ABSTRACT
PURPOSE: N-Acetyl-ß-D-hexosaminidase (HEX) is an exoglycosidase which has been extensively studied and which has been used as a marker for inflammation. It was therefore thought that measurement of the activity of this enzyme might be useful in diagnosing gestational diabetes mellitus (GDM) as this condition is frequently associated with inflammation. The main object of the study was the determination of N-acetyl-ß-D-hexosaminidase activity in women with GDM and 3 months postpartum in comparison with control groups of non-pregnant and healthy pregnant women. MATERIAL AND METHODS: Twenty-five blood serum samples from women with GDM and women 3 months postpartum; 20 blood serum samples from non-pregnant and healthy pregnant women (control groups) were enrolled into the study. Serum was prepared from all blood samples and HEX activity was measured by the method of Chateriee et al. (modified by Zwierz et al). RESULTS: A statistically significantly increase in the activity of HEX in the GDM blood serum was found as compared to the control groups (p<0.05). Further analysis showed a statistically significant decrease in the activity of HEX among postpartum women, but the level of enzyme activity was still above the normal control level in comparison to the control group of nonpregnant healthy women (p<0.05). CONCLUSIONS: Changes in the activity of HEX appear to be involved in the pathogenesis of gestational diabetes mellitus. Determination of HEX activity may have prognostic significance as an early indicator of diabetes mellitus among GDM women in the future.
Subject(s)
Diabetes, Gestational/blood , beta-N-Acetylhexosaminidases/blood , Adult , Biomarkers/blood , Diabetes, Gestational/diagnosis , Diabetes, Gestational/immunology , Female , Humans , Postpartum Period/blood , Pregnancy , Pregnancy Trimester, Second/blood , Pregnancy Trimester, Third/blood , Retrospective Studies , Young AdultABSTRACT
PURPOSE: The influence of the selective antagonism of metabotropic glutamate receptor subtype 5 (mGluR5) by MPEP (2-methyl-6-(phenylethynyl)-pyridine) on some behaviors was tested in control groups of rats and in rats exposed to short-term hypoxia once or to repeated episodes of hypoxia. MATERIAL AND METHODS: We used the following methods: the open field test, the passive avoidance test and the object recognition test. Experimental hypoxia was produced by placing rats in a glass chamber flushed with a mixture of 2% O2 in N2. RESULTS: MPEP applied intravenously (IV) at the dose of 1 mg kg-1 significantly enhanced locomotor and exploratory activity, impaired acquisition, but improved consolidation and retrieval in the passive avoidance situation and did not alter rats' activity in the object recognition test. The single short-term hypoxia significantly inhibited motility of rats and profoundly impaired acquisition, consolidation and retrieval processes, but the positive effect of MPEP on retrieval was preserved. Hypoxia also did not influence the activity of rats in the object recognition object. The repeated episodes of short-term hypoxia were induced for five consecutive days and it also inhibited motility of rats, but did not change consolidation and retrieval processes. The episodes of hypoxia significantly diminished the beneficial effect of MPEP on consolidation and retrieval, and also the enhancement of locomotor and exploratory activity. MPEP, used in rats subjected to the single or the repeated episodes of short-term hypoxia, did not change recognition memory. CONCLUSION: MPEP used before the single episode of hypoxia only, had beneficial effect on retrieval.
Subject(s)
Behavior, Animal/drug effects , Excitatory Amino Acid Antagonists/therapeutic use , Hypoxia/drug therapy , Pyridines/therapeutic use , Receptors, Metabotropic Glutamate/antagonists & inhibitors , Animals , Avoidance Learning/drug effects , Excitatory Amino Acid Antagonists/administration & dosage , Exploratory Behavior/drug effects , Hypoxia/psychology , Injections, Intravenous , Locomotion/drug effects , Male , Memory/drug effects , Pyridines/administration & dosage , Rats , Rats, Wistar , Reaction Time/drug effects , Receptor, Metabotropic Glutamate 5 , Recognition, Psychology/drug effects , Time FactorsABSTRACT
PURPOSE: This study examines possible interactions between behavioral effects and mGluR1 (class I metabotropic glutamate receptor) by injecting AIDA [(RS)-1-aminoindan-1,5-dicarboxylic acid] in rats with experimental chronic hyperammonemia (chHA). MATERIAL/METHODS: The effects of mGluR1 antagonist on some behaviors were tested in control groups of rats and in rats with chHA. Experimental chHA was induced by intraperitoneal injection of ammonium acetate (12 mmol/kg) for five consecutive days. We used the following behavioural tests: the open field test, the passive avoidance test and the elevated "plus" maze. RESULTS: In control rats AIDA administered intracerebroventricularly (i.c.v.) at the dose 100 nmol decreased the number of crossings and bar approaches in the open field test and impaired acquisition and recall in the passive avoidance situation. ChHA significantly inhibited locomotor and exploratory activity and profoundly impaired acquisition and recall processes in the passive avoidance test and significantly increased acute stress responses. AIDA increased locomotor activity in chHA rats (especially number of crossed fields and rearings) and produced anxiety enhancement in rats with chHA. AIDA used in rats with chHA significantly improved acquisition and retrieval processes. CONCLUSIONS: The obtained results suggest that AIDA, the antagonist of mGluR1, had beneficial effects on learning and memory in rats with experimental chronic hyperammonemia.
Subject(s)
Behavior, Animal/drug effects , Excitatory Amino Acid Antagonists/therapeutic use , Hyperammonemia/drug therapy , Indans/therapeutic use , Receptors, Metabotropic Glutamate/antagonists & inhibitors , Acetates/adverse effects , Animals , Anxiety/psychology , Avoidance Learning/drug effects , Chronic Disease , Exploratory Behavior/drug effects , Hyperammonemia/psychology , Injections, Intraperitoneal , Injections, Intraventricular , Locomotion/drug effects , Male , Maze Learning/drug effects , Mental Recall/drug effects , Random Allocation , Rats , Rats, Wistar , Stress, Psychological/psychologyABSTRACT
The study was designed to investigate the effects of NMDA receptor agonist on the behavioral activity in rats with experimental hyperammonemia. The experiments were performed on adult male Wistar rats. Experimental hyperammonemia was induced by intraperitoneal injections of tioacetamide (TAA, 200 mg/kg) for three consecutive days. Rats treated with saline (0.9%) served as control. Stimulation of the NMDA glutamatergic receptor was evoked by ip. injection of agonist N-methyl-D-aspartate acid (NMDA) in a dose of 30 mg/kg thirty minutes before experiments. Memory motivated affectively was evaluated in the passive avoidance responses. The speculative influence of the treatment on anxiety and motor activity was tested in elevated plus-maze and in open field respectively. To show change of NMDA receptor function after various doses of agonist, the seizures evoked by N-methyl-D-aspartate acid was carried out. This experiment showed that with rise of dose of NMDA time to appear of convulsions was contracted in rats with hyperammonemia as well as in control rats. Dose of NMDA caused convulsions was three times as less in rats with hyperammonemia than dose in control. Time of duration of convulsions was proportional to applied dose of NMDA and it lengthened with rise of agonist's dose in both groups of studied animals. Furthermore, we observed that NMDA increased motor activity of control rats in open field test, but not in rats with hyperammonemia (treated tioacetamide). Hyperammonemia did not have significant influence on motor activity and on a passive avoidance latency. The NMDA given in control and in hyperammonemia, increased acquisition, consolidation and recall of a passive avoidance responses. Moreover, NMDA had anxiogenic-like profile in elevated plus-maze. In rats with hyperammonemia NMDA had no influence on locomotor activity but it significantly increased memory in a passive avoidance responses. Furthermore, we observed that reactivity of NMDA glutamate receptor in rats with hyperammonemia was higher than in control rats.
Subject(s)
Behavior, Animal/drug effects , Excitatory Amino Acid Agonists/pharmacology , Hyperammonemia/psychology , Liver Failure/complications , N-Methylaspartate/pharmacology , Receptors, Glutamate/drug effects , Animals , Avoidance Learning/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Exploratory Behavior/drug effects , Hyperammonemia/etiology , Male , Maze Learning/drug effects , Motor Activity/drug effects , N-Methylaspartate/adverse effects , Rats , Rats, Wistar , Receptors, Glutamate/metabolism , Seizures/chemically inducedABSTRACT
We investigated the effects of 2R,4R-APDC, a selective group II metabotropic glutamate receptor (II mGluR) agonist, on certain behaviors in rats subjected and non-subjected to hypoxia. Short-term hypoxia was used as a model of experimentally induced amnesia. 2R,4R-APDC given intracerebroventricularly (icv) at doses of 1 mumol and 100 nmol decreased the number of crossings and rearings in the open field, impaired acquisition and consolidation but improved retrieval in the passive avoidance tests. It also shortened the time spent in open arms and prolonged the time spent in closed arms, reduced the number of open and closed arms entries in an elevated "plus" maze, which is a measure of anxiety. Four-minute hypoxia (2% O(2), 98% N(2)) retrieval of conditioned responses, and exhibited an anxiogenic effect in the elevated "plus" maze in rats, i.e. it reduced the time spent in open arms and the number of entries to closed and open arms. 2R,4R-APDC effect on locomotor and exploratory activity was not changed after hypoxia, i.e. we observed inhibition of motility. This agonist of II mGluRs used at both doses before hypoxia significantly improved acquisition and retrieval, and had dual effect on consolidation, viz. at a dose of 1 mumol, it impaired this process and at a dose of 100 nmol it improved it. In the elevated "plus" maze, rats pretreated with 2R,4R-APDC and then subjected to hypoxia shortened the time spent in open arms and prolonged the time spent in closed arms, reduced the time spent in open arms, i.e. the drug exhibited anxiogenic effect. We conclude, therefore, that 2R,4R-APDC itself impaired acquisition and consolidation, enhanced retrieval but in rats undergoing hypoxia, it improved acquisition, retrieval and when used at the dose of 100 nmol enhanced consolidation. 2R,4R-APDC had beneficial effect in hypoxia-induced memory impairment in passive avoidance test.
Subject(s)
Avoidance Learning/drug effects , Hypoxia, Brain/drug therapy , Proline/analogs & derivatives , Proline/pharmacology , Proline/therapeutic use , Animals , Avoidance Learning/physiology , Hypoxia, Brain/physiopathology , Male , Memory/drug effects , Memory/physiology , Rats , Rats, WistarABSTRACT
The aim of our study was to estimate the involvement of the peripheral N-methyl-D-aspartate receptors in regulation of cardiovascular function. For this purpose we examined the effects of intravenous injection of the agonists - NMDA (0.025; 0.05 and 1.0 mg/kg iv) and 1R-3R-ACPD (0.025; 0.05 and 1.0 mg/kg iv) - and antagonist of NMDA receptors DL-AP7 (0.02; 0.07 and 0.2 mg/kg iv). To determine if the effects of NMDA come from central or peripheral action we observed the effect during blockade of autonomic ganglion by using the nicotinic receptor antagonist - chlorisondamine (1.25 mg/kg iv). Administration of NMDA in three doses evoked slight hypotension after injection of the medium dose, 0.05 mg/kg. In the condition of pretreatment with 1.25 mg/kg chlorisondamine the hypotensive effect of NMDA was markedly reduced, what might suggest that NMDA-induced hypotension raised from the action within the brain. The competetive NMDA receptor antagonist DL-AP7 slightly increased the blood pressure. None of the injected drug had an influence on the heart rate in our in vivo study. It is concluded that the peripherally localized NMDA receptors may take a part in regulation of cardiovascular system, since their stimulation or blockade evoked the changes of systemic pressure.
Subject(s)
2-Amino-5-phosphonovalerate/analogs & derivatives , Cardiovascular Physiological Phenomena , Receptors, N-Methyl-D-Aspartate/physiology , 2-Amino-5-phosphonovalerate/pharmacology , Animals , Blood Pressure/drug effects , Blood Pressure/physiology , Chlorisondamine/pharmacology , Cycloleucine/analogs & derivatives , Cycloleucine/pharmacology , Dose-Response Relationship, Drug , Heart Rate/drug effects , Heart Rate/physiology , Injections, Intravenous , Male , N-Methylaspartate/agonists , N-Methylaspartate/pharmacology , Rats , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/agonists , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitorsABSTRACT
The permeability in the intact and diabetic rat coronary circulation after administration of secretin (3.0 micromol/kg i.v.), an inhibitor of NOS (nitric oxide synthase), and L-NAME (N(G)-nitro-L-arginine-methyl ester hydrochloride) (1 mg/kg i.v.), and both substances given together, were studied. To measure protein extravasation Evans blue dye was used as a marker of vascular permeability. The vascular permeability of the left ventricle did not differ in intact and diabetic rats. In the diabetes state increased permeability of atria was observed. Administration of secretin did not influence the coronary vascular permeability in either the intact or the diabetic rats. L-NAME increased the atria permeability and did not change left ventricle permeability. In diabetes, injection of L-NAME caused a decrease in the permeability in both the atria and left ventricle. In intact rats secretin diminished the L-NAME effect in the atria. In diabetic rats co-administration of secretin+L-NAME increased the permeability of the atria and left ventricle, but L-NAME administered alone decreased them. Secretin modified the effect of L-NAME on coronary permeability in intact and diabetic rats.
Subject(s)
Capillary Permeability/drug effects , Coronary Circulation/drug effects , Diabetes Mellitus, Experimental/blood , NG-Nitroarginine Methyl Ester/pharmacology , Secretin/pharmacology , Animals , Diabetes Mellitus, Experimental/metabolism , Drug Interactions , Evans Blue , Heart Atria/drug effects , Heart Ventricles/drug effects , Male , NG-Nitroarginine Methyl Ester/administration & dosage , Nitric Oxide/metabolism , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Rats , Rats, Wistar , Secretin/administration & dosage , Ventricular FunctionABSTRACT
The influence of secretin (10(-10) - 10(-8) M), a gastrointestinal hormone, on the relaxing response of rat thoracic aorta rings preconstricted by 40 mM KCl was studied by measuring changes in isometric tension in intact and diabetic animals. Initial contraction of aorta rings was markedly decreased in diabetic state. Secretin administered at two higher doses (10(-9), 10(-8) M) caused significant relaxation. In diabetes, relaxing effect was observed at all three doses of the peptide. These data indicate that secretin relaxes thoracic aorta rings and state of diabetes markedly amplifies the relaxant response to this peptide.
Subject(s)
Diabetes Mellitus, Experimental/physiopathology , Secretin/pharmacology , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiopathology , In Vitro Techniques , Isometric Contraction/drug effects , Male , Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Muscle, Smooth, Vascular/drug effects , Potassium Chloride/pharmacology , Rats , Rats, WistarABSTRACT
The present study aimed to determine the influence of nitric oxide (NO) on the action of secretin in the cardiovascular system in intact rats. The studies involved the in vivo measurements of the systolic (SBP) and diastolic (DBP) blood pressure. The measurements were conducted when NO was absent, which was attained by the use of NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), and when NO was in excess which was obtained by the administration of L-arginine (L-arg), the substrate for NO synthase or exogenous donor of NO, sodium nitroprusside (SNP). Secretin given at the following three doses: 0.75, 1.5 and 3.0 micromoles/kg iv increased SBP and DBP. L-NAME inhibited the slight hypertensive effect of secretin. L-arg abolished the hypertensive effect of the peptide given at the smallest dose, did not change the effect of secretin administered at the medium dose (which did not raise the pressure) and preserved the action of the highest secretin dose. SNP abolished the hypertensive effect of all doses of the peptide. In conclusion, the study has shown that both the lack and excess of NO change the in vivo effect of secretin in intact rats.
Subject(s)
Blood Pressure/drug effects , Hemodynamics/drug effects , Nitric Oxide/pharmacology , Secretin/metabolism , Animals , Enzyme Inhibitors/pharmacology , Heart Rate/drug effects , Male , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Rats , Rats, WistarABSTRACT
The present study was designed to examine the effect of absence or excess of NO on secretin-mediated responses in the isolated heart. This problem was investigated using the modified Langendorff's method. Secretin administered at two higher doses increased the cardiac contraction amplitude (p < 0.05), but did not change the heart rate and coronary outflow. NO was depleted from experimental system by perfusion of the isolated heart with NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) at 10 microM. It caused a significant decrease in coronary outflow (p < 0.01) and the tendency to bradycardia (p > 0.05) with no change in cardiac contraction amplitude. L-NAME abolished the positive inotropic effect of the medium secretin dose and preserved the inotropic effect of the highest dose of the peptide. It reversed the tendency to decrease coronary outflow induced by secretin (and L-NAME) given separately. To study the effect of NO excess, we applied the substrate for NO synthesis, amino acid L-arginine (L-arg) (100 microM) or exogenous donor of NO--sodium nitroprusside (SNP) (100 microM). Both substances did not affect the isolated heart function. L-arg did not change the effect of secretin, however it abolished non significant decrease in coronary outflow evoked by the highest dose of secretin. SNP preserved the positive inotropic action of the peptide and expressively reversed the negative values of coronary outflow observed after its co-administration with the highest dose of secretin. These results indicate that both the absence and excess of NO change the cardiac effect of secretin in the same direction.
Subject(s)
Heart/drug effects , Hemodynamics/drug effects , Nitric Oxide/pharmacology , Secretin/pharmacology , Animals , Blood Pressure/drug effects , Enzyme Inhibitors/pharmacology , In Vitro Techniques , Male , Myocardial Contraction/drug effects , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitroprusside/pharmacology , Rats , Rats, WistarABSTRACT
The present study was aimed to determine the cardiovascular effects of secretin in healthy rats and rats with streptozotocin-induced diabetes mellitus. In vivo studies involved measurements of the systolic and diastolic blood pressure, and heart rate of rats given secretin at the following doses: 0.75; 1.5; 3.0 mumol/kg. In vitro, the isolated heart function was studied according to the modification of Langendorff's method. The cardiac contraction amplitude, heart rate and coronary outflow were measured while secretin was given at the following three doses: 110.0; 485.2; 1100.0 nmol/0.1 ml. The results were compared with effects of secretin in diabetic rats. In vivo, secretin slightly increased systolic and diastolic blood pressure. Diabetes abolished hypertensive effect of the peptide, while the highest dose slightly increased heart rate. Secretin given at two higher doses in vitro increased the amplitude, but did not change the heart rate and coronary outflow. In diabetes, the secretin influence on the amplitude was preserved, the drug did not change the heart rate and at two higher doses increased the coronary outflow. In conclusion, the study has shown that diabetic state changes the cardiovascular effects of secretin.
Subject(s)
Cardiovascular Physiological Phenomena/drug effects , Diabetes Mellitus, Experimental/physiopathology , Secretin/pharmacology , Animals , Blood Pressure/drug effects , Coronary Circulation/drug effects , Heart Rate/drug effects , Male , Myocardial Contraction/drug effects , Rats , Rats, Wistar , Secretin/adverse effects , StreptozocinABSTRACT
This study investigated the interaction of cholecystokinin (CCK-33) and its fragments: C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4) with alpha- and beta-adrenoceptor agonists and antagonists. The effects of this interaction on arterial blood pressure and function of isolated heart were studied in rats with 1-month diabetes mellitus (DM) induced by 1-month administration of streptozocin (STZ). We used CCK-33, CCK-8 and CCK-4 in an equimolar dose of 425.0 pmoles/kg i.v. in in vivo, and 42.5 pmoles/0.1 ml in in vitro experiments. We found that 1) DM diminished the hypertensive effect of noradrenaline (NA) and the hypotensive effects of isoprenaline (ISO), phentolamine (PHENT) and propranolol (PROP). CCK-4 and CCK-8 enhanced but CCK-33 did not change a weaker hypertensive effect of NA while all peptides showed the hypotensive effect of PHENT and did not change the hypotensive effect of ISO and PROP. 2) The influence of NA and PROP on isolated heart of diabetic rats remained unchanged after administration of the peptides but that of ISO and PHENT was diminished. CCK-4 enhanced the effects of NA and PHENT, and diminished the influence of ISO and PROP on isolated heart of diabetic rats. CCK-33 enhanced the cardiac effects of NA, ISO and PROP and did not alter PHENT action. CCK-8 did not change the influence of the studied adrenoceptor agonists and antagonists on isolated heart of diabetic rats. The results of the present study demonstrated that the smallest fragment of CCK-33 (CCK-4) modified the influence of alpha- and beta-adrenoceptor agonists and antagonists on cardiovascular system and altered the direction of disturbances caused by DM. The other peptides (CCK-33, CCK-8) interacted with these receptors to a lesser degree in diabetic subjects.
Subject(s)
Adrenergic Agents/pharmacology , Cardiovascular System/drug effects , Cholecystokinin/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Sincalide/pharmacology , Tetragastrin/pharmacology , Adrenergic alpha-Agonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Agonists/pharmacology , Animals , Blood Pressure/drug effects , Diabetes Mellitus, Experimental/chemically induced , Disease Models, Animal , Drug Interactions , Heart/drug effects , Heart/physiology , Heart Rate/drug effects , Isoproterenol/pharmacology , Male , Norepinephrine/pharmacology , Phentolamine/pharmacology , Propranolol/pharmacology , Rats , Rats, Wistar , StreptozocinABSTRACT
The goal of the present study was to examine the interaction of cholecystokinin (CCK-33) and its fragments: C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4) with alpha- and beta-adrenoceptor agonists and antagonists. The effect of this interaction on arterial blood pressure and function of isolated heart was studied in rats. The results indicate that: 1) CCK-33 enhances the influence of catecholamines: noradrenaline and isoprenaline, mainly on the function of isolated heart. This peptide does not change cardiovascular effects of alpha-adrenoceptor antagonist--phentolamine. CCK-33 diminishes the influence of propranolol on the function of isolated heart. The hypotensive effect of beta-adrenoceptor antagonist is not affected by CCK-33. 2) CCK-8 does not alter cardiovascular effects of noradrenaline and isoprenaline. The peptide diminishes the hypotensive effect of phentolamine and reverses the hypotensive effect of propranolol. CCK-8 enhances the influence of propranolol and does not change the influence of phentolamine on the function of isolated heart. CCK-8 enhances bradycardia evoked by propranolol. 3) CCK-4 does not change the influence of noradrenaline and isoprenaline on arterial blood pressure and diminishes the hypotensive effect of phentolamine and propranolol. The peptide does not change cardiac effects of noradrenaline and diminishes the effects of isoprenaline, phentolamine and propranolol. On the basis of the present study, we concluded that CCK-33 and its fragments CCK-8 and CCK-4 modify the cardiovascular action of alpha- and beta-adrenoceptor agonists and antagonists. We suggest that effects we have observed correlate with the activation of the CCK-A receptors (CCK-33, CCK-8) or CCK-B receptors (CCK-4). CCK-related peptides may increase or reduce the effects of catecholamines indirectly through activation of alpha-adrenoceptors. We can not exclude direct action of the peptides on the heart.
Subject(s)
Adrenergic Agents/pharmacology , Cardiovascular System/drug effects , Cholecystokinin/pharmacology , Sincalide/pharmacology , Tetragastrin/pharmacology , Adrenergic alpha-Agonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Blood Pressure/drug effects , Drug Interactions , Heart/drug effects , Heart/physiology , Heart Rate/drug effects , In Vitro Techniques , Isoproterenol/pharmacology , Male , Norepinephrine/pharmacology , Phentolamine/pharmacology , Propranolol/pharmacology , Rats , Rats, WistarABSTRACT
UNLABELLED: The aim of the present study was determinate the role of nitric oxide (NO) in the action of CCK on arterial blood pressure and function of isolated rat heart. Intravenous administration of NO synthase (NOS) inhibitor-NG-nitro-L-arginine methyl ester (L-NAME-100.0 micrograms/kg) increased arterial blood pressure and abolished the hypertensive effect of CCK (administered in the highest dose: 425.0 pmoles/kg i.v.). Donors NO: L-arginine (L-Arg-100.0 mg/kg i.v.) and sodium nitroprusside (SNP-10.0 micrograms/kg i.v.) decreased arterial blood pressure, the hypotensive effect evoked by SNP was greater than produced by L-Arg. CCK administered with L-Arg evoked hypotension (opposite to the hypertensive effect evoked by CCK). When we used CCK at the higher doses (212.5; 425 pmoles/kg i.v.) simultaneously with L-Arg the hypotensive effect was greater than the hypotensive action evoked by L-Arg alone. Administration of CCK with SNP produced the hypotension (similar as after used SNP and opposite to the hypertensive action of the peptide). CCK (21.25, 42.5, 106.25 pmoles/0.1 ml) increased the cardiac contraction amplitude, the peptide injected in lower doses decreased coronary outflow. CCK had no effect on heart rate. L-NAME (10(-5) M) decreased coronary outflow, tendent to evoke bradycardia (p > 0.05) and the compound did not change the cardiac contraction amplitude of isolated heart. L-NAME abolished the influence of CCK on the function of isolated heart. L-Arg (10(-2) M) did not affect function of isolated heart. L-Arg abolished and when we used with CCK in the highest dose reversed the positive inotropic effect of the peptide and tendent to abolish a lowered coronary outflow evoked by CCK. SNP (10(-4) M) decreased the cardiac contraction amplitude. SNP diminished the positive inotropic effect of CCK and did not change other parameters of isolated heart. CONCLUSION: NO does not play a role in cardiovascular action of CCK directly, however inhibitor of NO synthase and donors of NO change the influence of the peptide, mainly on the heart. We suggest that the effect is indirectly through catecholamines.
Subject(s)
Cardiovascular Physiological Phenomena/drug effects , Cholecystokinin/pharmacology , Nitric Oxide/biosynthesis , Analysis of Variance , Animals , Blood Pressure/drug effects , Catecholamines/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Interactions , Enzyme Inhibitors/pharmacology , Male , Myocardial Contraction/drug effects , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Rats , Rats, Wistar , Reference ValuesABSTRACT
Effects of cholecystokinin (CCK-33), caerulein (CER) and pentagastrin (PG) on arterial blood pressure and plasma renin activity (PRA) were studied in rats. The results showed that CCK-33 (106.25, 212.5 and 425.0 pmoles/kg i.v.) increased systolic and diastolic blood pressure and decreased PRA. CER used at doses: 0.37, 1.85 and 3.7 nmoles/kg (i.v.) did not change systolic blood pressure. CER administered at the higher doses slightly decreased diastolic blood pressure, evoked bradycardia and increased PRA. PG used at doses of 0.13, 1.3 and 13.0 nmoles/kg (i.v.) and the peptide given at the highest dose (13.0 nmoles/kg, i.v.) slightly increased arterial blood pressure. PG administered at all doses did not change PRA. This research shows that in spite of similarity in biochemical structure of CCK-33, CER, PG there are differences in effects of the studied peptides on arterial blood pressure and PRA. The correlation between an influence of CCK-33, CER and PG on arterial blood pressure and PRA was also observed.
Subject(s)
Blood Pressure/drug effects , Ceruletide/pharmacology , Cholecystokinin/pharmacology , Pentagastrin/pharmacology , Renin/blood , Animals , Ceruletide/physiology , Cholecystokinin/physiology , Heart Rate/drug effects , Male , Rats , Rats, WistarABSTRACT
The interaction of C-terminal cholecystokinin octapeptide (CCK-8) with beta-adrenoceptors agonist (isoprenaline-ISO) and antagonist (propranolol) and their influence on arterial blood pressure and function of isolated heart in rats with streptozotocin-induced diabetes mellitus (DM) was studied. After blockade of beta-adrenoceptors with propranolol, the hypertensive effect of CCK-8 was observed in the control group but not in DM-group, whereas CCK-8 had no effect on arterial blood pressure in the both studied groups. Stimulation of beta-adrenoceptors with ISO exerted the hypotensive effect of CCK-8 similar as after administration of the amine alone in the control and diabetic rats. CCK-8 increased the cardiac contraction amplitude and had no effect on heart rate and coronary outflow in control hearts. The positive inotropic effect of the peptide was abolished in DM-group. After blockade of beta-adrenoceptors, CCK-8 decreased all studied parameters of isolated hearts, the effect was similar as after infusion of propranolol alone. In DM group, after blockade of beta-adrenoceptors CCK-8 evoked decrease in the cardiac contraction amplitude (as during infusion of propranolol) and heart rate (the effect was greater than that after beta-adrenoceptors antagonist). CCK-8 administrated with ISO increased amplitude, heart rate and decreased coronary outflow of isolated control heart as after administration of ISO alone: in DM-group only the positive inotropic effect was observed. DM modified the effect of CCK-8 in circulatory system of rats. CCK-8 evoked bradycardia independent of stimulation or blockade of beta-adrenoceptors, mainly in DM.
Subject(s)
Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Diabetes Mellitus, Experimental/metabolism , Hemodynamics/drug effects , Sincalide/pharmacology , Animals , Blood Pressure/drug effects , Coronary Circulation/drug effects , Drug Interactions , Heart Rate/drug effects , In Vitro Techniques , Isoproterenol/pharmacology , Male , Myocardial Contraction/drug effects , Propranolol/pharmacology , Rats , Rats, WistarABSTRACT
The effect of cholecystokinin (CCK-33) and its fragments, CCK-8 and CCK-4, on arterial blood pressure and the function of isolated rat heart and catecholamine levels in plasma and from isolated heart tissue in diabetes mellitus were studied. The results indicated that, in diabetes, cardiovascular effects of CCK-33 and CCK-8 are diminished or abolished. Diabetes can change the response of the alpha- and beta-adrenergic system to CCK-33 and CCK-8 and the contents of catecholamines in heart tissue.
Subject(s)
Cholecystokinin/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Heart/drug effects , Hemodynamics/drug effects , Sincalide/analogs & derivatives , Animals , Epinephrine/metabolism , Myocardium/metabolism , Norepinephrine/metabolism , Rats , Sincalide/pharmacologyABSTRACT
1. The effects of cholecystokinin (CCK-33) and its fragments CCK-8 and CCK-4 on arterial blood pressure and the function of isolated rat heart and the amount of catecholamines in plasma, heart tissue were studied. 2. The results indicated that shortening of CCK to CCK-8 and CCK-4 eliminates the circulatory effect of this peptide. 3. A correlation was found between the results of in vivo and in vitro experiments and the amount of catecholamines.
Subject(s)
Blood Pressure/drug effects , Cholecystokinin/pharmacology , Heart Rate/drug effects , Sincalide/pharmacology , Tetragastrin/pharmacology , Animals , Carotid Artery, Common/drug effects , Catecholamines/biosynthesis , In Vitro Techniques , Male , Myocardial Reperfusion , Rats , Rats, WistarABSTRACT
1. The effect of C-terminal fragment of ANF-ANF(24-28)OH on the cardiovascular system was investigated in rats. 2. In vivo this pentapeptide caused the fall of systolic and diastolic blood pressure. 3. ANF(24-28)OH increased cardiac contraction amplitude and changed coronary outflow in vitro. 4. These experiments showed that the shorter fragment of ANF containing five amino acids: Asn24-Ser25-Phe26-Arg27-Tyr28-COOH is a bioactive substance.
Subject(s)
Atrial Natriuretic Factor/pharmacology , Hemodynamics/drug effects , Peptide Fragments/pharmacology , Amino Acid Sequence , Animals , Blood Pressure/drug effects , Heart Rate/drug effects , Male , Molecular Sequence Data , Myocardial Contraction/drug effects , Rats , Rats, WistarABSTRACT
1. The interaction of ANF and ANF(24-28)OH with the agonist, Isoprenaline (ISO), and the antagonist, Propranolol (PRO), of beta-adrenergic receptor in the cardiovascular system in rat was investigated. 2. The studies showed that ANF and C-terminal fragment of ANF, ANF(24-28)OH, interfered with beta-adrenergic receptor. 3. This does not exclude the action of this pentapeptide on the other receptors.
