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Intravital microscopic methods were used to investigate the dose-dependent effects of bradykinin on leukocyte-endothelial cell interactions, formation of platelet-leukocyte aggregates and venular hemodynamics in rat mesentery. Results showed that the effects of bradykinin on leukocyte rolling and adhesion is highly concentration dependent. The mechanism of these effects was found to be dependent on the activation of bradykinin B2 receptors and was mediated by the formation of platelet-activating factor (PAF) and PAF-like lipids. The effects of bradykinin on venular erythrocyte velocity and blood flow were also concentration dependent.

The current density of transient outward current in ventricular rat cells with chronic diabetes mellitus is substantially smaller compared to age-matched control rats. A whole cell voltage-clamp technique is used to analyze the ionic processes associated with prolongation of cardiac action potential. The decrease in transient outward current, steady-state outward current and L-type Ca2+ current is responsible for the action potential prolongation.

Postischemic anti-inflammatory effects of bradykinin preconditioning. Am J Physiol Heart Circ Physiol 280: H441-H454, 2001.--We sought to determine the mechanisms whereby brief administration of bradykinin (bradykinin preconditioning, BK-PC) before prolonged ischemia followed by reperfusion (I/R) prevents postischemic, microvascular dysfunction. Intravital videomicroscopic approaches were used to quantify I/R-induced leukocyte/endothelial cell adhesive interactions and microvascular barrier disruption in single postcapillary venules of the rat mesentery. I/R increased the number of rolling, adherent, and emigrated leukocytes and enhanced venular albumin leakage, effects that were prevented by BK-PC. The anti-inflammatory effects of BK-PC were largely prevented by concomitant administration of a [B.sub.2]-receptor antagonist but not by coincident [B.sub.1] receptor blockade, nitric oxide (NO) synthase inhibition, or cyclooxygenase blockade. However, NO synthase blockade during reperfusion after prolonged ischemia was effective in attenuating the anti-inflammatory effects of BK-PC. Pan protein kinase C (PKC) inhibition antagonized the beneficial effects of BK-PC but only when administered during prolonged ischemia. In contrast, specific inhibition of the conventional PKC isotypes failed to alter the effectiveness of BK-PC. These results indicate that bradykinin can be used to pharmacologically precondition single mesenteric postcapillary venules to resist I/R-induced leukocyte recruitment and microvascular barrier dysfunction by a mechanism that involves [B.sub.2] receptor-dependent activation of nonconventional PKC isotypes and subsequent formation of NO. ischemic preconditioning; leukocyte adhesion; leukocyte emigration; venular albumin leakage; protein kinase C; bradykinin [B.sub.2] receptors

A study was conducted to test the hypothesis that bradykinin act to reduce ischemia-reperfusion (I/R)-induced tissue injury by preventing leukocyte recruitment and preserving microvascular barrier function. The leukocyte-endothelial cell interactions and microvascular barrier function in rat mesentery was measured using intravital video microscopic techniques. Results indicated that bradykinin reduces I/R-induced leukocyte recruitment and microvascular dysfunction through a mechanism involving bradykinin B2-receptor-dependent nitric oxide production.

Investigates whether bradykinin prevents postischemic leukocyte adhesion and emigration and attenuates microvascular barrier disruption. Average number of adherent and emigrated leukocytes determined during preischemic and reperfused conditions in mesenteries; Mean values for number of rolling leukocytes and leukocyte rolling velocity.

Objective: Exposure to anoxia has been reported to activate ATP-sensitive potassium (K+ATP) channels in isolated ventricular myocytes. We aimed to investigate the mechanisms underlying the anoxia-induced activation of K+ATP channels. Methods: Guinea pig ventricular myocytes were isolated using collagenase digestion. Action potentials and membrane currents were recorded in the whole-cell mode of patch clamp. Exposure to anoxia was performed in a semi-closed airtight chamber, which prevented the diffusion of atmospheric oxygen into anoxic perfusate. Results: Exposure to glucose-free anoxia shortened the action potential duration (APD) to less than 20% of control in 13±3 min. Subsequent reoxygenation rapidly and completely restored the APD. The time-independent large outward current which developed during anoxia was completely suppressed by reoxygenation or by the application of glibenclamide, a K+ATP channel blocker. The presence of extracellular glucose did not prevent APD shortening during anoxia, although it significantly decreased the rate of shortening. Reoxygenation-induced restoration of the APD was inhibited after a long-lasting anoxia. In addition, repeated exposures to anoxia/reoxygenation progressively impaired the recovery of APD during reoxygenation. Conclusions: Activation of K+ATP channels occurs during anoxia. The primary source of ATP that regulates the channel activity seems to be oxidative phosphorylation. ATP derived from anaerobic glycolysis (attained by the increase of extracellular glucose) was observed to partially suppress the channel activity only when oxidative phosphorylation was severely impaired during anoxia. [ABSTRACT FROM PUBLISHER]

Intravital microscopic techniques were used to examine the mechanisms underlying bradykinin-induced leukocyte/endothelial cell adhesive interactions (LECA) and venular protein leakage (VPL) in single postcapillary venules of the rat mesentery. The effects of bradykinin superfusion to increase LECA and VPL were prevented by coincident topical application of either a bradykinin-B(2) receptor antagonist, a cell-permeant superoxide dismutase (SOD) mimetic or antioxidant, or inhibitors of cytochrome P-450 epoxygenase (CYPE) or protein kinase C (PKC) but not by concomitant treatment with either SOD, a mast cell stabilizer, or inhibitors of nitric oxide synthase, cyclooxygenase, xanthine oxidase, NADPH oxidase, or platelet-activating factor. Immunoneutralizing P-selectin or intercellular adhesion molecule-1 (ICAM-1) completely prevented bradykinin-induced leukocyte adhesion and emigration but did not affect VPL. On the other hand, stabilization of F-actin with phalloidin prevented bradykinin-induced leukocyte emigration and VPL but did not alter leukocyte adhesion. These data indicate that bradykinin induces LECA in rat mesenteric venules via a B(2)-receptor-initiated, CYPE-, oxidant- and PKC-mediated, P-selectin- and ICAM-1-dependent mechanism. Bradykinin also produced VPL, an effect that was initiated by stimulation of B(2) receptors and involved CYPE and PKC activation, oxidant generation, and cytoskeletal reorganization but was independent of leukocyte adherence and emigration.