EVIDENCE FOR ACTIVATION OF ENDOTHELIUM AND MONOCYTES IN HYPERTENSIVE RATS

We have proposed that an interaction between perivascular macrophages and endothelium via cytokines could underlie the increased risk of str oke in hypertension. Therefore, the activation of monocytes, the endot helial expression of intercellular adhesion molecule-1 (ICAM-1), and t he numbers of monocytes/macrophages in carotid arteries, as well as th e cytokine production in carotid tissue, of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto and Sprague-Dawley rats were studied. The total number of blood monocytes (890 +/- 153 cells/mm(3) , n = 10) and the number of activated (nitro blue tetrazolium-positive monocytes (220 +/- 51 cells/mm(3), n = 10) were significantly greater (P < 0.05) in SHR than in WKY rats (440 +/- 81 and 40 +/- 16 cells/mm (3), respectively, n = 10). Patchy endothelial expression of ICAM-1 wa s found in 77 +/- 9% of carotid sections from stroke-prone SHR (SHR-SP , n = 5) and in 75 +/- 7% of the sections from SHR (n = 7) but in none of the sections from the two normotensive rat strains (n = 7). The nu mber of endothelium-attached monocytes/macrophages per millimeter of i nternal elastic lamina was significantly greater in SHR-SP than in SHR [5.1 +/- 0.7 (n = 4) and 3.3 +/- 0.3 (n = 6), P < 0.05], whereas no m onocytes were found around the endothelium in either of the normotensi ve rat strains (n = 7 in each group). Incubation of the carotid arteri es with lipopolysaccharide (30-300 ng/ml) induced a concentration-depe ndent expression of mRNAs for interleukin-1 beta and release of tumor necrosis factor-alpha to a significantly greater degree in the SHR tha n in the Wistar-Kyoto rats. The results demonstrate that hypertension is associated with activation of monocytes and endothelium and an incr eased endothelial adhesion and subendothelial accumulation of monocyte s/macrophages and with an increased vascular capacity to produce cytok ines.