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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.