Increased endothelium--monocyte interactions in salt-sensitive hypertension: effect of L-arginine.
Although adhesion of monocytes to endothelial cells is considered as one of the initial factors leading in the long term to the development of atherosclerosis, the effects of hypertension on monocyte-endothelial cell interactions are still largely unknown. Thus we evaluated whether hypertension affects adhesion of monocytes on rat carotid endothelium, and whether this adhesion may be modified by long-term treatment with L-arginine, the physiologic precursor of nitric oxide (NO). Hypertension was induced in Dahl rats using a sodium-rich diet (8%), in the absence or the presence of L-arginine (1.25 g/L in drinking water). After 1 month, the carotid arteries were isolated, opened longitudinally, and incubated in the presence of 2 x 10(6) monocytes previously rendered fluorescent by incubation with tetramethyl rhodamine isothiocyanate (TRITC), and adherent cells were counted under fluorescence microscopy. In parallel, the production of NO was evaluated in vitro in isolated aorta and isolated hearts. Hypertension markedly increased adhesion of monocytes on carotid endothelium, and this was reduced by L-arginine. Hypertension also reduced an index of NO release at the level of the aorta and the coronary circulation. This impaired release of NO was partially prevented by L-arginine. Thus hypertension was associated with an increased adhesion of monocytes, which is probably due at least in part to a decreased production of NO. The increased adhesion was partly reduced by L-arginine, possibly secondary to an increased production of NO. Such an increased adhesion of monocytes may contribute the increased cardiovascular risk in hypertension.
Artigues
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INSERM E9920, Department of Pharmacology (IFRMP 23), Rouen, University Medical School and Rouen University Hospital, France.
Richard
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Roussel
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Lallemand
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Henry
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JP
Thuillez
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D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D002339:Carotid Arteries; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D020303:Rats, Inbred Dahl; D012701:Serotonin / Q000494:pharmacology; D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016166:Free Radical Scavengers; D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine