Abstract |
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(2)-receptor antagonist but not by coincident B(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(2) receptor-dependent activation of nonconventional PKC isotypes and subsequent formation of NO.
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Authors | S Shigematsu, S Ishida, D C Gute, R J Korthuis |
Journal | American journal of physiology. Heart and circulatory physiology
(Am J Physiol Heart Circ Physiol)
Vol. 280
Issue 1
Pg. H441-54
(Jan 2001)
ISSN: 0363-6135 [Print] United States |
PMID | 11123262
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anti-Inflammatory Agents
- Bradykinin Receptor Antagonists
- Enzyme Inhibitors
- Nitrates
- Nitrites
- omega-N-Methylarginine
- icatibant
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type III
- Nos3 protein, rat
- Protein Kinase C
- Bradykinin
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Topics |
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- Bradykinin
(analogs & derivatives, pharmacology, physiology)
- Bradykinin Receptor Antagonists
- Capillaries
- Cell Adhesion
- Chemotaxis, Leukocyte
- Enzyme Inhibitors
(pharmacology)
- Ischemic Preconditioning
- Leukocytes
(physiology)
- Male
- Mesentery
(metabolism)
- Nitrates
(blood)
- Nitric Oxide Synthase
(antagonists & inhibitors)
- Nitric Oxide Synthase Type III
- Nitrites
(blood)
- Protein Kinase C
(antagonists & inhibitors)
- Rats
- Rats, Sprague-Dawley
- Reperfusion Injury
(metabolism, pathology, physiopathology)
- omega-N-Methylarginine
(pharmacology)
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