Experiments were performed in C57BL/6J male mice to determine the effects of acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB) and stress on cardiovascular function, structure, and apoptosis. Mice were studied for seven days under the following conditions: Controls (osmotic minipump with saline), PB (10 mg/kg/day, minipumps), shaker stress (45 stressors/day, minipump with saline) and PB+Stress combination. AChE activity was significantly reduced in all PB-treated mice. PB caused no changes in 24-h mean arterial pressure (MAP) or heart rate (HR). Stress
increased 24-h MAP on day 1 and 24-h HR on day 7 in both Stress and PB+Stress groups. A significant reduction in the aortic wall thickness/diameter ratio (P <0.05 vs. control) and slightly reduced relative heart weight were observed in the PB group. These effects were blunted by simultaneous stress exposure. Immunochemistry was used to stain for Bax and Bcl-2 (apoptosis markers). There was a four-fold increase in Bax/Bcl-2 ratio in the heart of PB and PB+Stress treated mice while an attenuation was observed in aortic endothelium. Results suggest that a relatively short-term continuous PB exposure may have adverse effects on the heart and blood vessels, independently of changes in MAP and HR.
The interrelationship between baroreflex sensitivity expressed in ms/mm Hg (BRS) or in Hz/mm Hg (BRSf), carotid wall thickness (IMT), and age was investigated in hypertensive and normotensive subjects with respect to the mean inter-beat interval (IBI) and blood pressure (BP). BP monitoring was performed in 25 treated hypertensives (Hy; 47.4±9.2 years of age) and 23 normotensives (Norm; 44.5±8.1 years). IMT was measured by ultrasonography. BRS and BRSf were determined by the spectral method (five-minute non-invasive beat-to-beat recording of BP and IBI, Finapres, controlled breathing at a frequency of 0.33 Hz). Significant differences between Hy and Norm were detected in IMT (Hy: 0.624±0.183, Norm: 0.522±0.070 mm; p<0.01), BRS (Hy: 3.5±1.6, Norm: 5.7±2.3 ms/mm Hg; p<0.01), BRSf (Hy: 0.005±0.002, Norm: 0.009±0.004 Hz/mm Hg; p<0.01), systolic BP (Hy: 131±21, Norm: 116±17 mm Hg; p<0.01) and diastolic BP (Hy: 77±16, Norm: 64±12 mm Hg; p<0.01). A significant correlation was found between age and IMT (Norm: 0.523, p<0.05; Hy+Norm: 0.419, p<0.01), age and BRS (Norm: -0.596, p<0.01; Hy+Norm: -0.496, p<0.01), age and BRSf (Norm: -0.555, p<0.01; Hy: -0.540, p<0.01; Hy+Norm: -0.627, p<0.01), age and IBI (Hy: 0.478, p<0.05), age and diastolic BP (Hy: -0.454, p<0.05), BRS and IMT (Hy+Norm: -0.327, p<0.05) and BRSf and IMT (Hy+Norm: -0.358, p<0.05). Hypertensive patients have increased IMT and decreased BRS and BRSf. The positive correlation between age and IMT and the negative correlation between age and BRS and BRSf are in agreement with the hypothesis that the age-dependent decrease of baroreflex sensitivity corresponds to the age-related structural changes of the carotid wall. Using two indices of baroreflex sensitivity, BRS and BRSf, we could show that baroreflex sensitivity in hypertensives is lower not only due to thickening of the carotid wall, but also due to aging.
The aim of this study was to ascertain the persistence of heart rate and blood pressure oscillations at the onset of voluntary apnea in humans and to assess the dependence of the fluctuations` parameters on the chemoreceptor activity. In 24 young subjects (10 males, 14 females, mean age 20.4 years) heart rate (represented by its reciprocal value - RR-intervals), systolic blood pressure (SBP) and diastolic blood pressure (DBP) during controlled breathing (CB) of atmospheric air and oxygen followed by apnea were recorded continuously. The cosine functions were then fitted by nonlinear regression analysis to the heart rate, SBP and DBP oscillations during CB and at the onset of apnea. The parameters of oscillations were different during atmospheric air breathing compared to oxygen breathing. During oxygen breathing there was an increase of the RR-interval oscillations - relative bradycardia and enhanced magnitude of respiratory sinus arythmia. During apnea, the base level of the blood pressure oscillations was higher after breathing of atmospheric air compared o oxygen breathing. At least one cosine-like wave oscillation was present at the onset of apnea in the heart rate, SBP and DBP and the second wave was present in all assessed parameters in at least 70 % of recordings. The oscillations in RR-intervals are, to some extent, independent of blood pressure oscillations. No significant gender differences were found either in the duration of breath holding or in the RR and SBP oscillations parameters., M. Javorka, I. Žila, K. Javorka, A. Čalkovská., and Obsahuje bibliografii
We reported previously that the nitric oxide synthesis inhibitor Nv-nitro-L-arginine methyl ester (L-NAME) decreases cardiac output. Several studies have shown that inhibition of nitric oxide synthesis decreases the heart rate. In the present study, we investigated the effect of a single bolus administration of L-NAME on blood pressure and heart rate monitored for one hour in anesthetized rats and the influence of vagotomy and b1-receptor blocker metoprolol on the L-NAME induced bradycardia. After L-NAME treatment, the blood pressure rose immediately after the injection of the drug (peak response in the third minute: +24 %, p<0.001) and fell to the control level in the 20th minute. The heart rate decreased immediately after L-NAME administration, the lowest value being reached in the 10th minute (-14 %, p<0.001). However, bradycardia was sustained even after the blood pressure had returned to the control level. Bilateral vagotomy failed to influence the negative chronotropic effect of L-NAME, but bradycardia was completely abolished by metoprolol pretreatment. We concluded that the bradycardia evoked by L-NAME is mainly due to the withdrawal of sympathetic tone upon the heart rate. However, the cause of sustained bradycardia after normalization of blood pressure cannot be elucidated., J. Vág, C. Hably, J. Bartha., and Obsahuje bibliografii
Cardiovascular effects of LVV-hemorphin-7, a member of the family of fragments from β-chain of human or bovine hemoglobin, were studied in conscious spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats by radiotelemetry. Intraperitoneal injection of hemorphin in a dose of 100 g/kg significantly decreased blood pressure in SHR, whereas negligible effect was seen in normotensive WKY rats. Blood pressure changes were accompanied by reduction of heart rate. In conclusion, a direct effect of LVV-hemorphin-7 on blood pressure was demonstrated in SHR. These biologically active peptides could be involved in blood pressure regulation especially in hypertensive rats, but the precise mechanism should be elucidated.