Microvascular responses to ischemia/reperfusion in normotensive and hypertensive rats.
The objective of the present study was to determine whether long-term arterial hypertension renders the microvasculature more vulnerable to the deleterious inflammatory responses elicited by ischemia and reperfusion (I/R). Intravital fluorescence microscopy was used to monitor leukocyte adherence and emigration, platelet-leukocyte aggregation, and albumin extravasation in mesenteric postcapillary venules of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) after 10 minutes of ischemia and subsequent reperfusion. Significant and comparable increases in leukocyte adherence/emigration and the formation of platelet aggregates were elicited by I/R in both WKY and SHR. Albumin extravasation was enhanced after I/R in SHR, but not in WKY. Monoclonal antibodies directed against the adhesion glycoproteins CD18, P-selectin, or ICAM-1 showed similar patterns of protection against the I/R-induced inflammatory responses in WKY and SHR. The enhanced albumin extravasation noted in postischemic venules of SHR was prevented by immunoneutralization of either CD18 on leukocytes or ICAM-1 on endothelial cells. These results suggest that, whereas long-term arterial hypertension does not significantly modify the leukocyte and platelet recruitment normally elicited in venules by I/R, it does result in an exaggerated albumin leakage response, which is mediated by an interaction between beta(2) (CD18) integrins on leukocytes and ICAM-1 on endothelial cells.
Kurose
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Department of Molecular Physiology, Center of Excellence in Arthritis and Rheumatism, Louisiana State University Medical Center, Shreveport, LA, USA.
Wolf
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Cerwinka
W
W
Granger
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DN
D000818:Animals; D018821:CD18 Antigens / Q000502:physiology; D003627:Data Interpretation, Statistical; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000502:physiology; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress; D019007:P-Selectin / Q000502:physiology; D010974:Platelet Aggregation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015427:Reperfusion Injury / Q000097:blood / Q000503:physiopathology*; D013997:Time Factors; D014699:Venules / Q000503:physiopathology
D018821:CD18 Antigens; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1