Apoptosis occurs in endothelial cells during hypertension-induced microvascular rarefaction

Disappearance of microvessels (microvascular rarefaction) during hypertension is a process that exacerbates the hypertensive condition, The cellular process by which the vessels disappear is not known, In the present study, we investigate the pathogenic role of cell death, specifically apoptosis, in hypertension-induced microvascular rarefaction. An established rodent one kidney/one clip (1K1C) Goldblatt model of hypertension was used, Histological and ultrastructural characteristics of apoptosis and necrosis were used to define incidence of the two types of cell death, The new method of in situ end-labeling DNA fragmentation known to occur in apoptosis was analyzed, and expression of an apoptosis-related gene, clusterin, identified using Northern blots and in situ hybridization, Microvessels in skeletal muscle were compared in 1K1C animals (n = 3 per time point) and control animals (n = 6) at experimental times after surgery up to established hypertension (1, 2, and 4 days and 1, 2, and 6 weeks), Loss of microvessels in hypertensive animals was verified, Endothelial cell apoptosis, not necrosis, was identified and was more frequent in hypertensive animals than in controls, Apoptosis of endothelial cells was found most often within 1 week after 1K1C surgery Clusterin mRNA transcripts were increased above control levels in all 1K1C treatments, but expression was not localized specifically above endothelial cells, In this instance, increased expression of clusterin in hypertensive animals may be an epiphenomenon, not directly related to the presence of apoptosis, The results demonstrate a role for apoptosis in the development of microvascular rarefaction in hypertension, The significance of this novel finding is that these results may now be used to direct site-specific anti-apoptosis therapy for treatment of structural rarefaction, at present unaffected by conventional anti-hypertensive therapies. (C) 1997 Academic Press.