Hydralazine reduces leukocyte migration through different mechanisms in spontaneously hypertensive and normotensive rats.
In addition to reducing blood pressure, hydralazine can reduce the production of inflammatory cytokines and reduce the expression of leukocyte adhesion molecules. Differences in leukocyte behavior and leukocyte adhesion molecule expression in spontaneously hypertensive rats (SHR) compared to normotensive rats have been reported. However, whether hydralazine can reduce leukocyte migration in vivo in hypertension and in normotension remains unknown. To address this question, male SHR and Wistar rats were treated for 15 days with hydralazine at a dose of ~3.5 mg/kg or ~14 mg/kg in their drinking water. The numbers of rollers and adherent and migrated cells were determined by direct vital microscopy, and blood pressure was assessed by tail plethysmography. In addition, following treatment with the higher dose, immunohistochemistry was used to measure the expression of intercellular adhesion molecule-1 (ICAM-1), P-selectin, and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in endothelial cells, while flow cytometry was used to evaluate the expression of leukocyte CD18 and L-selectin. Hydralazine reduced leukocyte adherence and migration in SHR either at the higher, that reduced blood pressure levels, or lower dose, which did not reduce it. Reduced ICAM-1 expression might be involved in the reduced migration observed in SHR. In Wistar rats, only at the higher dose hydralazine reduced blood pressure levels and leukocyte migration. Reduced P-selectin expression might be involved. We therefore conclude that hydralazine reduces leukocyte migration by different mechanisms in SHR and Wistar rats, specifically by reducing ICAM-1 expression in the former and P-selectin expression in the latter.
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Stephen F
SF
Rodrigues
Maria A
MA
de Oliveira
Rosangela A
RA
dos Santos
Antonio G
AG
Soares
Rita
R
de Cássia Tostes
Maria Helena C
MH
Carvalho
Zuleica B
ZB
Fortes
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D006830:Hydralazine / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D007958:Leukocyte Count; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D018715:Microscopy, Video; D019007:P-Selectin / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D010991:Plethysmography; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D006830:Hydralazine