MONOCYTE CHEMOATTRACTANT PROTEIN-1 EXPRESSION IN AORTIC TISSUES OF HYPERTENSIVE RATS

Monocyte chemoattractant protein-1 (MCP-1), a potent monocyte chemoatt ractant synthesized by vascular cells and monocytes, has been proposed to be an important mediator of inflammatory responses in the arterial vasculature. It was recently demonstrated that hypertension is associ ated with an inflammatory response in the arterial wall. To determine the effect of hypertension on arterial MCP-1 expression, we induced hy pertension in Sprague-Dawley rats by infusing angiotensin II (0.75 mg . kg(-1) . d(-1) SC) for 7 days. Using Northern blot analysis, we dete cted a 3.6-fold increase in MCP-1 mRNA in the aortas of hypertensive r ats. When we normalized blood pressure in angiotensin II-treated rats through oral administration of the nonspecific vasodilator hydralazine (15 mg . kg(-1) . d(-1)), aortic MCP-1 mRNA expression was significan tly reduced. Similar results were obtained with a norepinephrine model of hypertension. Taken together, these data suggest that mechanical f actors may be responsible in part for the upregulation of expression. Consistent with this interpretation, we found that cultured rat aortic vascular smooth muscle cells exposed to mechanical strain (20% peak d eformation at 1 Hz) exhibited a marked increase in MCP-1 expression, s uggesting the hemodynamic strain imparted onto arterial cells in hyper tension is an important stimulus underlying this phenomenon. These res ults provide important insights into the in vivo regulation of MCP-1 a nd have potential implications for understanding the influence of hype rtension on atherosclerosis.