Variations in Chemical Composition, Vasorelaxant and Angiotensin I-Converting Enzyme Inhibitory Activities of Essential Oil from Aerial Parts of Seseli pallasii Besser (Apiaceae).

The present paper describes environmental and seasonal-related chemical composition variations, vasorelaxant and angiotensin I-converting enzyme (ACE) activities of essential oil from aerial parts of Seseli pallasii Besser. The composition was analyzed by GC and GC/MS. Monoterpenes were found to be the most abundant chemical class with α-pinene (42.7 - 48.2%) as the most prevalent component. Seseli pallasi essential oil relaxed isolated endothelium-intact mesenteric arteries rings precontracted with phenylephrine with IC50  = 3.10 nl/ml (IC50  = 2.70 µg/ml). Also, S. pallasii essential oil was found to exhibit a dose-dependent ACE inhibitory activity with an IC50 value of 0.33 mg/ml. In silico evaluation of ACE inhibitory activity of the individual components showed that spathulenol exhibited the best binding affinity with ACE, and the lowest binding energy of -7.5 kcal/mol. The results suggested that combination of vasorelaxing and ACE inhibitory effects of the analyzed S. pallasii essential oil might have the potential therapeutic significance in hypertension.

Effect of indometacin pretreatment on protamine sulfate-mediated relaxation of the isolated rat uterus: the role of the antioxidative defense system.

Previous results in this laboratory indicate that protamine sulfate (PS) evokes dose-dependent relaxation of both spontaneous and calcium ion-induced uterus activity mediated predominantly by potassium channels and, to a small extent, via ß-adrenergic receptors or nitric oxide (NO)-dependent pathways. Indometacin is a nonselective inhibitor of cyclooxygenase (COX 1 and COX 2) that has the ability to delay premature labor by reducing uterine contractions through the inhibition of prostanglandin synthesis in the uterus. This study investigates the effects of indometacin (0.1 and 1 µg/ml) pretreatment on the PS-induced relaxation of isolated uterine smooth muscle. Indometacin pretreatment per se did not change the activity of the uteri. However, indometacin significantly increased PS-induced relaxation of spontaneous uterine contractions. Indometacin pretreatment significantly decreased the magnitude and slope of PS-induced relaxation of calcium ion-induced uterine contractions. Indometacin pretreatment increased CuZnSOD activity and slightly increased GR activity during spontaneous uterine contractions when compared to PS alone. In calcium ion-induced contractions, indometacin pretreatment increased CuZnSOD, GSH-Px and GR activities. These results suggest that, in addition to its COX inhibitory effects, indometacin influences the effects of PS. Therefore, it is possible that indometacin regulates diverse cell functions via its association with lipid membranes by altering micro-environments within the membranes. The above-mentioned processes appear to be partly mediated by redox processes involving ROS, lipid peroxides and antioxidant enzymes. The extent of the PS-mediated effect as different in spontaneous versus calcium ion-induced active uteri.

Different responses of mesenteric artery from normotensive and spontaneously hypertensive rats to nitric oxide and its redox congeners.

The conversion of nitric oxide (NO*) into its congeners nitrosonium (NO(+)) and nitroxyl (HNO/NO(-)) ions may have important consequences for signal transduction and physiological responses. Manganese-containing superoxide dismutase (MnSOD) may convert NO. into its redox congeners. In our current work, we have examined the mechanism of sodium nitroprusside (SNP)-induced relaxation of arteries, with or without endothelium, from both normotensive and spontaneously hypertensive (SH) rats in the absence and presence of MnSOD. SNP induced a greater degree of relaxation in normotensive than in SH rats. MnSOD antagonized SNP-induced relaxation and effect was greater in normotensive than hypertensive rats. However, MnSOD even potentiated SNP-induced relaxation in mesenteric arteries with endothelium from SH rats. Our results indicate that HNO/NO(-)-mediated relaxation is more effective in mesenteric artery smooth muscle from SH rats than from normotensive rats and that vascular dysfunction in SH rats is not solely endothelium-derived but involves changes in vascular smooth muscles.

[Relaxant effects of protamine sulfate on isolated renal arteries of normotensive and hypertensive rats]. / Relaksantni efekat protamin-sulfata na izolovanim renalnim arterijama normaotenzivnih i hipertenzivnih pacova.

INTRODUCTION: Protamine sulfate is found to have endothelium-dependent relaxing effect on isolated blood vessels. The aim of our experiments was to study relaxant effects of protamine sulfate on isolated renal arteries of both normotensive and hypertensive rats. MATERIAL AND METHODS: Experiments were performed on renal arteries, isolated from male, Wistar, spontaneously hypertensive rats (250-300 g). The adhering perivascular tissue was carefully removed from arteries which were then cut into 3-5 mm ring segments, incubated 30 min in water bath in Krebs-Ringer bicarbonate solution at 36 degrees C, and gassed with 95% O2 and 5% CO2. Each was gradually stretched to optimal tension (2 g) and isometric transducer registered mechanical contractions. Contractions of isolated blood vessels were caused by phenylephrine (10(-6) mol) and functional integrity of the endothelium was confirmed by acetylcholine (10(-5) mol) and histopathological examination. RESULTS AND DISCUSSION: Preparations were analyzed using a microscope to distinguish differences between blood vessels of normotensive and hypertensive rats. The reason for this effect of protamine is probably its stimulating effect on nitrogen-monoxide release, which might be the main reason for systemic hypotension that occurs during protamine infusion. It occurs due to activation of endothelial NO-synthesis. Our results show a better relaxant effect of protamine with normotensive, comparing to hypertensive rats, regarding to better preservation of endothelium with normotensive animals. CONCLUSION: The relaxant effect of protamine occurs due to NO release with conductance artery, which is not the case with microvessels, where this effect occurs due to endothelium-derived hyperpolarizing factor release.