Enalapril interferes with the effect of diclofenac on leucocyte-endothelium interaction in hypertensive rats.
Nonsteroidal anti-inflammatory drugs are known to attenuate the effects of some antihypertensive agents. However, the effect these drugs have on leukocyte migration when combined with antihypertensive agents has not been studied. To investigate this effect, we treated spontaneously hypertensive rats with saline, diclofenac, enalapril, or diclofenac combined with enalapril and observed leukocyte-endothelium interaction. Blood pressure was increased by diclofenac, reduced by enalapril and reduced by the combination of the two. Diclofenac did not interfere with the blood pressure-lowering effect of enalapril. Internal spermatic fascia venules were observed using intravital microscopy. Diclofenac reduced rollers, whereas enalapril, alone or combined with diclofenac, had no significant effect on rollers. All treatments reduced adherent and migrated leukocytes and expression of endothelial intercellular adhesion molecule-1. Venular shear rate, venular diameters, number of circulating leukocytes, and post-leukotriene B4 expression of l-selectin and CD11/CD18 integrin in leukocytes were unaffected by any treatment. Expression of P-selectin was reduced by diclofenac and unaffected by enalapril, even when combined with diclofenac. Our data suggest that, although diclofenac does not interfere with the enalapril anti-hypertensive effect, enalapril interferes with the effect diclofenac has on leukocyte rolling and endothelial P-selectin expression. Involvement of reduced endothelial intercellular adhesion molecule-1 expression might explain the lower numbers of adherent and migrated leukocytes. The anti-inflammatory properties of a nonsteroidal anti-inflammatory drug could therefore be attenuated in hypertensive patients receiving an angiotensin-converting enzyme inhibitor.
Martinez
Luis Lopez
LL
Laboratory of Hypertension and Inflammation, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paolo, SP, Brazil.
Oliveira
Maria Aparecida
MA
Miguel
Ana Silvia
AS
Rastelli
Viviani Milan Ferreira
VM
Walber
José
J
Cruz
Miranda C
MC
Tostes
Rita C A
RC
Carvalho
Maria Helena Catelli
MH
Nigro
Dorothy
D
Fortes
Zuleica Bruno
ZB
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000187:drug effects; D002464:Cell Migration Inhibition; D004008:Diclofenac / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D004347:Drug Interactions; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy*; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; D004008:Diclofenac; D007975:Leukotriene B4; D004656:Enalapril