Principal vasoactive systems - renin-angiotensin system (RAS), sympathetic nervous system (SNS), nitric oxide (NO) and prostanoids - exert their vascular effects through the changes in calcium levels and/or calcium sensitization. To estimate a possible modulation of calcium sensitization by the above vasoactive systems, we studied the influence of acute and chronic blockade of particular vasoactive systems on blood pressure (BP) changes elicited in conscious normotensive rats by acute dose-dependent administration of Rho-kinase inhibitor fasudil. Adult male chronically cannulated Wistar rats were used throughout this study. The acute inhibition of NO synthase (NOS) by L-NAME enhanced BP response to fasudil, the effect being considerably augmented in rats deprived of endogenous SNS. The acute inhibition of prostanoid synthesis by indomethacin modified BP response to fasudil less than the acute NOS inhibition. The chronic NOS inhibition caused moderate BP elevation and a more pronounced augmentation of fasudilinduced BP changes compared to the effect of acute NOS inhibition. This indicates both short-term and long-term NOdependent attenuation of calcium sensitization. Long-term inhibition of RAS by captopril caused a significant attenuation of BP changes elicited by fasudil. In contrast, a long-term attenuation of SNS by chronic guanethidine treatment (in youth or adulthood) had no effect on BP response to fasudil, suggesting the absence of SNS does not affect calcium sensitization in vascular smooth muscle of normotensive rats. In conclusion, renin-angiotensin system contributes to the long-term increase of calcium sensitization and its effect is counterbalanced by nitric oxide which decreases calcium sensitization in Wistar rats., A. Brunová, M. Bencze, M. Behuliak, J. Zicha., and Obsahuje bibliografii
a1_Gastric lipase (GL) plays an important role in emulsification and digestion of food fat. Lipids are components of the hydrophobic mucus and mucosa barrier. Damage of the gastric mucosa may therefore be related to changes in the lipid content and GL activity. In the present paper, we studied the effect of administration of a single dose of 96 % ethanol (E) and indomethacin 20 mg.kg-1 (IND) on the activity of GL and on the concentrations of nonesterified fatty acids (NEFA) and triacylglycerols (TG) in the gastric mucosa of rats. Furthermore, we studied how these changes are affected by allopurinol (ALO), pentoxifylline (PX) and L-DOPA pretreatment 30 min before administration of E or IND. The effect of sialoadenectomy (SA) on these parameters was also evaluated. We found: 1) significant (p<0.01) inhibition of GL activity after administration of E and IND and also ALO, as well as after pretreatment with ALO before E and PX before IND. L-DOPA administered alone stimulated GL activity, but its administration before IND significantly (p<0.01) inhibited this enzymatic activity. GL activity was decreased to the threshold values in SA rats and after administration of E to SA animals. 2) NEFA concentrations were decreased after E and increased significantly (p<0.01) after IND administration. A marked significant (p<0.01) decrease in NEFA was found after PX and L-DOPA administration. The administration of ALO also lowered the concentration of NEFA. Pretreatment by drugs before E and IND resulted in a significant increase of NEFA in comparison with the drugs given alone (p<0.05 for ALO + E; p<0.01 for PX + IND). 3) TG were also decreased in all experimental groups in comparison with the control group, i.e. after E and IND, after ALO and SA and also after pretreatment by ALO before E. The concentration of TG decreased after PX, significantly (p<0.05) after L-DOPA and after pretreatment by PX before IND., a2_Pretreatment by ALO before E and L-DOPA before IND resulted in the increase of TG in comparison with drugs alone. Thus, these results suggest certain protective effect of pretreatment with ALO, PX and L-DOPA against the E- and IND-induced decrease in NEFA and TG during injury of the gastric mucosa. On the other hand, inhibition of GL activity was also apparent after administration of these drugs before E and IND, which suggest presence of a persisting impairment of lipid digestion in the stomach., A. Sedláková, A. Kohút, M. Šarišský., and Obsahuje bibliografii
Vasodilator prostaglandins (PGE2, PGI2) play an important role in the regulation of renal blood flow. Hence, inhibition of their production with nonsteroidal anti-inflammatory drugs increases renal vascular resistance and exerts adverse renal effects. It has been reported that besides endothelium-derived prostaglandin products, nitric oxide (NO) may be mainly involved in regulation of renal functions. The aim of our study was to evaluate the effect of cyclooxygenase inhibition with indomethacin and endothelium removal on vascular responses of the renal artery as a model vessel. Isolated segments of rabbit renal arteries were perfused at constant flow. Indomethacin administration (10-5mol.l-1) significantly increased the responses to single doses (0.1, 1, 10 m g) of noradrenaline (NA) as compared with the controls. In indomethacin-pretreated vessels, subsequent deendothelisation by air bubbles enhanced the constrictor responses to NA. In reversed order, when deendothelisation was followed by indomethacin administration, the responses to NA were similar in character. A comparison of renal artery responses to NA in both experimental situations did not reveal any significant differences. It can be supposed that endothelial and non-endothelial factors may be involved in local regulation of renal vascular tone., V. Kristová, M. Kriška, R. Vojtko, A. Kurtanský., and Obsahuje bibliografii
Stomach lesions induced by indomethacin (20 mg.kg'1 i.p.) and ethanol (1 ml 95 % intragastrically) were studied after a 24 hour fast in rats which had undergone sialoadenectomy. The size of the lesions was correlated with gastric HCI secretion, with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v, administration) and with the serum gastrin level. These parameters were also studied in sialoadenectomized rats and in animals given epidermal growth factor (EOF) (50 lg.kg'1). It was found that sialoadenectomy significantly (p<0.01) raised the incidence of stomach lesions after the administration of indomethacin and also after ethanol (p<0.05). A significant increase in both basal and stimulated HCI secretion was found after sialoadenectomy. Both indomethacin and ethanol also increased gastric vascular permeability in rats not subjected to sialoadenectomy, but sialoadenectomy raised it significantly compared with the non-sialoadenectomized group. The serum gastrin levels fell after sialoadenectomy and the decrease was significant after the subsequent administration of indomethacin or ethanol.The administration of EGF to sialoadenectomized rats lowered the incidence of stomach lesions, inhibited HCI secretion and reduced vascular permeability. The lowered susceptibility of the gastric mucosa to the formation of lesions in sialoadenectomized rats given indomethacin or ethanol can be regarded as the outcome of the uptake of EGF.
Malotilate as a synthetic substance shares comparable hepatoprotective properties with various flavonoids. The gastroprotective effect of some flavonoids prompted us to ascertain the similar effectiveness of malotilate. The possible gastroprotectivity was examined in gastric mucosal damage in rats induced by indomethacin (20 mg.kg-1) or ethanol (96 %). Oral pretreatment with malotilate (25, 50, 100, 200 and 400 mg.kg-1) reduced the extent of lesions induced by both indomethacin and ethanol. Histological analyses also revealed a mitigating effect on the severity of gastric mucosal lesions. Similar results were obtained in the group of rats pretreated with 5 mg.kg-1 indomethacin followed by oral administration of 96 % ethanol. This finding suggests that the effect of malotilate on rat gastric mucosa is independent of endogenous prostaglandin production.
Pentoxifylline pretreatment protects rat gastric mucosa against indomethacin-induced damage. Lipid peroxidation after indomethacin treatment (determined as thiobarbituric acid reactants) was significantly reduced by a single dose of pentoxifylline. The same was true for pentoxifylline administration for 6 days. There is a relationship between reduced lipid peroxidation, decreased number of circulating activated neutrophils and diminished disposition for acute gastric mucosal lesions induced by indomethacin in pentoxifylline-pretreated rats.
This study was designed to determine the gastroprotective properties of quercetin in ischemia/reperfusion-induced gastric mucosal injury and the involvement of endogenous prostaglandins in this process. Oral pretreatment of rats with quercetin (100 mg.kg-1) 30 min before surgery significantly decreased the length of gastric mucosal lesions. However, lower doses of quercetin (25 and 50 mg.kg-1) only slightly decreased the gastric mucosal injury. Intraperitoneal application of indomethacin (5 mg.kg-1) had no effect in control (sham-operated) animals, but significantly worsened gastric injury in non-treated animals after ischemia/reperfusion. Furthermore, indomethacin only slightly reversed protective effect of quercetin. Non-treated animals showed a marked decrease in adherent mucus after ischemia/reperfusion. On the other hand, application of quercetin prevented this significant decrease even in animals pretreated with indomethacin. It can be concluded that antioxidant properties of quercetin and its mucus protective effect might be the main factors responsible for its protective effect against ischemia/reperfusion-induced gastric mucosal injury., J. Mojžiš, K. Hviščová, D. Germanová, D. Bukovičová, L. Mirossay., and Obsahuje bibliografii
Fever developing after intracerebral injections of lipopolysaccharide (LPS) to guinea-pigs were monophasic, with only one peak of inner body temperature,slowly developing and longlasting in a dose range 20 to 200 ng of LPS. Latency time was inversely related to the dose of LPS. Indomethacin injected to the third brain ventricle did not abolish fever response.