Acta physiologica et pharmacologica Bulgarica最新文献

The anterior hypothalamus (AH) participates in the regulation of arterial pressure. The suprachiasmatic nuclei (SCN) of the AH are a major circadian oscillator necessary for the generation and/or the entrainment of circadian rhythms. Circadian rhythms of systolic arterial pressure (SAP) and heart rate (HR) were investigated in spontaneously hypertensive rats (SHR) and in normotensive Wistar rats (NWI) with intact SCN, grafted with SHR embryonic AH tissue containing the SCN. Prominent circadian rhythms for SAP and HR in both NWI and SHR with acrophases during dark were found. The elevation of the MESOR (midline-estimated statistic of rhythm) of the SAP in normotensive rats grafted with AH embryonic tissue obtained from SHR was accompanied by disappearance of the circadian rhythm of SAP. This result suggests an interaction between the grafted tissue containing the SCN on the one hand, and the host SCN on the other hand. Our data ascribe a role for the SCN in the entrainment of the circadian rhythm of arterial pressure. The circadian rhythm of HR was not eliminated by the SCN graft in spite of the amplitude decrease and the phase delay observed. It seems that the entrainment of the circadian rhythm of HR is probably not crucially dependent on the SCN in rats. The circadian rhythms of SAP and HR in rats were differently affected by the grafts, thus suggesting a multioscillatory system for circadian regulation in rats.

The effects of age on the 5-hydroxytryptamine-immunoreactive (5-HT-IR) neurons in raphe and extrarapheal nuclei of rats were examined using morphometry. Quantitative parameters of the neuronal density and cross-sectional areas of the cell bodies as well as of the length and numbers of the processes of the 5-HT-IR neurons were analyzed in 3-, 12- and 26-month-old-rats. The results showed that aging affected the 5-HT-IR neurons in the rat brainstem nuclei. The age-related changes in the immunostaining pattern and quantitative parameters were more or less pronounced and earlier or later developed depending on the nucleus studied. It is most probably connected with specific functions and projections of each raphe nucleus.

The electrical activity of the descending colon of fifteen healthy volunteers was recorded non-invasively by cutaneous electrodes sticked on the abdominal wall along the descending colon projection--electrocologram (EColG). The electrical activity of the colon and stomach was recorded by an original electrogastrograph. The means, S.E.M. of the frequency of the colonic and gastric waves were calculated. Parallel studies of the EColG and the changes in the intracolonic pressure were performed on 10 patients with balloon inflated in the colon. Two kinds of EColG waves according to their frequency were identified: i) Type A waves with a frequency of 5.86 +/- 0.59 cpm and ii) Type B waves with a frequency of 2.35 +/- 0.25 cpm. There was a significant difference between the frequencies of the EColG waves and the frequency of the EGG waves -3.35 +/- 0.31 cpm. The type A waves were of low amplitude and corresponded to type A dog colonic waves i.e. they characterized the quiescent period of colonic motility. Type B waves were with a high amplitude, corresponded to type B dog colonic waves and characterised the activity periods of colonic motility. This was confirmed by the correspondence between type B waves and the changes in the intracolonic pressure. Thus the proposed non-invasive electrogastrographic method proved to be suitable for non-invasive registration of the electrical activity of the human colon.

Immunohistochemistry and morphometry were used to study the age-related changes in the vasopressin (AVP) and oxytocin (OXT) nerve cells in the paraventricular (PVN), supraoptic (SON) and suprachiasmatic (SCN) nuclei of 3-, 11- and 28-month-old rats. The results showed a statistically significant reduction in the mean number of AVP cells in the PVN, SON and SCN, and of OXT cells in the PVN with advancing age. Different age-related changes in the mean size of the immunoreactive cells were found in the three nuclei: a significant and transitory increase in the AVP and OXT cell sizes in the PVN, a tendency towards increasing the AVP and OXT cell sizes in the SON, and a significant and gradual decrease in the AVP cell size in the SCN. The combination of the morphometric data and staining patterns of the AVP and OXT perikarya and fibers in the PVN and SON pointed to an increased transport of AVP and OXT in 11-month-old rats as well as to a decreased production of these peptides in the PVN of 28-month-old rats. Taken together the staining pattern and the morphometric results showed a progressive loss of AVP cells in the SCN in aging.

Chronic experiments were performed on dogs with silver, bipolar, ball-shaped electrodes implanted on the colonic and of the gastric muscle wall. Cutaneous electrodes were placed on the abdominal wall, along the projection of descending colon and also of the stomach, at the beginning of each experiment. Slow waves were led off in the electrocolomyogram (EColMG), corresponding to low-amplitude waves in the non-invasive electrocologram (EColG) with a frequency of 6.39 +/- 0.58 cpm (type A). When bursts of spike potentials appeared with the slow waves in the EColMG, increase of the amplitude of the EColG waves and decrease of the frequency (1.90 +/- 0.20 cpm) was observed. There was a significant difference between the colonic wave frequency and the frequency of the gastric waves (3.96 +/- 0.28 cpm). A good correlation was found between the number and frequency of the spike potentials in a group in the EColMG and the wave amplitude in the EColG. A sequence of low-frequency, high-amplitude waves (type B) characterized an activity period, while a sequence of low-amplitude, high-frequency waves (type A) corresponded to a quiescent period of the colonic motility. Thus the functional state of the colonic muscle wall could be judged by the differences in the frequency and amplitude of the EColG waves.

The possible relationship between coffee exposure during pregnancy and the teratopharmacological effects on the developing neonates was evaluated in albino mice. The body weight of pups of treated dams was significantly affected after birth and as the pups grew, their weight gains were lower compared to controls. This effect was time- and dose-dependent and the perinatal treatment was more effective (F(6) = 5.06, p < 0.02) than the prepartum treatment (F(6) = 3.12, p < 0.05). Body hair appearance and eye opening were delayed in all treated groups and again, the perinatal treatment was more effective and dose-dependent. Almost all indices for "locomotor behavior" were affected by all doses of coffee but only in the perinatally treated groups and the effects were neither time- nor dose-dependent. In the "tube restraint test", the latency to the first bite was decreased and the number of bites was increased in the offspring, while in female offspring the effect was opposite. The body weight of female offspring remained low even in young adult animals (F(6) = 9.89, p < 0.005). The brain weight in males was unaffected but in females it was decreased but only at the dose of 2 mg/kg. The liver and kidney weights of both sexes decreased at the lower doses. The protein content of these organs was also significantly affected by coffee treatment. These results suggest that coffee intake during pregnancy should be limited since it produces significant and long-lasting teratopharmacological and behavioral alterations in the offspring.

The routine procedure for analysing the drug action on isolated organs is the establishment of the dose-response relationship and its quantification. In the first part of the experiment, we established the dose-response relationship for acetylcholine, carbachol, betanechol and 5-hydroxytriptamine on isolated preparations of rat fundus. In the second part, we analyzed the development in time of the rat fundus response to a single concentration of each of the four agonists. The single concentrations used were slightly higher than the EC50 of the agonists eliciting an optimal response. Responses to betanechol and carbachol developed with essentially the same rate, while responses to acetylcholine and 5-hydroxytriptamine developed more rapidly and more slowly, respectively. Since the rate of response development is highly dependent on the type of the receptor the agonist activated, analysis of response development in time could be an useful adjunctive tool in the pharmacodynamic studies.

Circadian patterns of wheel-running activity were studied in male Wistar rats before, during, and after continuous infusion of (Pmp1, Tyr(Me)2)-Arg8-vasopressin, a V1 receptor antagonist, in the suprachiasmatic region by means of Alzet mini-osmotic pumps. The lack of any significant effect on the pattern of wheel-running activity argues against a role for vasopressin in the generation of circadian rhythms by the suprachiasmatic nuclei.

The effect of chenodeoxycholic acid on liver monooxygenase system, lipid peroxidation, lymphocyte proliferation, and immune complexes formation was studied in carbontetrachloride-treated rats. Chenodeoxycholic acid increased the content of both cytochrome P-450 and cytochrome b5 and the rate of aminopyrine N-demethylation in liver microsomal fractions. It also normalized lipid peroxidation in the liver and the proliferative activity of blood lymphocytes activated by phytohemagglutinin. Soon after injection chenodeoxycholic acid caused disturbances of the liver histostructure and of the microcirculation followed by regenerative processes. Liver histostructure tended to return to normal. The level of serum immune complexes was increased. The relationship between the changes in monooxygenase system, lipid peroxidation and immunologic parameters is discussed.

The effects of Verapamil and Diltiazem, administered at a dose of 0.3 mg/kg i.v., on the autoregulation of the regional cerebral blood flow (rCBF) in the cortex and the thalamus were studied on 28 cats. The animals were anesthetized with ether and alfa-chloralose. The rCBF was registered by the hydrogen clearance method with locally generated hydrogen. The mean arterial blood pressure (MABP) elevation was performed by an i.v. infusion of angiotensin (0.2 microgram/min). The mean initial values of the cortical rCBF were 71.15 ml/100g/min and of the thalamic rCBF -46.85 ml/100 g/min. The mean limits of the cortical rCBF autoregulation were: 137.5 mm Hg for the absolute limit (La) and 31.25 mm Hg for the relative limit (Lr). The mean limits of the thalamic rCBF autoregulation were: 157.75 mm Hg for the (La) and 46.5 mm Hg for the (Lr). Verapamil increased the cortical rCBF by 40% and the thalamic rCBF by 24%. The absolute limits of rCBF autoregulation were decreased by 22% in the cortex, and by 15% in the thalamus. The relative limits were decreased by 31% in the cortex and by 35% in the thalamus. Diltiazem increased the cortical rCBF by 42% and the thalamic rCBF by 6%. The absolute limits of rCBF autoregulation were decreased by 21% in the cortex and the thalamus. The relative limits were decreased by 52% in the cortex, and by 38% in the thalamus.