tracked with a blood tracer (helium). 3) Flows were assessed with echocardiography. Four different flow patterns were observed before vagal stimulation: left ventricular (LV) blood flowed into both the right (RAo) and left (LAo) aortas, whereas right ventricular (RV) blood flowed only into the LAo; both aortas received a mixture of LV and RV blood; only LV blood perfused both aortas; and RV blood flowed into both aortas, but LV blood flowed only into the RAo. During vagal stimulation, both aortas received a mixture of LV and RV blood in half of the animals, and in the other half, both aortas received RV blood, but LV blood flowed only into the RAo. Doppler and contrast echocardiography demonstrated swirling flow in the foramen of Panizza and the base of the LAo during systole. These data indicate that vagal stimulation either maintains or produces R-L shunting, flow patterns are variable, and blood can swirl in the foramen of Panizza and LAo base.

Alligators and Crocodiles↗
PubMed1994

Interactions between cellular respiration and thermoregulation in the paramecium.

An important adaptation to hypoxia is a regulated reduction in body temperature because it lowers metabolic rate when oxygen supply is limited. Although this beneficial response occurs in organisms ranging from protozoans to mammals, little is known of the cellular mechanisms responsible for the hypoxia-induced reduction in temperature. Using the unicellular protozoan, Paramecium caudatum, we showed that inhibition of oxidative phosphorylation with sodium azide (NaN3) under normoxic conditions mimics the thermoregulatory effects of hypoxia, causing this species to select a lower temperature in a thermal gradient (P < 0.0001). Under control conditions, selected temperature (Tsel) was 28.3 +/- 0.3 degrees C. NaN3 concentrations of 0.1 mM and above significantly reduced Tsel (P < 0.0001). Ten millimolar NaN3 produced the maximal reduction in Tsel, 11.4 degrees C, and the dose that produced 50% of the maximal response was 0.7 mM. The reduction in temperature was beneficial because both O2 consumption and survival were significantly less affected by NaN3 at lower temperatures. These results suggest that O2 does not directly affect thermoregulation in the paramecium. Rather, the hypoxia-induced reduction in Tsel results from inhibition of oxidative phosphorylation.

Animals↗
PubMed1994

A new function for lactate in the toad Bufo marinus.

In the amphibian Bufo marinus, progressive hypoxia below a critical PO2 elicits a transient 50% increase in O2 consumption that coincides with the onset of lactate formation. The present study was designed to test the hypothesis that lactate causes the observed rise in metabolic rate. Arterial bolus infusions of pH-neutral sodium lactate solutions (4 mmol/kg body wt) in toads maintained under hypoxia actually elicit a similar increase in metabolic rate. The application of adrenergic antagonists (bretylium tosylate, phentolamine, propranolol, and reserpine) inhibits this response, suggesting that catecholamines are involved. Moreover, animals injected with lactate move to a cooler environment (behavioral hypothermia), a behavioral response that is beneficial during hypoxia. We hypothesize that, in accordance with Cannon's concept of an emergency response, lactate may function as an alarm signal during hypoxia. However, the signal function of lactate is observed in animals both under hypoxia and under normoxia and should thus be considered in future studies whenever elevated lactate levels are present, e.g., during and after exercise.

Alkalosis, Respiratory↗
PubMed1993

Vascular effects of arginine vasotocin in toad skin.

Fluid balance in amphibians is regulated, in large part, by arginine vasotocin (AVT). One important action of this hormone is to facilitate water uptake by increasing the water permeability of the skin. Cutaneous blood flow also affects water uptake, but the effects of AVT on skin perfusion are unknown. This study tested the hypothesis that AVT facilitates water uptake, not only by increasing cutaneous water permeability, but also by promoting cutaneous blood flow. The effects of AVT on blood flow through the ventral pelvic skin, a region specialized for water uptake, were assessed in Bufo marinus by determining the conductance of the skin to acetylene (GsAc), an index of cutaneous blood flow. A pump-perfused skin preparation was used to study the effects of AVT on the cutaneous vascular resistance (CVR) of the ventral pelvic skin and the dorsal skin (a region not normally involved in water uptake). Bolus AVT injections (iv) of 10 pmol/kg and below had no significant effect on GsAc (P > 0.45). However, 100 and 300 pmol/kg of AVT decreased GsAc by 39 +/- 7 (P < 0.001) and 63 +/- 6% (P < 0.001), respectively. The higher AVT doses increased mean arterial pressure. AVT increased CVR in both pump-perfused preparations. The lowest concentration of AVT tested that significantly raised CVR was 1 x 10(-10) M for the dorsal skin (P = 0.006) and 3 x 10(-10) M for the ventral pelvic skin (P = 0.038).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Behavioral hypothermia and survival of hypoxic protozoans Paramecium caudatum.

Hypoxia has been shown to elicit behavioral hypothermia in a number of different metazoan species, all with nervous systems. The protozoan, Paramecium caudatum, has no nervous system and was not expected to display behavioral hypothermia. However, this species was also found to select a lower temperature in a thermal gradient under hypoxic conditions. This response proved to be beneficial as survival of hypoxic paramecia was greatly increased at lower temperatures. This unicellular species may provide a useful model to investigate the cellular and molecular basis of adaptive thermoregulatory behavior.

Animals↗
PubMed1992

Mechanism of intracardiac shunting in the turtle Pseudemys scripta.

Two principal hypotheses account for right-left (R-L) intracardiac shunting in reptiles. The "pressure shunting" hypothesis proposes no functional separation between the ventricular cava during systole. The "washout shunting" hypothesis suggests that during systole, the cavum pulmonale (CP) is functionally separate from the rest of the ventricle. The purpose of this study was to test these hypotheses during control, after acetylcholine (ACh) administration, after epinephrine (Epi) administration, and during apnea. Anesthetized (pentobarbital) turtles (Pseudemys scripta) were mechanically ventilated and three nonocclusive catheters were implanted into the right atrium (RAt), left atrium (LAt), and CP. In addition, three blood gas catheters connected to a mass spectrometer were implanted into the RAt, LAt, and right or left aortic arch for measurement of PO2. A tracer gas, He dissolved in saline, was sequentially injected into the three cardiac chambers and was detected by the mass spectrometer. The presence of R-L shunting was assessed with the blood PO2 and PHe measurements. ACh produced R-L shunting in all animals. No R-L shunting occurred after Epi administration and 20 min of apnea. In all animals after ACh administration, He was detected in an aorta after He infusion in the RAt and LAt, but never after infusion of He into the CP. These results from this preparation are inconsistent with the pressure hypothesis and support the washout hypothesis of intracardiac shunting.

Acetylcholine↗
PubMed1992

Effects of capillary red cell density on gas conductance of frog skin.

We tested experimentally the hypothesis that decreasing capillary red blood cell (RBC) density (dRBC) reduces the tissue diffusing capacity of frog skin to CO (DtiCO) and O2 (DtiO2). The effects of dRBC on CO2 transport were also assessed. C18O, O2, and CO2 transport between the skin and a cutaneous sample chamber on the belly of anesthetized (halothane) frogs (Rana pipiens) was measured by mass spectrometry, and the cutaneous conductances to C18O (GCO), O2 (GO2), and CO2 (GCO2) were calculated. The dRBC of the planar cutaneous capillary bed was measured by intravital fluorescent video microscopy. DtiCO and DtiO2 were calculated from a modification of the Roughton-Foster equation: 1/G = 1/Dti + 1/(theta RBC.dRBC), where theta RBC values were estimated from literature values. In one group of animals (n = 6), measurements were made before hemodilution (dRBC = 630 +/- 56 cells/mm2), after one hemodilution (dRBC = 349 +/- 50 cells/mm2), and after a second hemodilution (dRBC = 150 +/- 31 cells/mm2). In controls, time had no effect on GCO, GO2, or GCO2 (P greater than 0.42). Before hemodilution, GCO, GO2, and GCO2 were 0.069 +/- 0.010, 0.088 +/- 0.0012, and 1.23 +/- 0.010 nmol.min-1.Torr-1.cm-2, respectively, and lowering dRBC by hemodilution decreased all these parameters (P less than 0.025). The mean slopes of GCO, GO2, and GCO2 vs. dRBC were 6.0 +/- 1.3 x 10(-7), 7.2 +/- 2.3 x 10(-7), and 7.8 +/- 3.0 x 10(-6) nmol.min-1.Torr-1.RBC-1, respectively. Lowering dRBC also decreased DtiCO and DtiO2 (P less than 0.034). DtiCO and DtiO2 were 0.080 +/- 0.012 and 0.096 +/- 0.013 nmol.min-1.Torr-1.cm-2, respectively, before hemodilution. The mean slopes of DtiCO and DtiO2 vs. dRBC were 4.9 +/- 2.1 x 10(-7) and 6.5 +/- 2.8 x 10(-7) nmol.min-1.Torr-1.RBC-1, respectively. Hemodilution had no effect on perfused capillary density (P = 0.38). These results indicate that tissue diffusive conductance is proportional to dRBC. Regulation of dRBC may be an important mechanism modulating diffusive gas transport in tissue.

Animals↗
PubMed1991

Behavioral thermoregulation of the toad, Bufo marinus: effects of air humidity.

Two experiments were performed. The first tested the hypothesis that the toad, Bufo marinus, will select a lower ambient temperature under dry environmental conditions. This behavioral response would reduce evaporative water loss and facilitate survival on land. The second experiment measured the effects of temperature on evaporative water loss. In the first experiment, toads were placed in a thermal gradient (11-40 degrees C) for 3 days. On days 1 and 3, water-filled dishes were placed along the temperature gradient and humid air was circulated through the chamber. On day 2, water dishes were removed, and dry air was circulated through the chamber. Body temperature (Tb) was recorded with a cloacal thermistor. Selected Tb was approximately 8.6 degrees C lower during the dry conditions than during the humid conditions. The behavioral hypothermia took about 6 h to develop. In the second experiment, a reduction in Tb from 17.7 to 12 degrees C reduced evaporative water loss by 42%. Consequently, behavioral hypothermia of the toad is an important adaptation to dry environmental conditions.

Animals↗
PubMed1991

Physiological significance of behavioral hypothermia in hypoxic toads (Bufo marinus).

We tested the hypotheses that hypoxic toads (Bufo marinus) in a thermal gradient would select a lower than normal temperature and that this behavioral response would be beneficial. Under normoxic conditions, selected body temperature was 24.2 +/- 3.6 degrees C. When inspired O2 was 10% or less, mean selected temperature decreased to 15.3 +/- 2.4 degrees C. The theoretical advantages of hypoxia-induced hypothermia we tested include (1) a reduction of oxygen uptake (VO2) by a Q10 effect; (2) increased arterial saturation (SaO2), (3) a decreased ventilatory response, and (4) a decreased stress response. Gas exchange, hematocrit, hemoglobin, SaO2, PaO2 and pH were measured at 25 degrees C (normal preferred temperature) and 15 degrees C (hypoxia preferred temperature) in toads breathing normoxic or hypoxic gas mixtures. During graded hypoxia at 15 degrees C, SaO2 was significantly increased and VO2 was significantly reduced compared with 25 degrees C. Graded hypoxia did not significantly affect VO2 at 25 degrees C, despite evidence for increased ventilation at that temperature (increased pH and respiratory exchange ratio, RE). At 15 degrees C, graded hypoxia had a significant effect on VO2 only at an inspired O2 of 4%. Increased RE with hypoxia was significant at 25 degrees C but not at 15 degrees C. Hematocrit and [hemoglobin] rose significantly during graded hypoxia at 25 degrees C but did not change at 15 degrees C. Toads exposed to 10% O2 (the value that elicits behavioral hypothermia) showed a significant respiratory alkalosis at 25 degrees C but not at 15 degrees C. Likewise, hypoxia caused a significant drop in SaO2 and PO2 at 25 degrees C. Cooling to 15 degrees C during hypoxia caused a significant rise in SaO2 but no change in PaO2. In conclusion, behavioral hypothermia is a beneficial response to hypoxia in Bufo marinus.

Acid-Base Equilibrium↗
PubMed1990

Autonomic regulation of cutaneous vascular resistance in the bullfrog Rana catesbeiana.

To gain a better understanding of the regulation of cutaneous blood flow in the bullfrog, the vascular innervation, vasoactivity and adrenoceptor types of the cutaneous vasculature were investigated using a pump-perfused skin preparation. Stimulation of cranial nerve I, the vagal ganglion, sympathetic ganglion 1 and sometimes sympathetic ganglion 2 caused cutaneous vascular resistance (CVR) to increase. Stimulation of cranial nerve IX and spinal nerves 1 and 2 had no effect on CVR. The response to stimulation of sympathetic ganglion 1 was antagonized by phentolamine but not by atropine. Phentolamine, atropine and alpha,beta-methylene ATP had no effect on the response to vagal stimulation. Both epinephrine (EPI) and norepinephrine (NE) increased CVR, with EPI being more potent than NE. The minimum concentrations of EPI and NE required for a significant change in CVR were much higher than plasma catecholamine levels reported for resting bullfrogs. Phentolamine antagonized, but propranolol had no effect on, the responses to the catecholamines. Isoproterenol caused small decreases in CVR which were abolished by propranolol. Acetylcholine was a weak vasodilator. The results indicate that the cutaneous vasculature has two types of vasomotor nerves: sympathetic nerves that are probably adrenergic, and other nerves that are non-adrenergic/non-cholinergic and which do not use ATP as a transmitter. Although catecholamines are vasoactive, the sensitivity of the cutaneous vasculature to EPI and NE is probably too low to allow a direct regulatory role of these hormones on CVR. There is no evidence for cholinergic regulation of CVR. Both alpha- and beta-adrenoceptors are present in the cutaneous vasculature. alpha-Adrenoceptors mediate the constrictor responses to sympathetic nerve stimulation and catecholamine administration. It is unlikely that beta-adrenoceptors play a significant role in regulating CVR.

Acetylcholine↗
PubMed1989

Effects of environmental O2 on blood flow and diffusing capacity in amphibian skin.

The effects of local environmental PO2 on cutaneous blood flow (Q) and the membrane diffusing capacity of the skin (D) were investigated in the leopard frog, Rana pipiens, and the lungless salamander, Desmognathus quadramaculatus. Halothane anesthetized animals were equilibrated with Freon-22 (Fr) and acetylene (Ac) in a box. A gas mixture containing either 0, 20 or 40% O2, respectively, in N2 and initially free of Fr and Ac was drawn through a small sample chamber on the abdomen. The excretion of Fr and Ac into the chamber was analyzed with a mass spectrometer. These conditions allowed the determination of the cutaneous conductance to Fr (GFr) and Ac (GAc) at the 3 levels of local environmental O2. GFr and GAc of the isolated skin and the blood solubilities of the 2 gases were also determined. To estimate Q, DAc and DFr, the data were analyzed with a homogeneous single capillary model. In the frog, Q varied directly with sample chamber [O2], but chamber [O2] had no effect on D. In the salamander, O2 had no effect on either Q or D. The results indicate that regulation of cutaneous gas exchange in the frog by local environmental O2 only involves alterations in Q. Similar control of cutaneous gas exchange is absent in the lungless salamander.

Acetylene↗
PubMed1989

Estimation of blood flow distribution in skeletal muscle from inert gas washout.

A new method is evaluated for the estimation of blood flow-to-volume distribution in skeletal muscle from inert gas washout kinetics. Acetylene washout from the isolated, blood-perfused canine gracilis muscle was measured continuously with a blood gas catheter in combination with a mass spectrometer. The washout curves were transformed to flow-to-volume ratio distributions by means of a 50-compartment model. The algorithm fits the expression for the washout curve derived from the model by a least-squares method with enforced smoothing. The algorithm was evaluated using computer simulations in which artificial washout curves were generated by a multicompartment model with a known flow distribution. A wide range of given flow distributions could be recovered from the simulated data. The data were also analyzed using a linear programming technique. Analysis of the experimental data with the least-squares method showed that there is considerable heterogeneity in the distribution of perfusion in resting gracilis muscle. The distribution is characterized by at least two modes and a single compartment with a very low perfusion-to-volume ratio. Experimental noise made it impossible to obtain feasible flow distributions by means of linear programming.

Acetylene↗