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PubMed1995

Systemic hemodynamic and regional circulatory effects of centrally administered endothelin-1 are mediated through ETA receptors.

Central endothelin (ET) has been implicated in the regulation of the cardiovascular system. The effect of intracerebroventricular (i.c.v.) administration of ET-1 or IRL 1620 (5, 15 and 45 ng) on the systemic hemodynamics and regional circulation was studied in anesthetized rats using a radioactive microsphere technique. Systemic hemodynamics and regional blood circulation were determined before (baseline) and at 30 min after the injection of each dose of ET-1 or IRL 1620. Administration of saline (5 microliters, i.c.v.) did not produce any significant cardiovascular effects. The lower doses of ET-1 (5 and 15 ng) did not produce any significant effect on blood pressure (BP), heart rate (HR), cardiac output (CO), stroke volume (SV), total peripheral resistance (TPR) and regional blood circulation. However, the higher dose (45 ng) produced a transient rise (26%) followed by a sustained fall (48%) in BP. The decrease in BP was accompanied by significant decreases in CO (44%) and SV (39%), while HR and TPR were not affected. ET-1 (45 ng, i.c.v.) also produced a significant reduction in blood flow to the brain (75%), heart (49%), kidneys (66%), GIT (40%), portal system (52%) and musculo-skeletal system (38%), while blood flow to the skin was not affected. To determine pharmacological specificity of the central effects of ET-1, studies were performed in rats pretreated with BQ-123, a specific ETA receptor antagonist. Pretreatment with BQ-123 (10 micrograms, i.c.v.), 15 min prior to the administration of ET-1, completely antagonized the systemic hemodynamic as well as the regional circulatory effects of ET-1 (45 ng, i.c.v.). In order to determine whether stimulation of central ETB receptors produces any cardiovascular effects, studies were performed using IRL 1620, a specific ETB receptor agonist. Administration of IRL 1620 (5, 15 and 45 ng, i.c.v.) did not produce any effect on systemic hemodynamics and regional blood circulation in rats. It is concluded that ETA but not ETB receptors are involved in the central cardiovascular actions of ET.

Animals↗

PubMed1992

The WD-40 repeat.

An amino acid sequence motif, called the WD-40 repeat, has been found as a repeat in a large variety of proteins that do not share any obvious functional properties. At present, the function of the repeated motif is not known for any of these proteins. Interestingly, recent experiments in yeast indicate that several proteins containing the WD-40 repeat are genetically associated with members of the TPR-family, a protein family that is characterized by the presence of another repeated motif of unknown function: the tetratricopeptide repeat. It is conceivable that proteins containing the WD-40 repeat interact physically with members of the TPR-family via their respective repeated motifs.

Amino Acid Sequence↗

PubMed1981

Beta-adrenergic influence on cardiac dynamics during shock-avoidance in dogs.

The role of beta-adrenergic receptors in the mediation of the cardiodynamic effects of a shock-avoidance task was evaluated in conscious dogs with the cardioselective beta-adrenergic antagonist practolol. The animals were chronically instrumented for the measurement of peak rate of change of left ventricular pressure (LV dP/dt), heart rate (HR), cardiac output (CO), systolic (SPB) and diastolic (DBP) blood pressure and total peripheral resistance (TPR), and were each subjected to brief bouts of shock-avoidance with and without practolol pretreatment (2-4 mg/kg). Shock-avoidance evoked reliable increases of LV dP/dt, HR, CO, SBP and DBP, and decreases of TPR. Beta-adrenergic blockade virtually eliminated LV dP/dt increases, attenuated HR and CO increase as well as the vasodilatation, diminished SBP increases in certain animals but did not affect DBP increases. Stable interindividual differences in the magnitude of LV dP/dt and HR increases during shock-avoidance were demonstrated; these differences were abolished by beta blockade. These findings indicate that a beta-adrenergic mechanism accounted for most of the rise of LV dP/dt during avoidance but contributed proportionally less to the elevations of HR and CO. Inter-individual differences in myocardial reactivity were however completely ascribable to beta-adrenergic factors.

Animals↗

PubMed1994

Field evaluation of thirteen regimens for the control of progressive atrophic rhinitis.

The purpose of the study was to evaluate, under field conditions, the effect of prophylactic programs for the control of progressive atrophic rhinitis (PAR)--recommended in different countries. The investigations were carried out on 280 pregnant sows divided into 14 equal groups and 50 slaughter pigs randomly selected from the litters produced by the sows of each of the groups. Efficacy of all programs was recognized on the basis of comparative evaluation of the average daily gain (ADG), morphometric examination of turbinate bones and computer conchal morphometry (TPR). An increase in ADG was noted in 12 of 13 experimental groups when compared to the control group. Usefulness of the evaluated programs differed significantly. Results of TPR relate only partially to the results of visual morphometry and results of ADG.

Animals↗

PubMed1981

Role of baroreceptor reflexes in the hemodynamic and heart rate responses to althesin, ketamine and thiopentone anesthesia.

The effects of i.v. infusions of althesin, ketamine and thiopentone were studied in instrumental rabbits, in doses that produced similar levels of light anesthesia. The main hemodynamic differences were in the rises in mean arterial pressure (MAP) and in total peripheral resistance (TPR) which were in the order of ketamine greater than thiopentone greater than althesin. These rises in MAP and TPR did not occur in sino-aortic denervated rabbits suggesting that in normal rabbits these depended on the integrity of the arterial baroreceptors and /or chemoreceptors. The heart rate increased with all anesthetics mainly owing to reduction in vagal efferent activity, except with althesin where cardiac sympathetic activity increased also. Baroreceptor--heart rate reflex properties were studied by deriving sigmoid curves relating MAP to heart period (HP, i.e. pulse interval). All drugs depressed the following curve parameters: (i) HP range, i.e. the difference in HP plateaux from maximal tachycardia to maximal bradycardia; and (ii) the reflex gain (sensitivity). The order of depression was ketamine greater than thiopentone greater than althesin, i.e. the same as the order in which they evoked pressor effects. The results suggest that the 3 anesthetics produce differing depression of afferent mechanisms related to baroreceptor reflexes and that this accounts for both the differences in pressor effects (through disinhibition of constrictor tone) and in depression of the vagal and sympathetic components of the baroreceptor--heart rate reflex.

Alfaxalone Alfadolone Mixture↗

PubMed1982

Effects of ketamine and Althesin Anesthesia on baroreceptor--heart rate reflex and hemodynamics of intact and pontine rabbits.

The changes in baroreceptor-heart rate reflex properties and in hemodynamics produced by light ketamine anesthesia were studied in one group of rabbits before and after infracollicular decerebration and those produced by althesin anesthesia in another group. Ketamine produced marked depression of baroreceptor reflex-mediated vagal effects on heart rate which was of similar magnitude in intact and pontine decerebrate rabbits; this indicates that its action was largely at or below the pons. Althesin produced much less vagal depression than ketamine in the intact rabbit but in pontine rabbits the depression was greatly enhanced. The smaller vagal depression in the intact rabbit appears to be due to a facilitatory effect through a suprapontine pathway by Althesin which partially masks its depressant effect below the pons. In the intact rabbit ketamine produced a greater rise in blood pressure than Althesin anesthesia for 1 h; the greater pressor response was due to a transient rise in total peripheral resistance (TPR) and a sustained rise in cardiac output. The difference in the blood pressure responses was mainly due to differences in action of the two anesthetics at or below the pons and only the transient rise in TPR during ketamine anesthesia was mediated through a suprapontine pathway.

Alfaxalone Alfadolone Mixture↗

PubMed1982

Effect of ketamine, althesin, and thiopentone on the Valsalva-constrictor and heart rate reflexes of the rabbit.

The circulatory effects of Valsalva-like manoeuvers were studied before and during i.v. infusions of either ketamine, Althesin and thiopentone given in doses that produced similar levels of light anesthesia. The Valsalva-like manoeuvers were of 30 s duration and consisted of applying Valsalva pressures (VP) from 2.5 to 20 mm Hg to the animal's respiratory valve and to a cuff placed around its thorax and abdomen. In the conscious rabbit the major reflex responses to the Valsalva-like manoeuver were VP-related rises in total peripheral resistance (TPR) and in heart rate which were mainly mediated through intrathoracic baroreceptors and were completely abolished by sino-aortic denervation. Ketamine depressed the Valsalva-TPR response by about 30-40% but Althesin and thiopentone were without effect. Ketamine and thiopentone produced marked depression of the Valsalva-heart rate reflex, but Althesin had relatively little effect. We concluded that ketamine produces greater impairment of blood pressure homeostasis mediated through constrictor and heart rate reflexes evoked through arterial and cardiopulmonary baroreceptors than the other two anesthetics.

Alfaxalone Alfadolone Mixture↗

PubMed1987

The effect of plasma volume expansion on the response to carotid occlusion in the non-human primate.

The purpose of this study was to investigate the effects of plasma volume expansion on the cardiac and peripheral components of the baroreceptor reflex. Nine male Rhesus monkeys were chronically instrumented to measure arterial pressure and aortic blood flow. The aortic arch was denervated at the time of surgery. Bilateral carotid artery occlusion (BCO) was used to elicit the carotid sinus reflex both before and after 25% plasma volume expansion with an iso-osmotic dextran solution. The BCO elicited significant increases in heart rate (HR, 29.8 +/- 5.3 bpm) mean arterial pressure (MAP, 55.0 +/- 8.2 mm Hg) and total peripheral resistance (TPR, 0.076 +/- 0.01 mm Hg/ml/min) coupled with a significant reduction in mean aortic flow (AF, -246.9 +/- 55.3 ml/min) and stroke volume (SV, -2.86 +/- 0.36 ml). Volume expansion significantly attenuated the HR (15.2 +/- 5.8 bpm), MAP (30.4 +/- 4.4 mm Hg) and TPR (0.036 +/- 0.006 mm Hg/ml/min) response to carotid sinus hypotension. The changes in mean AF and SV elicited by BCO, however, were not significantly different between the control and volume expansion conditions. These data suggest that plasma volume expansion significantly attenuates the baroreceptor reflex control of circulation with a similar reduction in both the peripheral resistance and heart rate components of the response.

Anesthesia↗

PubMed1993

Selectivity of boron carriers for boron neutron capture therapy: pharmacological studies with borocaptate sodium, L-boronophenylalanine and boric acid in murine tumors.

Borocaptate sodium (BSH) and L-boronophenylalanine (L-BPA) are two boron carriers used for boron neutron capture therapy (BNCT) in the treatment of glioblastoma and melanoma, respectively. The suitability of these two compounds was evaluated on the basis of pharmacokinetic studies aiming at characterizing their biodistribution, tumor uptake and tumor selectivity. Boric acid was also used as a reference compound since it is nonselective and relatively freely diffusible. The compounds were investigated in two tumor models, a B16 pigmented melanoma and the RIF1 sarcoma. Mice were sacrificed after different boron doses at various post-injection times and tissue and plasma levels measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The proposed minimum effective tumor boron concentration of 15 ppm was achieved in both tumor models for the three compounds tested, although only for L-BPA in the melanoma was this achieved when tumor-plasma ratios were above 1. In the RIF1 model, maximum tumor concentrations of 44 and 31 ppm B were reached after administration of 50 micrograms B/g body weight for boric acid and BSH, respectively. After administration of 12.5 micrograms B/g of L-BPA, maximum concentrations of 15 and 21 ppm were found in the RIF1 and B16 models, respectively. Tumor-plasma ratios (TPR) for BSH remained close to or below unity at all times studied in both tumors. Brain levels of BSH were very low, however, leading to tumor-brain ratios markedly greater than 1 at all times. L-BPA and boric acid showed TPR values above unity in both tumor models, reaching 3.2 in B16.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Hypotensive mechanism of acetyl glyceryl ether phosphorylcholine (AGEPC) in dogs. Effects on hemodynamics and humoral factors.

One-O-hexadecyl-2-O-acetyl-sn-glycero-3-phosphorylcholine (AGEPC) was intravenously administered to anesthetized dogs to study the effects on hemodynamics and several endocrine factors. The effect of AGEPC on local blood flow was also studied by direct intra-arterial injection. Following intravenous injection, blood pressure and cardiac output decreased significantly (p less than 0.001). Changes in total peripheral resistance (TPR) and heart rate were biphasic. TPR increased significantly (p less than 0.01) after an initial slight reduction. Heart rate decreased significantly (p less than 0.01) with only a transient slight elevation. Femoral blood flow was increased (p less than 0.001) by intraarterial injection and decreased (p less than 0.05) by intravenous administration. Plasma norepinephrine (p less than 0.001), epinephrine (p less than 0.01), thromboxane B2 (p less than 0.001), 6-0-PGF1 alpha (p less than 0.01), aldosterone (p less than 0.001) and cortisol (p less than 0.001) were elevated, but plasma renin activity did not change. These results suggest that the hypotensive mechanism of AGEPC is due to both cardiosuppression and vasodilation. AGEPC increased plasma catecholamines, thromboxane A2, PGI2, aldosterone and cortisol which, in turn, may modify hemodynamics.

Aldosterone↗

PubMed1984

Cardiovascular and hormonal responses to bicycle exercise during lower body negative pressure.

UNLABELLED: The purpose was to combine bicycle exercise and LBNP as a model to investigate the mechanisms regulating circulation during gravitational stresses. METHODS: Cardiac Output (CO) by acetylene-, argon-, oxygen rebreathing; Heart Rate (HR) from ECG; Mean Arterial Pressure (MAP) by arm cuff; Plasma Nor-Epinephrine (NE), Epinephrine (E), and Lactate (HLa) by isotope and enzymatic techniques respectively. Total Peripheral Resistance (TPR) = MAP/CO and stroke volume (SV) = CO/HR. Six subjects exercised at 180-200 Watts in the upright position on a mechanically braked computer controlled small bicycle ergometer placed in a LBNP box. The above parameters were measured at rest and at 5 and 9 min of exercise without and with LBNP at -30 or -40 mmHg (depending on LBNP tolerance). RESULTS AND CONCLUSIONS: In the face of an increased sympathetic nervous activity (NE+E,TPR, and HR increased) during exercise in LBNP, there was a decrease in CO and SV indicating that the venous return was insufficient. However, HLa was unchanged demonstrating that the blood flow to the working muscles did not suffer.

Adult↗

PubMed1986

Effect of a proteolytic enzyme inhibitor on the cardiopulmonary response to endotoxin.

Gabexate mesilate (GM), a proteolytic enzyme inhibitor, was given to 31 chronically instrumented sheep either as a pretreatment or treatment to determine its effects on the cardiopulmonary response to endotoxin (ET). Twelve sheep received GM prior to endotoxin (0.75 microgram/kg), 10 after ET and 9 received GM without ET. A typical biphasic response was noted; phase I showed increased lymph flow (QL), reduced lymph to plasma protein ratio (L/P) and increased pulmonary artery pressure (PAP). Phase II occurred two hours after ET; the lymph flow remained elevated and the L/P ratio rose slightly above control. Both phases demonstrated an elevation in total peripheral vascular resistance (TPR) and hematocrit but a reduction in cardiac output (CO). In phase II, QL was reduced 35% with pretreatment; the L/P ratio did not rise as much and the PAP was unchanged. There was also a 35% reduction in lymph flow; no change in the lymph to plasma protein ratio but there was an elevation in pulmonary microvascular pressure. Pretreatment with GM diminished the fall in CO and the rise in TPR seen with endotoxin. The values were unaffected by treatment alone.

Animals↗

PubMed1991

The haemodynamic effect of Bitis nasicornis (rhinoceros horned viper) venom.

1. Intravenous venom (0.0625 mg/kg) in the dog caused an immediate increase in coronary blood flow due to a fall in coronary vascular resistance (CVR). 2. Subsequently, total peripheral resistance (TPR) fell causing a significant reduction in aortic blood pressure (ABP). 3. CVR and TPR returned to normal after 20 min but ABP did not recover completely. 4. The failure of ABP to recover was due to decreased stroke volume and cardiac output (CO). 5. Animals died after four doubling doses of venom following irreversible reductions in CO, ABP and coronary flow.

Animals↗

PubMed1994

Cardiovascular effects of KRN2391, nitroglycerin and cromakalim in dihydroergotamine-treated pithed rats.

1. The effects of KRN2391 on the cardiovascular system were compared with those of nitroglycerin and cromakalim in pithed rats treated with dihydroergotamine (DHE) in order to examine the effects of these drugs on venous blood vessels. 2. DHE (100 micrograms/kg, i.v.) produced increases in mean blood pressure (MBP), cardiac output (CO) and central venous pressure (CVP) without changes in total peripheral vascular resistance (TPR) and heart rate (HR) based on venoconstriction. The DHE-treated pithed rats, nitroglycerin (30 micrograms/kg, i.v.) decreased CO and CVP whereas cromakalim (30 micrograms/kg, i.v.) produced a slight increase in CO followed by a decrease and did not affect CVP. KRN2391 (30 micrograms/kg, i.v.) produced a decrease in CVP without affecting CO. Decreases in MBP and TPR were induced by all drugs. 3. These results suggest that nitroglycerin acts predominantly as a venodilator and KRN2391 and cromakalim showed a venodilating action in addition to an arterial dilating action in DHE treated pithed rats. However, the venodilating action of KRN2391 in this condition is more potent than that of cromakalim.

Animals↗

PubMed1988

Construction of a new shuttle expression vector for Bacillus subtilis and Escherichia coli by using a polycistronic system.

A shuttle vector has been constructed by fusing the Bacillus subtilis trimethoprim-resistance-carrying (TpR) plasmid pNC601 with the Escherichia coli plasmid pBR322. The resultant plasmid pNBL1 can replicate in both B. subtilis and E. coli, conferring Tp resistance on both cells and ampicillin resistance (ApR) on E. coli. The B. subtilis dihydrofolate reductase operon (dfr) on pNC601 and therefore on pNBL1 consists of the thymidylate synthase B gene (thyB) and the TpR-dihydrofolate reductase gene lacking the C-terminal seven codons (designated as drfA' as compared with the complete dfrA gene). A direct-expression vector pNBL3 has been constructed by inserting synthetic oligodeoxynucleotides containing a Bacillus ribosome-binding site (RBS) and the ATG codon downstream from dfrA' on pNBL1. When the E. coli lacZ gene was placed downstream from the dfrA' gene in pNBL3, efficient synthesis of beta-galactosidase was observed in both cells, showing that the polycistronic expression system is suitable for directing expression of heterologous genes. Translational efficiency of the lacZ gene on pNBL3 was further examined in B. subtilis by changing the sequence upstream from lacZ. Unlike the results previously reported [Sprengel et al., Nucleic Acids Res. 13 (1985) 893-909], when RBS was present, the high level of lacZ expression was preserved irrespective of spacing between the stop codon of the upstream dfrA' gene and the start codon of the downstream lacZ gene. However, in the absence of RBS, the spacing between both genes affected lacZ expression. That is, translational coupling of dfrA'-lacZ was observed, although the translational efficiency was very low.

Ampicillin Resistance↗

PubMed1988

Nucleotide sequence of the thymidylate synthase B and dihydrofolate reductase genes contained in one Bacillus subtilis operon.

The nucleotide sequence of the thymidylate synthase B (thyB) and dihydrofolate reductase (dfrA) gene regions from wild-type and trimethoprim-resistant (TpR) mutant strains of Bacillus subtilis 168 was determined. The sequenced region contains two open reading frames, ORF1 and ORF2, which correspond to thyB and dfrA, respectively, and overlap by one nucleotide. The thyB-dfrA genes encode 267 and 168 amino acid polypeptides, respectively, and are present in the order of thyB - dfrA in 5'----3' orientation. This gene order differs from those which have been found in other organisms so far. S1 mapping analysis indicated that both genes were transcribed from a single promoter located upstream from the thyB gene. Thus, the genes belong to an operon. A nucleotide substitution from 'A' in the wild type to 'C' in the TpR mutant was located in the dfrA gene region, with predicted conversion of isoleucine-95 (wild type) to leucine-95 (mutant) in dihydrofolate reductase (DHFR). It is suggested that the affinity between DHFR and Tp is reduced by this alteration.

Amino Acid Sequence↗

PubMed1996

Cloning and sequencing of a gene encoding a new member of the tetratricopeptide protein family from magnetosomes of Magnetospirillum magnetotacticum.

A gene encoding the 22 kDa protein (MAM22) which was localized in the magnetosomes isolated from the magnetotactic bacterium, Magnetospirillum magnetotacticum, was cloned and sequenced. MAM22 was composed of 220 amino acids (aa) with a molecular weight of 24,186 Da. The deduced aa sequence exhibited significant homology with a number of proteins that belong to the tetratricopeptide repeat (TPR) protein family, including mitochondrial protein import receptors and peroxisomal protein import receptors. The presence of three repeats of a degenerate 34-aa consensus sequence, suggest that MAM22 localized in magnetosome membranes may interact with the cytoplasmic proteins containing similar TPR motifs.

Amino Acid Sequence↗

PubMed1995

Isolation of a cDNA encoding a novel human FK506-binding protein homolog containing leucine zipper and tetratricopeptide repeat motifs.

Reduced-stringency PCR was used to isolate a cDNA encoding a novel human FK506-binding protein (FKBP) homolog. The encoded 38-kDa protein (FKBPr38) contains at its N-terminus a domain that is 33% identical to FKBP12. FKBPr38 is a member of a subclass of immunophilins, whose other members include FKBP52 and CyP40 (cyclophilin 40), that contain a three-unit tetratricopeptide repeat (TPR). In addition, FKBPr38 contains a consensus leucine-zipper repeat. The presence of the TPR domain and leucine zipper suggest that FKBPr38 may form homo-multimers or interact with other, as yet unidentified, proteins.

Amino Acid Isomerases↗