APOPTOSIS IN TARGET ORGANS OF HYPERTENSION

Apoptosis or programmed cell death frequently parallels abnormalities in cell proliferation and differention. As hypertrophy/hyperplasia or remodeling occurs in organs affected by hypertension, we evaluated the degree of apoptosis in the heart, kidney, and brain in situ in geneti cally hypertensive mice and rats as well as in cultured vascular smoot h muscle cells. Apoptosis was characterized by morphological features, DNA fragmentation, and laddering as well as by terminal deoxynucleoti dyl transferase labeling of the 3' OH ends of both extracted DNA and t issue sections. The present report provides the first evidence of incr eased apoptosis in whole organs of genetically hypertensive rat and mo use strains: in the heart of spontaneously hypertensive rats (SHR) and in the heart (ventricular cardiomyocytes), kidney (inner cortex and m edulla), and brain (cortex, striatum, hippocampus, and thalamus) of sp ontaneously hypertensive mice, with a higher effect of apoptotic induc ers in cultured aortic smooth muscle cells derived from SHR. Both type s of known apoptotic processes, oligonucleosomal cleavage and large DN A fragmentation, were observed in vascular smooth muscle cells, but on ly the former appeared to be increased in SHR. This study underlines t he importance of cell death dysregulation in hypertension, reveals a n ew route for investigation of the pathogenesis of hypertension, and su ggests novel targets of therapeutic intervention.