Local carbachol application induces oral microvascular recruitment and improves gastric tissue oxygenation during hemorrhagic shock in dogs.

Introduction: Hemorrhagic shock is characterized by derangements of the gastrointestinal microcirculation. Topical therapy with nitroglycerine or iloprost improves gastric tissue oxygenation but not regional perfusion, probably due to precapillary adrenergic innervation. Therefore, this study was designed to investigate the local effect of the parasympathomimetic carbachol alone and in combination with either nitroglycerine or iloprost on gastric and oral microcirculation during hemorrhagic shock. Methods: In a cross-over design five female foxhounds were repeatedly randomized into six experimental groups. Carbachol, or carbachol in combination with either nitroglycerine or iloprost were applied topically to the oral and gastric mucosa. Saline, nitroglycerine, or iloprost application alone served as control groups. Then, a fixed-volume hemorrhage was induced by arterial blood withdrawal followed by blood retransfusion after 1h of shock. Gastric and oral microcirculation was determined using reflectance spectrophotometry and laser Doppler flowmetry. Oral microcirculation was visualized with videomicroscopy. Statistics: 2-way-ANOVA for repeated measurements and Bonferroni post-hoc analysis (mean ± SEM; p < 0.05). Results: The induction of hemorrhage led to a decrease of gastric and oral tissue oxygenation, that was ameliorated by local carbachol and nitroglycerine application at the gastric mucosa. The sole use of local iloprost did not improve gastric tissue oxygenation but could be supplemented by local carbachol treatment. Adding carbachol to nitroglycerine did not further increase gastric tissue oxygenation. Gastric microvascular blood flow remained unchanged in all experimental groups. Oral microvascular blood flow, microvascular flow index and total vessel density decreased during shock. Local carbachol supply improved oral vessel density during shock and oral microvascular flow index in the late course of hemorrhage. Conclusion: The specific effect of shifting the autonomous balance by local carbachol treatment on microcirculatory variables varies between parts of the gastrointestinal tract. Contrary to our expectations, the improvement of gastric tissue oxygenation by local carbachol or nitroglycerine application was not related to increased microvascular perfusion. When carbachol is used in combination with local vasodilators, the additional effect on gastric tissue oxygenation depends on the specific drug combination. Therefore, modulation of tissue oxygen consumption, mitochondrial function or alterations in regional blood flow distribution should be investigated.

Relaxant effects of a hydroalcoholic extract of Ruta graveolens on isolated rat tracheal rings

BACKGROUND: Ruta graveolens L. (R. graveolens) is a medicinal plant employed in non-traditional medicines that has various therapeutic properties, including anthelmintic, and vasodilatory actions, among others. We evaluated the trachea-relaxant effects of hydroalcoholic extract of R. graveolens against potassium chloride (KCl)- and carbachol-induced contraction of rat tracheal rings in an isolated organ bath. RESULTS: The results showed that the airway smooth muscle contraction induced by the depolarizing agent (KCl) and cholinergic agonist (carbachol) was markedly reduced by R. graveolens in a concentration-dependent manner, with maximum values of 109 ± 7.9 % and 118 ± 2.6 %, respectively (changes in tension expressed as positive percentages of change in proportion to maximum contraction), at the concentration of 45 µg/mL (half-maximal inhibitory concentration IC50: 35.5 µg/mL and 27.8 µg/mL for KCl- and carbachol-induced contraction, respectively). Additionally, the presence of R. graveolens produced rightward parallel displacement of carbachol dose-response curves and reduced over 35 % of the maximum smooth muscle contraction. CONCLUSIONS: The hydroalcoholic extract of R. graveolens exhibited relaxant activity on rat tracheal rings. The results suggest that the trachea-relaxant effect is mediated by a non-competitive antagonistic mechanism. More detailed studies are needed to identify the target of the inhibition, and to determine more precisely the pharmacological mechanisms involved in the observed biological effects.

Effects of the chronic ingestion of an infusion of Ruta chalepensis on the vasomotor responses of rat aortic rings / Efectos de la ingestión crónica de una infusión de Ruta chalepensis sobre las respuestas vasomotoras de anillos de aorta de rata

Ruta chalepensis, is used, in traditional medicine, as emmenagogue, abortive, and analgesic. We analyzed, in male Wistar rats, the effects of the chronic intake of an infusion of Ruta chalepensis (20 g/L) on the vasomotor responses of, either intact or endothelium-denuded aortic rings, to phenylephrine or carbachol. Only in rings with endothelium significant effects were observed. The infusion induced a leftward shift of the concentration-response curve to phenylephrine and an increase in maximal tension development. These effects were abolished by indomethacin. In these rings, inhibiting the synthesis of nitric oxide, in the presence of indomethacin, induced a leftward shift of the concentration response curve to phenylephrine, as well as an increase in maximal tension. These results suggest that the chronic ingestion of a Ruta chalepensis infusion induces an endothelium dependent increase in the synthesis/release of cyclooxygenase-dependent vasoconstrictor prostanoids, and an increase in the basal synthesis/release of nitric oxide.

Ruta chalepensis se utiliza en la medicina tradicional como emenagogo, abortivo y analgésico. Se analizaron, en ratas Wistar macho, los efectos de la ingesta crónica de una infusión de Ruta chalepensis (20 g /L), sobre las respuestas vasomotoras de anillos de aorta con y sin endotelio, a la fenilefrina o al carbacol Se observaron efectos significativos sólo en anillos con endotelio. La infusión indujo un desplazamiento a la izquierda de la curva de concentración-respuesta a fenilefrina y un incremento en la tensión máxima desarrollada. Estos efectos fueron abolidos por la indometacina. La inhibición de la síntesis de óxido nítrico, en presencia de indometacina, produjo un desplazamiento a la izquierda de la curva de concentración-respuesta a la fenilefrina, así como un incremento en la tensión máxima. Estos resultados sugieren que la ingesta crónica de una infusión de Ruta chalepensis induce un incremento en la síntesis/liberación de prostanoides vasoconstrictores dependientes de la ciclooxigenasa y un aumento en la síntesis /liberación basal de óxido nítrico.

Electroacupuncture ameliorates experimental colitis induced by acetic acid in rat

The effect of electroacupuncture (EA) on experimental colitis was investigated in Sprague-Dawley rats. Colitis was induced by intracolonic instillation of 4% acetic acid. EA (2 Hz, 0.05 ms, 2 V for 20min) was applied to bilateral Hoku (LI-4) and Zusanli (ST-36) on 12 hrs and 36 hrs after induction of colitis. EA-treatment significantly reduced the macroscopic damage and the myeloperoxidase activity of colonic samples at 3 days post-induction of colitis. Colitic colon showed a decreased in vitro motility. However, colonic motility of EAtreated group was not significantly different from that of normal group. The anti-inflammatory effect of EA was not inhibited by a glucocorticoid receptor antagonist, RU-486, but suppressed by a beta-adrenoceptor antagonist, propranonol. These results suggest that EA-treatment has a beneficial effect on colitis, and its anti-inflammatory effect is mediated by beta-adrenoceptor activation but not by endogenous glucocorticoiddependent mechanism.

Inhibition of gastric acid secretion by cholinergic stimulation of the lateral hypopthalamic area

Cholinergic stimulation of the lateral hypothalamic area with carbachol (1 microng in 1 micronl) markedly inhibited gastric acid secretion in the anesthetized rat. Inhibition was bloced by prior microinjection of atropine (4 microng/micronl) into the same brain area and was accompanied by an increased soldium content in the stomach. Muscarinic receptor mediated cholinergic inhibitory influence of the hypothalamus on gastric acid secretion is suggested by these results

Interaction between cholinergic and opiate receptors of the lateral hypothalamus in the control of renal excretion in rats

The present study was carried out to investigate the participation and interaction between cholinergic and opiate receptors of the lateral hypothalamus (LH) in the regulation of Na+, K+ and water excretion. Malew Holtzman rats were implanted with chronic cerebral cannulas into the LH. Urine was collected over a period of 2h after injection of carbachol, FK-33824 + carbachol or naloxone + carbachol into the LH. Carbachol (8nmol) reduced urinary volume and increased Na + excretion. Previous injection of FK-333824(100ng) into the LH increased the antidiuretic effect of carbachol, but blocked the increase in Na+ excretion and decreased K+ excretion. Naloxone. Naloxone (10microng) produced no changes in the effect of carbacho9l on renal excretion. These data show an inhibitory effect of opiate receptors on the changes in urinary Na+ and K+ excretion that are induced by chronergic stimulation of the LH in rats, and a potentiating effect on antidiuresis

Functional characteristics (EEG) of the thalamo-telencephalic projections of toads

Electrical or chemical (carbachol) stimulation of the dorsal thalamus of anesthetized and conscious toads induced synchronization (increased number of spindles and increased amplitude of the waves) in the electric tracing (EEG) of the telencephalon. This alteration was accompanied by mydriasis and greater behavioral alert in conscious animals. No recruitment response was observed in anesthetized toads. The present findings were compared to those obtained by stimulating the nonspecific thalamus of mmmals and reptiles. Even though the data available at present do not demonstrate the existence of a system with the morphological characteristics of the reticulo-thalamo-cortical system of mammals in anurans, the functional data presented here suggest this possibility