Search

A comparative study of the generation of hydroxyl radicals (OH*) in the hypertrophic myocardium of SHR-SP rats (n = 8) and in the myocardium of WKY (n = 5) and Wistar (n = 12) rats was performed using the microdialysis technique. The experiments were carried out on anesthetized open-chest male rats (ketamine intraperitoneally, 10 mg/kg) with artificial ventilation. The amount of OH* produced was estimated by high-performance liquid chromatography with electrochemical detection using as a marker 2,3-dihydroxybenzoic acid (2,3-DHBA), a product of the reaction of the hydroxyl radical with salicylic acid added to the perfusate. The quantity of 2,3-DHBA in the dialysate was estimated by the external standard method and expressed in percent of the 2,3-DHBA concentration in the perfusion fluid. The mean baseline value of 2,3-DHBA in dialysate samples in SHR-SP rats (157 +/- 22%, n = 8) was significantly higher than in Wistar (90 +/- 15%, n = 12, p = 0.0001) and Wistar-Kyoto rats (106 +/- 12%, n = 5, p = 0.005). The basal 2,3-DHBA level in SHR-SP rats was positively correlated (r = 0.831, n = 7, p < 0.05) with the degree of hypertrophy of the left ventricle expressed as the ratio of the left ventricle weight to the body weight. The data presented demonstrate that the hypertrophy of the left ventricle in SHR-SP rats is accompanied by the elevation of the level of free oxygen radicals.

The role of the central and peripheral I1-imidazoline and alpha 2-adrenergic receptors in the development of hypotension and bradycardia induced by the intravenous injections of moxonidine was studied, in stroke-prone spontaneously hypertensive (SHR-SP) rats. The intravenous and local injections of I1--alpha 2 antagonist efaroxan (Efa) into the rostral ventrolateral medula (RVLM) abolished the moxonidine-induced fall of blood pressure, but did not eliminate bradycardia. The alpha 2 antagonist yohimbine (Yoh) injected into RVLM did not influence the moxonidine effects, whereas the intravenous Yoh injections fully blocked these effects. Thus the hypotensive action of moxonidine is mediated predominantly by the I1-imidazoline RVMM receptors, while the heart rate decrease is partly realized via the alpha 2 adrenoreceptors of peripheral innervation.

Local injection of 4 nmol moxonidine (unilaterally) into the rostroventrolateral medulla of spontaneously hypertensive rats (SHR-SP) decreased mean blood pressure and heart rate by 24+/-3 and 3+/-4%, respectively. Pretreatment with the I1/alpha2-receptor antagonist efaroxan abolished the moxonidine-induced decrease in mean blood pressure, but had no effect on heart rate. Yohimbine blocked hypotension, delayed bradycardia (8 nmol), or completely inhibited the effects of moxonidine (16 nmol). Our results indicate that both I1-imidazoline receptors and alpha2-adrenoceptors of the rostroventrolateral medulla are involved in the realization of moxonidine-induced changes.

Study of the hemodynamic response (arterial pressure and heart rate) by radio- and telemetric techniques in stroke-prone hypertensive rats (SHR-SP) aged 6-7 months showed that a chronic oral administration of moxonidine at a daily dose of 2 and 10 mg/kg) leads to hypotension (7 +/- 3 and 21 +/- 5%, respectively) and bradycardia (5 +/- 1 and 14 +/- 5%, respectively). The moxonidine administration at a greater dose violated the circadian heart rate profile, reduced the motor activity of rats by 34 +/- 15%, and showed a drug dependence syndrome in the heart rate (but not in the arterial pressure). It is concluded that moxonidine administration at large doses may give rise to side effects.

Tetrindole (a tetracyclic antidepressant, reversible MAO inhibitor of the A type) and desipramine (a tricyclic antidepressant, nonselective inhibitor of the reverse catecholamine trapping) produce opposite hemodynamic effects in stroke-prone hypertensive rats (SHR-SP): tetrindole reduced, whereas desipramine increased, the heart rate and arterial pressure. Under the acute immobilization stress conditions in SHR-SP, tetrindole inhibited development of the post-stressor tachycardia, while desipramine did not change the heart rate and increased the arterial pressure.

The role of alpha 2-adrenergic and imidazoline receptors in the hemodynamic response to clonidine (manifested by reduced arterial pressure, heart rate, and renal blood flow rate) was studied by injecting their antagonists with different affinity (yohimbine and idazoxan) into narcotized Sprague--Dawley rats. The local introduction (microinjection into rostral ventrolateral medulla) and systemic administration (intraperitoneal injection) of the drugs showed that the hemodynamic effect of clonidine is mediated predominantly by the central alpha 2-adrenergic receptors, rather than by the imidazoline receptors.

A study on hybrids from reciprocal crossing of the SHR-SP and the WKY has shown that Y-chromosome and mitochondrial DNA the affect development of the spontaneous hypertension. The Y-chromosome takes part in disorders of baroreceptive sensitivity in phenylnephrine assay associated with hypertension. Although our findings suggest that structural remodelling of peripheral vascular resistance and an increase in noradrenaline-dependent vasocostriction is genetically determined in hypertensive rats, we could not corroborate the role of the Y-chromosome and mitochondrial DNA in the process. A difference was shown between male and female SHR-SP in the level of arterial pressure and in development of the vascular structure changes.

Anaphylactic response intensity was quantitatively estimated by means of measuring mean arterial pressure (MAP) and heart rate (HR). Damage to intestinal mucosa was studied by means of morphometry. These indices grew in a dose-dependent way along with the amount of administered egg ovalbumin (OVA). The MAP and HR measurements seem to be useful in a quantitative elucidation of allergic sensitivity in laboratory animals.

The nitrogen oxide NO-dependent regulation of the cerebral blood flow was studied before and after 24-hr head-down immobilization (HDI) of intact and pre-trained rats. Training consisted in 2-hr tail-suspension each day of the 2-wk period. Blood flow was determined with the laser Doppler flowmetry following local injection of a NO synthesis blocker (L-NAME), and NO (sodium nitroprusside). Neither HDI nor pre-training per se influenced NO tonic production in the cortex of large hemispheres and cerebellum. However, in pre-trained animals HDI resulted in a significant blood flow response to the local blockade of NO synthesis in the cerebellum. None of the animals changed the reaction of the blood flow to the local injection of sodium nitroprusside. The conclusion was drawn that alteration in the NO-dependent regulation of the brain blood flow in pre-trained animals could manifest of adaptation to HDI in the course of 24-hr suspension.

In the present study we investigated the chronopharmacological dependence of dose-dependent hypotensive and cardiochronotropic effects of the imidazoline-like drugs (clonidine, rilmenidine and moxonidine) in stroke-prone spontaneously hypertensive rats (SHR-SP), using radio-telemetric system (Data Sciences, USA). The 24-h blood pressure, heart rate and locomotor activity profiles showed peak values during the rats' active phase during the night period. The degree of hypotensive and bradycardic effects of all drugs were most evident at this time and occurred in the absence of a change in locomotor activity. These studies show that clonidine, rilmenidine and moxonidine decrease blood pressure and heart rate in a time-dependent manner in SHR-SP. It was demonstrated that the degree and duration of hypotensive action of imidazoline-like drugs vary with the time of drug administration.

Earlier findings have shown that hypotensive effects of centrally acting drugs, such as clonidine, are enhanced in animals after denervation of arterial baroreceptors. The purpose of this study was to investigate the dynamic of changes in arterial pressure, heart rate and hypotensive effects of clonidine, rilmenidine and moxonidine in Wistar rats after sino-aortic denervation (SAD) using radio-telemetry. SAD was followed by significant elevation of arterial pressure lability (the standard deviation of the mean arterial pressure), while the baseline mean arterial pressure (MAP) and heart rate in barodenervated rats (12 days after SAD) was similar to intact rats. The hypotension produced by clonidine, rilmenidine and moxonidine was much greater in SAD rats than in intact rats. The study suggests that baroreflex mechanisms are not only important for maintaining levels of blood pressure in the very short term, but also for buffering the effects of centrally acting antihypertensive drugs.

Dynamics of the transcapillary turnover of liquids in the brain and soft tissues of the head was studied in pre-trained small laboratory animals (rats) during antiorthostasis, and their controls. Training for antiorthostasis consisted of tail-suspension for 2 hours in the period of two weeks. The transcapillary turnover of liquids was determined based on the arteriovenous difference in blood density (AVBD). Blood density was measured with the equipment of Anton Paar K.G. (Austria). Rats in the horizontal position did not exhibit any apparent trend in the dynamics of blood transcapillary turnover. Blood drain from the interstitial space at the time of return of the antiorthostatic rats into the horizontal position was dependent on the length of antiorthostatis. Beginning from the fifth hour of tail suspension, changed AVBD sign was an indication of edema of the muzzle soft tissue. This phenomenon was not observed in the pre-trained rats. Similar results were obtained in the investigation of cerebral vessels AVBD. Hence, changes in the transcapillary turnover of liquids in cranium during antiorthostatic hypokinesia point to the dominance of liquid filtration into the extravascular space. Antiorthostatic pre-training precludes liquid deposition in the interstitial space of the brain and the cerebral soft tissue.

Changes in hemodynamic parameters in intravenous infusion of drugs of the clonidine group were studied in Wistar rats by means of the radio-telemetry and catheter systems of arterial pressure (AP) recording. Clonidine (5 micrograms/kg), rilmenidine (300 micrograms/kg), and moxonidine (100 micrograms/kg) were found to cause significant decrease in AD and bradycardia whatever the method of AD measurement used. However, the degree of the hypotensive and negative cardiochronotropic effects of the central action drugs was higher in rats with radio-telemetry transmitters. The results provide evidence that the radio-telemetry system of monitoring of the hemodynamic parameters is more sensitive and accurate for evaluating the effect of the drugs under study.

Radiotelemetric monitoring of hemodynamic parameters was conducted in Wistar rats to study the chronobiological dependence of the effect of clonidine on changes in arterial pressure (AP) and heart rate (HR) induced by immobilization stress. Clonidine injection (20 mg/kg intraperitoneally) caused significant decrease in AD at night both at rest and under stress, whereas at day time its hypotensive effect was manifested only in case of immobilization. The negative cardiochronotropic effect of clonidine was also time-dependent. Thus, chronobiological dependence of the clonidine effects at rest and under stress was disclosed.

A hypotensive effect of clonidine in non-narcotized intact and aorta baro-denervated rats is studied under conditions of minimization of stress actions (radiotelemetry) and under standard conditions of direct recording arterial pressure (AP). Direct AP recording is shown to determine an increase in background AP in baro-denervated rats, but not in control rats. An increase in background AP level under conditions of direct recording is not accompanied with decreasing hypotensive effect of clonidine in baro-denervated rats.

Changes in mean blood pressure (MBP), heart rate (HR), diuresis, natriuresis and kaliuresis, which had been evoked by intravenous bolus administration of the synthetic atrial natriuretic peptides (ANP) ANP (99-126), ANP (103-126), ANP (103-125), and ANP (103-123) in doses of 10 and 60 micrograms/kg each, were studied during 2% body weight volume expansion by intraarterial injections of 0.9% NaCl in awake rats. All the ANP analogues were indicated to decrease MBP and induce differential changes in HR. All the ANP analogues, except ANP (103-123), increased diuresis and natriuresis in the first 30 min of the experiment.

The effects of endothelin (0.1 nMol/kg and 1 nMol/kg into the left ventricle) on hemodynamics and cardiac contractility were investigated in conscious and unrestrained, WKY rats before and during continuous infusion of atriopeptides (1 microgram/kg/min i.v.). Bolus injection on endothelin into the left ventricle caused a transient hypotension and tachycardia followed by a long-lasting increase in mean blood pressure (MBP) and bradycardia in intact rats. In the rats receiving constant atriopeptide infusions, the hypotensive phase of endothelin effects was augmented whereas the hypertensive phase was reduced. Endothelin doses dependently increased cardiac contractility parameters during the first 3 minutes after injection. The stimulation of cardiac function at this time resulted from reflex responses due to the rapid decrease in the MBP. These effects were followed by decreases in cardiac contractility indices. Infusion of atriopeptide led to a tendency to the positive inotropic action of and augmented the negative inotropic action of endothelin.

The effects of endothelin (0.1 and 1 nmol/kg into the left ventricle) on mean blood pressure (MAP), heart rate (HR), central venous pressure (CVP), and mean circulatory filling pressure (MCFP) were investigated in conscious and unrestrained WKY rats before and during continuous infusion of atriopeptide (1 mu mk/kg/min i.v.). In intact rats, bolus injection of endothelin into the left ventricle caused a transient hypotension followed by a long-term increase in MAP. In the rats receiving atriopeptide infusion constantly, the hypotensive phase of endothelin effects was augmented whereas the hypertensive phase was reduced. Low doses of endothelin did not affect CVP and MCFP while the highest dose given to intact rats and atriopeptide-treated rats caused small, but significant decreases in CVP and MCFP. Our results suggest that endothelin has small effects on total body's venous tone in contrast to its effectiveness by increasing blood pressure.

Changes in parameters of systemic and regional hemodynamic, elicited by intraarterial administration of 250 or 500 mg/kg of 2-deoxy-D-glucose (2-DG) were studied in the awake Wistar rats with microsphere technique. Measurements were performed before, 15-and 40-min after 2-DG administration. Significant decrease in the heart rate as well as increase in stroke volume were observed 15 min after 2-DG. It was a tendency to increase in cardiac output. Blood flow in skin and skeletal muscles were decreased whereas in the brain, heart, adrenal glands and small intestine there were significant increases in the blood flow. We conclude that hemodynamic responses to 2-DG reflect the effects of humoral (adrenaline) and central sympathetic factors.

The systemic and regional hemodynamic effects of endothelin: a new vasoconstrictor peptide, were studied in alert WKY rats. The radioactive microsphere technique was used to measure cardiac output, total peripheral resistance and regional blood flow before and 10 min after bolus injection of endothelin into the left ventricle. Endothelin produced a transient hypotension followed by a long-lasting increase in blood pressure and in systemic resistance and a decrease in cardiac output. Endothelin induced a decrease in blood flow in all vascular beds to variable extent (the maximal changes were recorded in kidneys and adrenals), only the coronary blood flow being increased. In the rats receiving constant atriopeptine II infusion, the hypotensive phase of endothelin effects was augmented whereas the hypertensive phase was reduced. Atriopeptine II infusion also diminished the regional blood flow responses to endothelin in the kidneys, the adrenals and the heart.

Changes in the arterial pressure (AP), heart rate (HR) and sensitivity of chronotropic baroreceptor reflex (SBR) evoked by i. v. infusion of alpha-ANP, AP-III, AP-II, and AP-I (1 mg/kg/min) were studied in alert Wistar rats. The SBR was tested by infusion of phenylephrine or sodium nitroprusside. All the ANP analogues, except AP-1, were shown to decrease the AP and evoke differential changes in the SBR. The SBR evoked by phenylephrine was increased by 60-80%, whereas SBR evoked by sodium nitroprusside was decreased by 30-60%. The specific changes in tachycardic and bradycardic components of the baroreceptor reflex after ANP analogues infusions seem to reflect participation of the baroreceptor reflex in the mechanism of ANP-induced hypotension.

Changes of systemic and regional hemodynamic parameters of the rat during heating of the lower part of the body in 41 degrees C water and after removing of the testis from abdominal cavity, were measured with labeled microsphere technique. Experimental cryptorchism reduced the blood pressure due to a decrease in total peripheral resistance. Hyperthermia of the testis increased the heart rate. Heating of the scrotal region led to an increase in the blood flow that did not, however, reach the value of the blood flow in testis of the control unrestrained rats, thus suggesting an inadequate blood supply of the testis during heating. The inadequate blood supply of the testis under hyperthermia may be one of the factors leading to lesions of the testis.

Changes of the systemic and regional hemodynamics were studied in alert Wistar rats during their immobilization. Cardiac output and regional blood flows were measured with microsphere technique. The stress evoked 12% blood pressure increase, 30% cardiac output increase and 10% total peripheral vascular resistance decrease. Blood flow was increased in skeletal muscles, in the heart and adrenal glands, whereas in the kidney and small intestine blood flow decreased.

The radioactive microsphere technique was used to measure the cardiac output, regional blood flows and resistances in conscious rabbits and rats before and after 30-minute immobilization. Immobilization evoked blood pressure rise in both species. Cardiac output was reduced and total peripheral resistance increased in rabbits. Reverse changes of these parameters were observed in rats. Blood flow was reduced in the liver and the right ventricle in rabbits, and in the testes in rats. In immobilized rats, regional blood flow increased in skeletal muscles, the heart, the adrenals and the liver. These experiments demonstrate different hemodynamic mechanisms of immobilization-induced hypertension in rabbits and rats.

Administration of adrenaline for 5 days did not produce any effect on the mass and histostructure of rat testes. However, adrenaline overtly potentiated an adverse action of high temperature on spermatogenic function of the testicles (immersion of the scrotum into water heated to 41 degrees C for 30 min). That manifested in a further decrease in the testicular mass and an increase in the number of spermatic tubules which had lost two or more generations of germinal cells. It is assumed that the sensitivity of the testes to adrenaline rises under high temperature.

Systemic hemodynamic parameters in 5-month-old and 10-month-old normotensive Wistar-Kyoto and spontaneously hypertensive (SHR) conscious rats were studied with microsphere technique. Cardiac index was similar in both strains of rats and was not significantly different between 5 and 10 months. Left ventricle catheter implantation through the right common carotid artery evoked the development of heart failure in 10-month-old SHR (in the first day after operation). This model can be used for screening of new drugs for heart failure treatment.

Immersion of rat scrotum into water (41 degrees C) for 30 min leads to gross impairment of spermatogenesis. During incubation in Ringer-Krebs solution at 33 degrees C for 1h, fragments of the decapsulated testes taken from the heated rats secrete to the medium a high amount of substances that increase the optical density of the incubation liquid at 270 nm. This phenomenon can be recorded shortly after scrotum heating is completed. The optical density increases further 12 and 24 h after heating. During incubation, fragments of the testes heated in vivo also secrete a high amount of the lysosomal enzymes, acid phosphatase and cathepsin D. It is assumed that post-thermal degeneration of the spermatogenic epithelium may be determined by a change in the permeability of cellular and lysosomal membranes.