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Biomedical subjects

M Rundgren

Publications and source records attributed to M Rundgren.

At least 37 records · Page 2Linked to original sources
PubMed1994

Hypertension and thirst outlasting renal vasoconstriction as effects of a brief evaluation of systemic angiotensin II in sheep.

The influence of 10 min intracarotid (i.c.) and intravenous (i.v.) infusions of angiotensin II (Ang II; 20 pmol kg-1 min-1) on carotid blood pressure (cBP) and renal blood flow (RBF) was studied in unanaesthetized ewes without and with pre-treatment with the alpha 1- and beta-adrenoceptor blocker labetalol. RBF was also monitored during 30 min intracerebroventricular (ICV) infusions of Ang II at 2 pmol kg-1 min-1. The i.c. infusions of Ang II induced about 50 mmHg rise in cBP. A steep decline occurred during 5 min post-infusion, followed by a much slower reduction with the cBP remaining above control level at 40 min post-infusion. The pressure elevation induced by i.v. Ang II was less pronounced but exhibited a similar pattern. Labetalol significantly reduced the pressor response to i.c. as well as i.v. Ang II. The i.c. and i.v. infusions of Ang II conspicuously reduced the RBF regardless of whether the ewes were labetalol-treated or not. At 5 min after the infusions RBF had returned to control level. The ICV infusions did not influence the RBF. Ang II i.c. elicited thirst in 50% of the ewes with the urge to drink remaining at 40 min post-infusion. The dipsogenic response was not reduced by labetalol pretreatment. The results imply that no cerebral component contributes to the reduction in RBF induced by systemic Ang II. However, a centrally mediated action seems to be the cause of the long-lasting post-infusion cBP elevation and dipsogenic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1994

Inefficiency of intracerebroventricular ANP to alter haemodynamic, plasma vasopressin and renin responses to haemorrhage in sheep.

Whether intracerebroventricular (i.c.v.) infusion of atrial natriuretic peptide (human-ANP, 1-28) 25 pmol min-1 influences the tolerance to blood loss and haemorrhage induced cardiovascular, vasopressin and renin responses were studied in five conscious sheep. The i.c.v. infusion was started 60 min prior to a slow (0.7 ml kg-1 min-1) venous haemorrhage, was run concurrently with bleeding, and for 90 min thereafter. Venous blood was removed until the mean systemic arterial pressure suddenly fell to about 50 mmHg. There were no statistically significant differences in either the bleeding volume necessary to induce the sudden decrease in blood pressure, or in cardiovascular parameters measured by venous heart thermodilution catheterization, compared with control experiments with i.c.v. infusion of artificial CSF. The plasma protein and vasopressin concentrations and renin activity were unaffected by the i.c.v. infusion of ANP as were the changes in these parameters occurring during the subsequent haemorrhage. The same negative findings were obtained with a three times higher dose of ANP(1-28) (75 pmol min-1), tested in three of the animals. Thus the i.c.v. infusion of ANP(1-28), in amounts expected to elevate the CSF concentration far above basal levels does apparently not influence normal blood pressure regulation or alter haemodynamic, vasopressin and renin responses to haemorrhage in conscious sheep.

Animals↗
PubMed1994

Cerebral osmoregulatory reduction of plasma renin concentration in sheep.

A centrally mediated inhibitory influence of plasma hypertonicity on renin secretion was investigated in conscious, Na-depleted sheep. Infusions of hypertonic solutions were made into the carotid artery or jugular vein, and the effects on plasma renin concentration (PRC) compared. Intracarotid infusion of 1.65 M NaCl significantly reduced PRC (to 74% of the pre-infusion value) within 15 min of the commencement of the infusion whereas corresponding intrajugular infusion did not. Intracarotid infusion of 3 M sorbitol for 45 min also reduced PRC (to 64% of the pre-infusion level) significantly after 15 min of infusion. By contrast, neither intrajugular infusion of 3 M sorbitol, nor intracarotid infusion of isotonic 0.15 M NaCl for 45 min significantly reduced PRC. Intracarotid infusion of hypertonic sorbitol for 45 min did not inhibit PRC in sheep with cerebral lesions of the lamina terminalis. These results show that plasma hypertonicity may have an inhibitory influence on renin secretion. The inhibition is probably mediated by an effect of hypertonicity on the CNS, rather than a direct effect on the kidney.

Animals↗
PubMed1994

Haemodynamic responses to hypotensive haemorrhage in conscious sheep with emphasis on renal and femoral blood flow.

Haemodynamic responses to slow (0.7 ml kg-1 min-1) haemorrhage were investigated in eight adult conscious sheep, fitted with permanent ultrasonic flow probes around the renal and femoral artery. The haemorrhage was continued until the mean systemic arterial pressure (MSAP) suddenly dropped to about 50 mmHg. The spontaneous recovery was followed for 60 min and then the blood was retransfused. A distinct fall in MSAP was obtained after 14.5 +/- 0.9 ml blood (kg body weight)-1 (24% of the estimated blood volume) had been removed, but the interindividual differences were rather large (range, 10.2-18.1 ml kg-1). Therefore, the haemodynamic responses during haemorrhage were related to the total bleeding volume and not to time or volume per kilogram body weight. Before 90% of the total haemorrhage volume had been removed, the MSAP decreased gradually, reaching statistical significance at 80% (P < 0.05). At end of bleeding the cardiac output (CO) had fallen from a pre-haemorrhage level of 4.7 +/- 0.2 to 2.9 +/- 0.2 1 min-1. Although the femoral blood flow (FBF) was largely unaffected by the haemorrhage, and thus increased as a fraction of CO, the total systemic vascular resistance was markedly increased during the post-haemorrhage period, indicating a longer lasting elevation of vascular resistance in other vascular beds. In spite of a concomitant marginal decrease in renal blood flow (RBF), the renal vascular resistance (RVR) was unchanged until 90% total haemorrhage had occurred. At the same time as blood pressure fell, RBF decreased markedly, concomitant with a transient increase in RVR, which was followed by a decrease towards basal levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Zonation of acetaminophen metabolism and cytochrome P450 2E1-mediated toxicity studied in isolated periportal and perivenous hepatocytes.

To study the mechanism of centrilobular damage developing in the centrilobular region after high doses of acetaminophen (APAP), its metabolism and toxicity were compared in periportal and perivenous hepatocytes isolated by digitonin/collagenase perfusion. Contrary to earlier reports, based on perfusions, no evidence for a periportal dominance of APAP sulfation could be observed. Glucuronidation, the dominant pathway of conjugation at high (5 mM) APAP concentration, was faster in perivenous cells. During primary culture, prolonged exposure (> or = 24 hr) to 5 mM APAP damaged perivenous cells, with a higher P450 2E1 level than periportal cells. When cells were isolated from ethanol-pretreated rats, to induce P450 2E1 levels specifically in the perivenous region, perivenous hepatocytes exhibited enhanced APAP vulnerability and extensive glutathione depletion. In contrast, corresponding periportal cells retained good viability. Isoniazid, an inhibitor of cytochrome P450 2E1, protected cells against APAP toxicity and prevented glutathione depletion. Induction of P450 2E1 also caused a 3-fold increase in the covalent binding of reactive intermediates from [14C]APAP, and this increase was mainly confined to perivenous cells. These results indicate that in rat liver there is only slight perivenous zonation of APAP conjugation and suggest that zone-specific APAP activation, mediated by the regional expression of ethanol-inducible cytochrome P450 2E1, is responsible for the characteristic centrilobular liver damage elicited by APAP.

Acetaminophen↗
PubMed1993

Intracerebroventricular infusion of glycine stimulates vasopressin release in conscious sheep.

We have previously observed that elevation of the plasma glycine concentration stimulates vasopressin (AVP) release in man and sheep. In the present study we show that this effect of glycine can be elicited directly via a cerebral site of action in conscious sheep. Intracerebroventricular infusions of 0.05 and 0.15 M glycine solutions increased the plasma AVP concentration by 6 and 50 times, respectively, while no effect on water intake was observed. Hyperhydration did not block the stimulation of AVP release. No behavioural side effects, or changes in blood pressure, were observed in response to the infusions.

Analysis of Variance↗
PubMed1993

Haemodynamics and fluid balance after intravenous infusion of 1.5% glycine in sheep.

With the aim of studying the pathophysiological background of the "TUR syndrome", we gave six conscious ewes an intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min. Isotonic saline infusions served as controls. Central haemodynamics were monitored. The plasma concentrations of protein, K, Na and vasopressin, and plasma osmolality were measured repeatedly for up to 4 h. The urinary excretions of Na, K and osmoles were also followed. Both infusions caused an elevation of the mean arterial pressure. With glycine, the pressure increased from 93 +/- 4 to 112 +/- 12 mmHg (12.4 +/- 0.5 to 14.9 +/- 1.6 kPa) (mean +/- s.d.). The pulmonary capillary wedge pressure increased from 7 +/- 3 to 16 +/- 3 mmHg (0.9 +/- 0.4 to 2.1 +/- 0.4 kPa) and remained slightly elevated. The central venous pressure rose from 2 +/- 3 to 11 +/- 3 mmHg (0.3 +/- 0.4 to 1.5 +/- 0.4 kPa) but returned to baseline within 30 min after the infusion. Infusion of glycine resulted in a decrease in the plasma Na concentration from 144 +/- 3 to 114 +/- 4 mmol/l. The plasma osmolality decreased from 290 +/- 2 to 280 +/- 1 mosmol/l, and remained low. There was a median 6-fold increase in plasma vasopressin concentration, while saline did not elicit vasopressin release. Despite the absence of electrolytes in glycine solution, the urinary excretion of sodium amounted to 106 +/- 40 mmol. We conclude that i.v. infusion of 1.5% glycine solution in sheep causes a transient circulatory strain and natriuresis. Moreover, a vasopressin-mediated reduction of maximal water excretion contributes to persisting hypoosmolality.

Amino Acids↗
PubMed1993

Effects of reduced CSF Na concentration and osmolality on haemodynamic and humoral responses to hypotensive haemorrhage in conscious sheep.

The effects of iso- and hypo-osmotic reduction of the CSF [Na+] on the tolerance to blood loss and concomitant cardiovascular and humoral responses were studied in conscious sheep. Animals only subjected to haemorrhage served as controls. The changes in CSF composition were induced by intracerebroventricular infusions of 0.3 M mannitol, respectively, 0.04 M NaCl. In the former instance the CSF [Na+] was reduced by 18 mM whereas a lowering by 13 mM concomitant with decreased CSF osmolality (mean change 25 mOsm kg-1) was seen in response to the NaCl solution. Apart from a slight lowering of the cardiac output during the infusion of 0.3 M mannitol preceding haemorrhage, the changes in CSF composition did not have any significant haemodynamic effects in the normovolaemic animal, or altered the cardiovascular responses to a subsequent hypotensive haemorrhage. The amount of blood needed to be withdrawn to obtain the predefined degree of hypotension did not differ significantly between treatment groups. The plasma vasopressin and angiotensin II concentrations were consistently increased by the hypotensive haemorrhage, but the magnitude of the vasopressin response was significantly reduced when the CSF [Na+] was lowered. We conclude that lowered CSF [Na+] and/or osmolality, in contrast to increased CSF [Na+], does not influence the tolerance to blood loss or the accompanying haemodynamic changes in sheep, in spite of an attenuated vasopressin response.

Angiotensin II↗
PubMed1992

Hemodynamic effects of vasopressin antagonism and angiotensin I converting enzyme inhibition during halothane anesthesia in sheep.

The hemodynamic effects of separate and combined intravenous administration of the vasopressin (AVP) V1-receptor antagonist SK&F 100273 (10 micrograms/kg) and the angiotensin I converting enzyme inhibitor captopril (20 mg + 1 mg/h) were studied in 12 sheep during stable halothane anesthesia (1.5% end-tidal conc.). The separate blockade of either V1-receptors or angiotensin II (ANG II) synthesis induced a small (7-10%), but significant, fall in mean systemic arterial pressure (MSAP), whereas the combined treatment caused a 30% reduction in blood pressure. The changes in systemic vascular resistance paralleled those of the MSAP. Consequently, the cardiac output was largely unaffected by the interference with AVP effects and/or ANG II synthesis. The halothane anesthesia effectively increased the plasma levels of AVP and ANG II, and plasma renin activity without any relation to changes in MSAP. When either the AVP effects or ANG II synthesis were blocked separately, there was a slight tendency for a compensatory increase of the unimpeded hormonal system. It is concluded that halothane anesthesia increases the plasma levels of AVP and ANG II in sheep, and that the maintenance of the arterial pressure is dependent on the concurrent vasopressor effects of the two hormones in this situation.

Anesthesia, Inhalation↗
PubMed1992

Cardiovascular and renal effects of intracerebroventricular angiotensin II in conscious sheep.

Effects on systemic and pulmonary haemodynamics, renal electrolyte excretion, and plasma concentration of vasopressin, catecholamines, electrolytes and proteins in response to intracerebroventricular infusions of [Val5]-angiotensin II (ANG II) at 1, 2 and 4 pmol kg-1 min-1 in isotonic saline for 30 min were studied in conscious sheep (n = 6). Vehicle control infusions were performed in four of the animals. All three doses of ANG II were expected to increase CFS concentration of the peptide above physiological levels. All ANG II infusions were noticed to be dipsogenic, but the animals were not allowed to drink freely until at the end of the experiments (at 120 min post-infusion). The systemic arterial blood pressure increased significantly only in response to 2 and 4 pmol kg-1 min-1, concomitant with an increase of the systemic vascular resistance, whereas the cardiac output and heart rate remained unchanged. The central venous pressure increased only after administration of the highest ANG II dose, while pulmonary artery, and capillary wedge pressures were unaffected during all experiments. The plasma protein and K concentration fell in response to ANG II administration. Also here, the effects were significant only at 2 and 4 pmol kg-1 min-1. The plasma levels of vasopressin, noradrenaline, adrenaline and dopamine did not change significantly in response to any of the infusions. The renal Na excretion increased by 100-400%, but not in a strictly dose-dependent manner. Much smaller and more variable effects were seen on the renal K excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Increased resistance to haemorrhage induced by intracerebroventricular infusion of hypertonic NaCl in conscious sheep.

The effect of elevated cerebrospinal fluid Na+ concentration (CSF [Na+]) on the tolerance of blood loss, and concomitant cardiovascular and humoral responses were studied in conscious sheep. A slow (0.7 ml kg-1 min-1) venous haemorrhage was continued until the mean systemic arterial pressure suddenly decreased to less than 50 mmHg, or in the absence of hypotension, until a total blood loss of 25 ml kg-1. Significantly more blood had to be removed to induce hypotension in animals receiving an intracerebroventricular (i.c.v.) infusion (0.02 ml min-1) of 0.5 M NaCl (starting 30 min before haemorrhage and continued throughout the experiment) compared to control haemorrhages without concomitant i.c.v. infusion (22.7 +/- 1.2 ml vs 16.9 +/- 0.9 ml kg-1). In one animal, subjected to 0.5 M NaCl infusion, the blood pressure was still maintained at 25 ml kg-1 of haemorrhage. In spite of a larger blood loss, animals receiving i.c.v. infusion of hypertonic NaCl had an improved recovery of the blood pressure after haemorrhage, due to a better maintained cardiac output rather than to a reinforced increase of the vascular resistance. The improved cardiovascular responses to haemorrhage during elevated CSF [Na+] are not readily explained by the effects on the plasma concentrations of vasopressin, angiotensin II or noradrenaline, although the latter was augmented. The plasma protein concentration decreased already during the 30 min of hypertonic NaCl infusion preceding haemorrhage, and the haemodilution caused by the subsequent blood removal was aggravated, which indicates that this treatment also causes transfer of fluid to the plasma compartment. We conclude that elevated CSF [Na+] increases tolerance to haemorrhage and improves cardiovascular function after blood loss in sheep. Since the haemodynamic responses in many respects were similar to those reported in response to the systemic administration of a small volume of hypertonic NaCl solution in haemorrhagic shock, part of the effect of that treatment may be mediated via cerebral effects of increased Na+ concentration.

Angiotensin II↗
PubMed1992

Tolerance to haemorrhage during vasopressin antagonism and/or captopril treatment in conscious sheep.

The effect of separate and combined blockade of vasopressin (AVP) V1-receptors and angiotensin II formation on resistance to a slow venous haemorrhage (0.7 ml kg-1 min-1) was studied in six conscious adult sheep by bleeding to the point of an abrupt fall in the mean systemic arterial pressure (MSAP). Intravenous administration of the V1-receptor antagonist [d(CH2)5Tyr(Me)AVP] (10 micrograms kg-1) and/or the angiotensin I converting enzyme inhibitor captopril (20 mg + 1 mg h-1) did not cause any significant haemodynamic changes in the normovolaemic animal. The volume of haemorrhage necessary to induce acute hypotension (MSAP < 50 mmHg) was significantly smaller after AVP blockade alone (13.8 +/- 0.7 ml kg-1; P < 0.01) but not after captopril treatment (14.7 +/- 1.6 ml kg-1; n.s.) compared to control animals receiving no drug treatment (16.8 +/- 0.6 ml kg-1). The combined treatment with the AVP antagonist and captopril caused a further decrease in tolerance to haemorrhage (9.4 +/- 1.2 ml kg-1; P < 0.001). Blockade of AVP V1-receptors was associated with an attenuated increase in systemic vascular resistance immediately after the end of haemorrhage, concomitant with an accentuated lowering of the central venous pressure. In contrast, captopril treatment decreased the degree of vasoconstriction mainly during the second half of the posthaemorrhage observation period of 1 hour. It is concluded that both AVP and angiotensin II contribute to the maintenance of the MSAP during haemorrhage in conscious sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

Relationship of membrane fluidity, chemoprotection, and the intrinsic toxicity of butylated hydroxytoluene.

In isolated rat hepatocytes, many chemicals elicit toxicity which is inhibitable by antioxidants such as butylated hydroxytoluene (BHT). Although BHT protection is evident at concentrations of less than about 50 nmol/mg protein, higher concentrations exhibit intrinsic concentration-dependent toxicity, which involves mitochondrial dysfunction. We evaluated the possibility that both chemoprotection and intrinsic toxicity could be explained by a common mechanism involving alterations in the physical properties of cellular membranes. In the red blood cell (RBC) osmotic fragility assay, BHT at less than 60 nmol/mg protein protected against osmotic fragility; however, BHT at higher concentrations enhanced osmotic fragility such that total osmolysis occurred at 135 nmol/mg. The BHT-mediated alterations in osmotic fragility correlated with changes in membrane fluidity, determined by fluorescence polarization of the hydrophobic probe 1,6-diphenyl-1,3,5-hexatriene. Protection from osmolysis correlated with decreased fluidity, while enhanced RBC fragility correlated with increased fluidity. In rat hepatocyte suspensions, high BHT concentrations also permeabilized the plasma and mitochondrial membranes to enzyme leakage, and these effects were accompanied by enhanced membrane fluidity. Although other mechanisms may be operative, alterations in membrane fluidity appear to be, in part, responsible for the observed chemoprotective effects at low concentrations, and intrinsic toxicity at higher concentrations of BHT.

Animals↗
PubMed1991

Effects of 1.5% glycine solution with and without 1% ethanol on the fluid balance in elderly men.

Ten male patients scheduled for transurethral prostatic resection (aged 57-79) were given irrigating fluid by intravenous infusion at 50 ml.min-1 over 20 min. Each patient was subjected to two infusions: 1.5% glycine in water on one occasion, and the same solution but with 1% ethanol added on the other. Urine and blood samples were collected at regular intervals for up to 2 h after infusion, and the changes in the distribution of water and electrolytes between fluid compartments were calculated. Transient prickling skin sensations were frequently reported effects of the infusions. Two patients experienced visual disturbances. There were no changes in the blood ammonia and plasma vasopressin levels. During the infusions, the estimated blood volume and the total plasma sodium and potassium content increased. The solutions produced osmotic diuresis with increased urinary excretion of water and electrolytes. After ending the fluid administration, blood volume was rapidly restored. Over the following 120 min the irrigant water was redistributed intracellularly or removed by urinary excretion. The addition of ethanol did not alter the overall effects of glycine solution on the fluid balance.

Absorption↗
PubMed1991

Haemodynamic and humoral responses to repeated hypotensive haemorrhage in conscious sheep.

Haemodynamic and humoral responses to two subsequent hypotensive haemorrhages, separated by 3 hours and each followed by retransfusion, were studied in unanaesthetized sheep. Haemorrhage was induced by removal of blood from a jugular vein at a rate of 0.7 ml kg-1 min-1 until the mean systemic arterial pressure suddenly decreased by 35 mmHg or more. In addition to the mean systemic arterial pressure, the cardiac output, the mean pulmonary arterial pressure, the central venous pressure and the pulmonary capillary wedge pressure decreased in response to each haemorrhage. The recovery of the systemic and pulmonary arterial pressure was slower and/or less efficient after the second haemorrhage, due to a less pronounced increase of the vascular resistance. Relative bradycardia, in association with the abrupt fall of the mean systemic arterial pressure, was more apparent during the first haemorrhage. The plasma levels of vasopressin, renin activity and angiotensin II were increased by each blood removal, but the vasopressin response to the second haemorrhage was significantly reduced. The plasma noradrenaline concentration was slightly and transiently elevated only in response to the second haemorrhage. The concentration of neuropeptide Y-like immunoreactivity in plasma was unaffected by both haemorrhages. It is suggested that the reduced and delayed increase in the systemic vascular resistance, accompanied by impaired recovery of the arterial pressure, and the relative absence of 'bleeding bradycardia', during the second haemorrhage, were due to the diminished vasopressin response.

Animals↗
PubMed1990

Oxidant-induced changes in the cellular energy homeostasis. A study with 3,5-dimethyl N-acetyl-p-benzoquinone imine and isolated hepatocytes.

Exposure of isolated hepatocytes to 400 microM 3,5-dimethyl N-acetyl-p-benzoquinone imine (3,5-diMe NAPQI), rapidly induced the formation of plasma membrane blebs. More than 50% of the viable cells were affected after 1 min incubation with 3,5-diMe NAPQI. Rapid loss of mitochondrial ATP, and sequential increases in ADP and AMP accompanied hepatocyte blebbing. 3,5-diMe NAPQI also induced a pronounced elevation of mitochondrial NADP level, whereas the NAD concentration was unaffected. Similar alterations in the adenine and pyridine nucleotide pools were found to occur in the cytosol, although at slower rates. During the initial phase of ATP loss and NADP production, there was also a concomitant decrease in the oxygen uptake of the hepatocytes. The decreases in energy substrates occurred in parallel to an increased uptake of trypan blue into the cells. Treatment of the hepatocytes with dithiothreitol, following 4 min exposure of the cells to 3,5-diMe NAPQI, reversed the quinone imine-induced changes in nucleotide levels and reduced the cytotoxicity. It is concluded that alteration of mitochondrial function, which results in changes in the cellular energy homeostasis, is an important event in the development of cytotoxicity caused by 3,5-diMe NAPQI.

Adenosine Triphosphate↗