In this study, we investigated the effects of Nw -nitro-L-arginine (L-NNA) on arterial blood pressure (BP), plasma noradrenaline (NA) and adrenaline (A) levels and angiotensin-converting enzyme (ACE) activity. L-NNA was applied with tap water (1 mg/ml) from the 3rd to the 8th week of age (group L-NNA1). In Experiment 1, long-term L-NNA application increased BP compared to the control group (group C1) (L-NNA1 = 131.4 ± 6.3, n=6; C1= 82.7 ± 4.7 mm Hg, n=7) but decreased plasma noradrenaline and adrenaline levels and ACE activity (NA levels: C1 = 15.5 ± 0.8, n=7; L-NNA1= 8,6 ± 0.5 ng/ml, n=7; A levels: C1 = 15.5 ± 0.8, n=7; L-NNA1 = 6.0 ± 0.5 ng/ml, n=7; ACE activities: C1= 87.3 ± 3.1, n=6; L-NNA1 = 46.2 ± 1.9 U/l, n=5). On the other hand, in Experiment 2 (carried out under the same conditions and in age-matched chickens), blood pressure, plasma noradrenaline levels and ACE activity were found to differ in the control group (C2) (BP=141.4 ± 15.5 mm Hg, n=7; NA =1.1 ± 0.4 ng/ml, n=7; ACE = 57.2 ± 5.3 U/l, n=7) as compared to C1, while plasma adrenaline levels were similar. In this series, long-term L-NNA application (group L-NNA2) did not change the BP, but surprisingly increased noradrenaline and ACE values (values of L-NNA2: BP = 165.7 ± 15.6 mm Hg, n=7; NA = 9.3 ± 1.3 ng/ml, n=8; ACE = 149.4 ± 16 U/l, n=8) while decreasing plasma adrenaline levels. L-arginine addition to L-NNA treatment completely reversed plasma noradrenaline and ACE activity values. These results indicate the modulatory activity of an L-arginine-NO pathway on adrenaline release as well as on the renin-angiotensin system in chickens., H. E. Aksulu, I. Bingöl, F. Karatas, H. Sagmanligil, B. Üstündag., and Obsahuje bibliografii
This study aimed to investigate the effects of chronic restraint stress (CRS) on the protein levels of dopamine-β-hydroxylase (DBH), noradrenaline transporter (NET), vesicular monoamine transporter 2 (VMAT2) and brain-derived neurotrophic factor (BDNF), as well as the concentration of noradrenaline (NA) in the rat hippocampus. The investigated parameters were quantified by Western blot analyses and ELISA kits. We found that CRS increased the protein levels of DBH by 30 %, VMAT2 by 11 %, BDNF by 11 % and the concentration of NA by 104 %, but decreased the protein levels of NET by 16 % in the hippocampus of chronically stressed rats. The molecular mechanisms by which CRS increased the hippocampal NA level are an important adaptive phenomenon of the noradrenergic system in the stress condition.
The role of neuroendocrine responsiveness in the development of orthostatic intolerance after bed rest was studied in physically fit subjects. Head-down bed-rest (HDBR, -6 degrees, 4 days) was performed in 15 men after 6 weeks of aerobic training. The standing test was performed before, after training and on day 4 of the HDBR. Orthostatic intolerance was observed in one subject before and after training. The blood pressure response after training was enhanced (mean BP increments 18±2 vs. 13±2 mm Hg, p<0.05, means ± S.E.M.), although noradrenaline response was diminished (1.38±0.18 vs. 2.76±0.25 mol.l-1, p<0.01). Orthostatic intolerance after HDBR was observed in 10 subjects, the BP response was blunted, and noradrenaline as well as plasma renin activity (PRA) responses were augmented (NA 3.10±0.33 mol.l-1, p<0.001; PRA 2.98±1.12 vs. 0.85±0.15 ng.ml-1, p<0.05). Plasma noradrenaline, adrenaline and aldosterone responses in orthostatic intolerant subjects were similar to the tolerant group. We conclude that six weeks of training attenuated the sympathetic response to standing and had no effect on the orthostatic tolerance. In orthostatic intolerance the BP response induced by subsequent HDBR was absent despite an enhanced sympathetic response., J. Koška, L. Kšinantová, R. Kvetňanský, M. Marko, D. Hamar, M. Vigaš, R. Hatala., and Obsahuje bibliografii
Numerous studies concerning the cardiovascular system in SHR often yield controversial data. The background of this diversity has various roots, ranging from different vascular segments or areas studied up to the different age of experimental animals. Our study aimed to follow the BP as an integrated response of vascular system. This approach was justified since stabilized cardiac output in SHR was proved till 1 year of age. The groups of male SHR (aged 3, 5, 9, 17 and 52 weeks) and age-matched Wistar rats were used. Significant basal BP difference between SHR and Wistar rats was found at 9 weeks of age and continued till the age of 52 weeks, reaching 189.6±11.9 mm Hg in SHR and 117.3±6.9 mm Hg in Wistar rats (P<0.01). The significant difference in BP increase to two doses of noradrenaline (0.1μg and 1 μg) between SHR and control rats was also found at the age of 9 weeks. At 52 weeks the BP increment to two doses of noradrenaline was in SHR 19.7±2.0 mm Hg and 60.5±3.9 mm Hg and in Wistar rats 7.4±1.9 mm Hg and 40.5±3.2 mm Hg (P<0.01). The hypotensive response to acetylcholine (0.1 μg, 1 μg and 10 μ) in SHR was enhanced at 17 weeks of age only and this amplification persisted till the age of 52 weeks. In 52-week-old SHR the hypotensive response to three doses was 69.9±10.2 mm Hg, 87.5±11.8 mm Hg and 103.4±10.6 mm Hg, while in Wistar rats it was 37.4 4.2 mm Hg P<0.0), 62.3±3.5 mm Hg (P<0.01) and 73.5±2.8 mm Hg (P<0.05). In conclusion, the efficiency of cardiovascular system of SHR to respond to noradrenaline was already enhanced from 9 weeks of age, whereas the response to acetylcholine was not augmented before the age of 17 weeks., M. Gerová, F. Kristek., and Obsahuje bibliografii a bibliografické údaje
Little is known about the effect of chronic angiotensin-converting enzyme inhibition on the catecholamine levels in fowls. In this study, we investigated the effects of chronic lisinopri1 dihydrate (Ld) application on the plasma levels of adrenaline and noradrenaline and on the blood pressure. Lisinopril was given in different concentrations (25, 75 and 250 mg/l drinking water) to the white Leghorn chickens for 9 weeks, while the control group drank tap water only. Twenty-eight hours after the last lisinopril application, arterial blood pressure (BP), plasma adrenaline and noradrenaline levels, plasma renin (PRA) and plasma angiotensin-converting enzyme (ACE) activities were determined. In all concentrations, lisinopril significantly increased PRA and decreased ACE activities. Arterial BP was decreased only in the group receiving high lisinopril concentration (Controls 119±10.27, Ld3 98±5.4 mm Hg). However, the lower lisinopril concentrations did not alter arterial BP compared to the control group. Plasma noradrenaline levels were decreased in a concentration-dependent manner (47-58 %), but plasma adrenaline levels remained unchanged. The heart weight/body weight ratio was not changed in any of the lisinopril-treated groups. The persistent decrease in the blood pressure after lisinopril treatment was not directly related to a decrease of plasma ACE activity or plasma noradrenaline levels. Its mechanism still remains to be elucidated., H. S. Ozdemir, H. E. Aksulu, F. Karataş, B. Ustündag, I. Bingöl., and Obsahuje bibliografii
Recent results of the authors have demonstrated that the elevation of extracellular adenosine induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), a soluble adenosine prodrug, mediates radioprotective effects in mice. Furthermore, it has been shown that this action is induced by at least two mechanisms: (1) protection by hypoxia as a result of the effects of treatment on the cardiovascular system (bradycardia, vasodilation), and (2) an enhanced regeneration of the radiation-perturbed hematopoiesis. Here, it was ascertained that the joint use of an optimal dose of noradrenaline given with dipyridamole and AMP combination eliminates the hypothermic and hypoxic effects of the treatment, but preserves the radioprotective action of dipyridamole and AMP combination in terms of hematopoietic recovery and partially also survival enhancing effects of the drugs in gamma-irradiated mice. These findings might be of importance for attempts to obtain available and tolerable radioprotective pharmacological prescriptions for clinical use.
Cardiovascular and neuroendocrine responses to exercise in a physically fit and an untrained group of young healthy subjects were compared to study the significance of physical fitness for performance in a discipline for which the athletes were not trained. Ten wrestlers of national rank prepared for an international competition (age 18 years) and 9 untrained healthy males (age 21 years). Exercise consisted of 27-min swimming, freestyle, in water of 29 °C, with last 3 min increased to maximal effort. The blood pressure, heart rate and sublingual temperature were measured and blood samples were withdrawn before exercise, immediately after and after a 30 min period of rest. Catecholamines were analyzed by radioenzymatic method and plasma renin activity (PRA) using commercial kits. Systolic blood pressure and heart rate after swimming were increased comparably in the two groups, diastolic pressure was unchanged in the controls and decreased in the wrestlers. Plasma cortisol remained unchanged. Plasma glucose tended to increase in the controls and so decrease in wrestlers, with a significant difference between them after swimming (p<0.05). However, plasma adrenaline was concomitantly increased in both groups (p<0.01). Noradrenaline and PRA were increased after swimming in both the control and trained group. The increments of noradrenaline and PRA in wrestlers were significantly reduced compared to the control group (p<0.01, p<0.05, respectively). Higher physical fitness in athletes significantly reduced plasma noradrenaline and angiotensin responses to maximal exercise demanding special skill in work performance which had not been included in their training program. Training of wrestlers did not cause an exaggerated plasma adrenaline response to exercise.
We investigated the effect of pertussis toxin (PTX) on hypotensive response induced by acetylcholine (ACh) and bradykinin (BK) and on noradrenaline (NA)-induced pressor response in spontaneously hypertensive rats (SHR). Fifteen-week-old Wistar rats and age-matched SHR were used. Half of SHR received PTX (10 μg/kg/i.v.) and the experiments were performed 48 h later. After the anesthesia the right carotid artery was cannulated in order to record blood pressure (BP). The hypotensive response to ACh was enhanced in SHR compared to Wistar rats. After pretreatment of SHR with PTX the hypotensive response to ACh was reduced compared to untreated SHR and it was also diminished in comparison to Wistar rats. Similarly, the hypotensive response to BK was also decreased after PTX pretreatment. The pressor response to NA was increased in SHR compared to Wistar rats. NA-induced pressor response was considerably decreased after PTX pretreatment compared to untreated SHR. In conclusion, the enhancement of hypotensive and pressor responses in SHR was abolished after PTX pretreatment. Our results suggested that the activation of PTX-sensitive inhibitory Gi proteins is involved in the regulation of integrated vasoactive responses in SHR and PTX pretreatment could be effectively used for modification of BP regulation in this type of experimental hypertension., S. Čačányiová, F. Kristek, J. Kuneš, J. Zicha., and Obsahuje bibliografii a bibliografické odkazy
The potassium channel opening drug, pinacidil, has been examined in isolated perfused lungs taken from rats with hypoxic pulmonary hypertension (housed in 10 % oxygen for 7 days) and control rats. Inhibition by pinacidil (1 to 30 //M) of noradrenaline (NA)-induced vasoconstriction (NA infusions; /^-adrenoceptors blocked) and of hypoxic pulmonary vasoconstriction (HPV; ventilation for 3.5 -4.5 min with 0-1 % oxygen) were compared. The vasoconstrictor responses in preparations from control and hypoxic rats, respectively, were (mm Hg) NA 6.6±0.68 (6); 8.2±1.45 (9); HPV 7.8±1.03 (12); 8.8±0.93 (13). These responses were reversibly inhibited by pinacidil. In lungs from control rats pinacidil was 10-fold less potent against NA than against HPV, but in lungs from hypoxic rats it was equipotent against NA and HPV. When tested against NA, but not HPV, pinacidil was significantly more potent in lungs from hypoxic rats than control rats. It is postulated that NA-induced vasoconstriction in lungs from hypoxic rats, and HPV in both groups of rats, involve calcium influx through voltage-operated calcium channels. Consequently, these responses are readily inhibited by drugs such as pinacidil which open potassium channels and hyperpolarise the cell membrane. In contrast in lungs from control rats, NA-induced constriction may involve mainly intracellular calcium release and thus be less readily inhibited by the hyperpolarising effect of pinacidil.