RESUMEN
The calcium, magnesium, and cyclic AMP content and 45Ca transport in the aorta and iliac artery and the mechanical properties of these vessels were studied in rats with experimental renal insufficiency. The development of hypertension was attended by an increase in the magnesium content in the vascular wall, a certain decrease in the cyclic AMP level, marked disturbance of 45Ca transport, and changes in the mechanical properties of the vascular wall. The use of dihydrotachysterol or a complex of sex steroids which correct calcium metabolism led to a decrease of arterial hypertension. It is suggested that disorder of calcium metabolism in chronic renal insufficiency plays an essential role in the inadequate regulation of the vascular tone and the development of hypertension.
Asunto(s)
Aorta/metabolismo , Calcio/metabolismo , AMP Cíclico/metabolismo , Hipertensión/metabolismo , Fallo Renal Crónico/metabolismo , Animales , Transporte Biológico , Fenómenos Biomecánicos , Hipertensión/etiología , Fallo Renal Crónico/complicaciones , Magnesio/metabolismo , Masculino , Nefrectomía , Ratas , Resistencia VascularRESUMEN
The present-day notions on the trends and mechanisms of changes in the activity of the cyclic nucleotide system are considered in the age aspect. Their role in disturbances of the neurohumoral regulation processes at the molecular level is discussed. Biochemical mechanisms of changes in the receptor-effector reactions are analyzed. An analysis of these changes is very important for elucidating general regularities of the cyclase system functioning with disturbances of biochemical regulation at the membrane and cell levels.
Asunto(s)
Adenilil Ciclasas/fisiología , Envejecimiento , AMP Cíclico/fisiología , Neurotransmisores/fisiología , Receptores de Superficie Celular/fisiología , Adenilil Ciclasas/metabolismo , Tejido Adiposo/metabolismo , Tejido Adiposo/fisiología , Animales , Células Sanguíneas/metabolismo , Células Sanguíneas/fisiología , Fenómenos Fisiológicos Cardiovasculares , Sistema Cardiovascular/metabolismo , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/fisiología , AMP Cíclico/metabolismo , Humanos , Hígado/metabolismo , Hígado/fisiología , Fluidez de la Membrana , Receptores de Superficie Celular/metabolismoRESUMEN
It is shown that under conditions of experimental limitation of coronary blood flow in rabbits the intensity of radioactive label (32P) incorporation into creatine phosphate lowers essentially. This evidences for inhibition of creatine phosphorylation in mitochondria under ischemia due to a decrease in the activity of a mitochondrial isoenzyme of creatine kinase.
Asunto(s)
Enfermedad Coronaria/metabolismo , Metabolismo Energético , Miocardio/metabolismo , Fosfocreatina/metabolismo , Radioisótopos de Fósforo , Animales , Fosfatos/metabolismo , ConejosRESUMEN
A comparative biochemical study of the structural-functional peculiarities of genetic apparatus and the content of lipid peroxidation products in the liver nuclei and mitochondria of adult (4.5-5.5 months) and old (22-24 months) CBA mice was carried out. The age-related changes were found as follows: relative content of transcriptionally active and matrix-bound chromatin fractions was decreased, and that of transcriptionally low active fraction was increased; the value of protein/DNA was increased only in transcriptionally active fraction; the value of mitochondrial genome expression coefficient was diminished due to a decreased content of proteins encoded by mtDNA; the concentrations of Schiff bases were elevated both in the nuclei and mitochondria. Possible mechanisms of lipid peroxidation involvement in the above mentioned changes of the nuclear and mitochondrial genetic apparatus are discussed.
Asunto(s)
Envejecimiento/genética , Núcleo Celular/genética , Peroxidación de Lípido/fisiología , Mitocondrias Hepáticas/genética , Animales , Cromatina/genética , ADN Mitocondrial/genética , Masculino , Ratones , Ratones Endogámicos CBA , Relación Estructura-ActividadRESUMEN
Evidences are given that implantation of human apo A-I gene to experimental animals induces essential changes in the functional state of hepatocyte plasmatic phospholipid composition, hyperpolarization development, as well as changes in the Na, K-ATPase and adenylate cyclase activities. The presence of generalized cell reaction is evidenced from the fact than biosynthesis of summary proteins gets enhanced during the above changes.
Asunto(s)
Apolipoproteína A-I/genética , Regulación de la Expresión Génica/fisiología , Técnicas de Transferencia de Gen , Hígado/metabolismo , Adenilil Ciclasas/metabolismo , Animales , Membrana Celular/genética , Membrana Celular/metabolismo , Humanos , Liposomas , Lípidos de la Membrana/metabolismo , Proteínas de la Membrana/metabolismo , Ratas , Ratas Wistar , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Factores de TiempoRESUMEN
Content and the ratio of cAMP/cGMP in myocardium, liver tissue and sceletal muscle were similar in adult and old rats. Adrenaline (5 . 10(-6) M) caused more distinct increase in content of cAMP in the old animals. After treatment with NaF (0.01 M) the age differences in the cAMP content were observed only in the heart muscle. Adrenaline appears to activate most effectively adenylate cyclase in tissues of old rats; the enzyme is apparently responsible for enhanced sensitivity to the hormone in senile age.
Asunto(s)
AMP Cíclico/análisis , Epinefrina/farmacología , Hígado/análisis , Músculos/análisis , Miocardio/análisis , Factores de Edad , Animales , GMP Cíclico/análisis , RatasRESUMEN
Age-dependent differences were found in patterns of rat liver adenylate cyclase system in response to hepatectomy-induced proliferation. After hepatectomy a decrease in basic activity of adenylate cyclase and in content of cAMP were observed only in adult animals. At the same time, the epinephrine-stimulated enzymatic activity was decreased in old hepatectomized rats as compared with intact animals. These alterations in regulatory activity of the adenylate cyclase system appear to affect the intensity of DNA biosynthesis and the functional activity of regenerating liver tissue of old rats.
Asunto(s)
Adenilil Ciclasas/metabolismo , Envejecimiento/metabolismo , Hepatectomía , Hígado/enzimología , Animales , AMP Cíclico/metabolismo , RatasRESUMEN
Simulation of myocardial hyperfunction and hypertrophy in rats exhibited the age- and hypertrophy step-dependent alterations in the system of cyclic nucleotides. Significant activation of the HC-cGMP system, decrease in content of cAMP and stimulation of the AC activity were detected in old animals at the emergency step. At the later steps content of cAMP and the AC stimulated activity were increased more distinctly in adult rats as compared with old animals. These alterations were responsible for age-related peculiarities of myocardial contractility at the emergency step as well as for development of hypertrophy at the later steps. The cyclase system appears to facilitate the age-related adaptation of myocardium to overloading during the old age.
Asunto(s)
Envejecimiento/metabolismo , Cardiomiopatía Hipertrófica/metabolismo , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Miocardio/metabolismo , Animales , Coartación Aórtica/complicaciones , Coartación Aórtica/metabolismo , Cardiomiopatía Hipertrófica/etiología , RatasRESUMEN
The denervation-induced changes of cyclic nucleotide concentrations adenylate cyclase activity and resting membrane potential were studied in gastrocnemius muscle of adult and old rats. Under conditions of denervation alterations in resting membrane potential and in adrenaline-stimulated adenylate cyclase activity had a biphasic character in the muscle studied: resting membrane potential was increased and the adenylate cyclase activity was decreased following 30 min denervation, while the opposite effect was observed after 2 weeks denervation. The denervation did not alter cGMP concentration. In old animals more pronounced changes of cAMP level were found in denervated gastrocnemius muscle.
Asunto(s)
Adenilil Ciclasas/metabolismo , Envejecimiento/metabolismo , Desnervación Muscular , Músculos/metabolismo , Nucleótidos Cíclicos/metabolismo , Envejecimiento/fisiología , Animales , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Potenciales de la Membrana , Músculos/enzimología , Músculos/fisiología , RatasRESUMEN
Activity of cAMP phosphodiesterase was similar in leukocytes of healthy persons and of the patients with bronchial asthma in the period of remission. The enzymatic activity was independent on the form of the impairment (infectious-allergic or atopic types). Sensivity of cAMP phosphodiesterase to the effect of its inhibitors and stimulants--theophylline, papaverine and imidazole was higher in the patients as compared with the healthy persons. Prolonged therapy with the phosphodiesterase inhibitors did not lead to development of resistance.
Asunto(s)
Asma/enzimología , AMP Cíclico/sangre , Leucocitos/enzimología , Hidrolasas Diéster Fosfóricas/sangre , Adulto , Activación Enzimática/efectos de los fármacos , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Inhibidores de Fosfodiesterasa/farmacologíaRESUMEN
Studies were made of the effects of various classes of lipoproteins (LP) from the blood of rabbits with experimental hypercholesterolemia and human subjects with pronounced atherosclerosis on the vascular tone of rat thoracic aorta specimens. In hypercholesterolemia, there was a considerable weakening of a vasodilatory action of atherogenic LP fractions--LDL and VLDL. A vasodilatory effect of HDLP was not changed. In subjects suffering from atherosclerosis vasodilatory effects of both atherogenic and antiatherogenic HDLP decreased significantly. The revealed changes were related to shifts in lipid and protein components of LP complexes manifesting in the development of dyslipoproteinemia and dysapoproteinemia. In atherosclerosis accompanied with more profound changes suppression of vasodilatory effects of LP is greater than in transient experimental hypercholesterolemia. Consequently, changes of lipid and apo composition of LP and weakening of their vasodilatory action play a considerable role in the vessel tone changes in atherogenic situation.
Asunto(s)
Apolipoproteínas/farmacología , Arteriosclerosis/sangre , Hipercolesterolemia/sangre , Lipoproteínas/farmacología , Vasoconstrictores/farmacología , Vasodilatadores/farmacología , Anciano , Animales , Aorta Torácica/efectos de los fármacos , Apolipoproteínas/sangre , Modelos Animales de Enfermedad , Humanos , Lipoproteínas/sangre , Persona de Mediana Edad , Conejos , Ratas , Ratas Wistar , Vasoconstrictores/sangre , Vasodilatadores/sangreRESUMEN
The effect of various doses of acetylcholine on the content of myocardial cGMP was studied in rats of different age. The degree of changes was shown to depend on acetylcholine dosage and animals' age. Low doses produced more potent effect in adult rats. It is suggested that these features of alteration of cGMP content may be a reason for increased myocardial sensitivity to acetylcholine in old age.
Asunto(s)
Acetilcolina/farmacología , GMP Cíclico/análisis , Miocardio/análisis , Acetilcolina/administración & dosificación , Acetilcolina/fisiología , Factores de Edad , Animales , Relación Dosis-Respuesta a Droga , Corazón/fisiología , Técnicas In Vitro , Neostigmina/farmacología , Ratas , Receptores Colinérgicos/efectos de los fármacosRESUMEN
A study was made of age peculiarities of the insular function of the pancreas and of the indices of insuline provision of the organism in rat under conditions of sugar loading. It was shown that, in spite of hyperinsulinemia and a higher rate of insuline release glucose release in old rats became worse; this testified to the development of a relative insuline insufficiency in animals of old age. Hyperinsulinemia in old rats coursed against the background of a decreased total blood insular activity and increased "factor of insulin inactivation". The development of a relative insuline insufficiency in old rats depended on both the insular and the non-pancreatic factors, leading to a decrease of the biological activity of insuline.
Asunto(s)
Glucemia/metabolismo , Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Factores de Edad , Animales , Ácidos Grasos no Esterificados/sangre , Secreción de Insulina , Masculino , Ratas , Factores de TiempoRESUMEN
Aqueous solution of L-leucine-14C (specific activity 339 mCi/mmol) was introduced in a dose of 7-8 microliter to the ventral horn (L5,6) of the spinal cord of adult (8-12 month) and old (26-28 month) rats. The radioactivity of various parts of the corresponding ventral roots was measured after 1-2.5 hrs. Labelled substances (including protein) were found to migrate with fast flow in adult rats with the rate of 408 +/- 10.9 and 380 +/- 22 mm/24 hrs, respectively, as compared with 217 +/- 11.3 and 200 +/- 40 mm/24 hrs in old rats. The axoplasmic flow slows down in old rats with the increase of distance from the neuronal body. Uncoupling of oxidation and phosphorylation due to intraperitoneal administration of 2.4-dinitrophenol, NaF inhibition of glycolysis, hypoxic hypoxia produce more marked deceleration of axoplasmatic flow in old rats, while small doses of NaF accelerate the flow, which correlates with the rise of cAMP level in the ventral roots.
Asunto(s)
Envejecimiento , Transporte Axonal , Metabolismo Energético , Neuronas Motoras/fisiología , Médula Espinal/fisiología , Animales , Glucólisis , Masculino , Fosforilación Oxidativa , Consumo de Oxígeno , Ratas , Factores de TiempoRESUMEN
The lipid peroxidation (LPO) level between in the adult and old rats brain and liver was determined as to be essentially undiffering. Stress activated the LPO independence the age of animals and tissues investigated. The concentration changes of LPO products testify to it. In the adult rats under the stress capability of tissues to induction in vitro ferment and ascorbat-depending LPO, in comparison with the control, decreases, at old--does not change in the brain and considerably grows in the liver. Stress is accompanied by an oppression of Na, K-ATP-ase PM activity of hepatocytes, more expressed in the old animals.
Asunto(s)
Envejecimiento/metabolismo , Encéfalo/metabolismo , Peroxidación de Lípido , Estrés Fisiológico/metabolismo , Animales , Masculino , Ratas , Ratas WistarRESUMEN
To study the age-related relationship between the membrane status and activity of membrane-linked enzymes, the physicochemical properties of plasma membranes and activity of transfer ATPase and adenylate cyclase were assessed in tissues of rats of different ages. The lipid matrix of membranes was found to undergo appropriate changes with age. The most significant shifts are manifested under functional and metabolic stresses. It has been demonstrated that the shifts in the regulated activity of the studied enzymes are induced by changes in membrane interactions. The findings suggest predominantly the membrane mechanisms that determine the insufficiency of adaptation mechanisms in old age.
Asunto(s)
Membrana Celular/análisis , Lípidos/análisis , Adaptación Fisiológica , Adenosina Trifosfatasas/análisis , Adenilil Ciclasas/análisis , Factores de Edad , Animales , Química Encefálica , Colesterol/análisis , Hepatectomía , Hígado/análisis , Miocardio/análisis , Fosfolípidos/análisis , RatasRESUMEN
The results obtained show the essential changes in functional state of hepatocyte's plasmatic membrane due to the implantation of human ApoA1 gene to the rat liver. The changes in phospholipid composition, hyperpolarization, increase in activity of membrane bound enzymes, cytochrome P-450 and biosynthesis of liver total proteins have been found. The essential changes characterizing cell effect were more marked in the adult rats, and membrane effect in the old ones.