The Role of Endothelial Cells in Hypertensive Vascular Diseases

Abstract

We studied ultrastructurally cerebral perforating arteries in 60 stroke-prone spontaneously hypertensive rats (SHRSP), which were sequentially killed at 4-52 weeks of age before showing symptoms of stroke. Another 24 SHRSP were killed soon after they showed symptoms of cerebral infarction. The initial vascular lesions included focal cytoplasmic necrosis in the outer layers of the media. This change progressed to widespread medial necrosis with time although endothelial cells were well-preserved. The adherence of monocytes to the endothelium, having advanced medial damages, triggered the accumulation of the plasma components in the arterial wall. The accumulation thickened the wall, narrowed the lumen and resulted in arterial occlusion. These results suggest that the monocytes may affect the endothelium, disturbing the so-called blood-brain barrier to proteins.
Furthermore we measured the blood pressure and histologically examined the brains, hearts, and kidneys in normotensive WKY and SHRSP rats fed on a diet containing L-N-nitroarginine (L-NNA: EDRF inhibitor). In addition we examined L-NNA-treated SHRSP, the blood pressure of which was lowered using hydralazine. Moreover we examined Goldblatt's renal hypertensive rats, which were of a different type from those resulting from the L-NNA treatment. Both WKY and SHRSP rats fed on a diet containing L-NNA suffered from hypertension and cerebral infarctions in a dose-dependent manner. Cerebral infarctions occurred whether or not SHRSP rats were treated with an antihypertensive agent when they were fed a high dosage of L-NNA. In contrast there were no cerebral infarctions in Goldblatt's renal hypertensive rats, although they suffered from advanced hypertension. The data indicate that the inhibition of EDRE injures the vessel walls and encourages platelet adhesion to the damaged areas. The adhering platelets narrow the lumen with resultant thrombotic occlusions.