Apoptosis in Kidney and the Heart of the Spontaneously Hypertensive Rats

Yoon, Sung Chul; Kim, Young Kwon; Kim, Yong Jin

Abstract

BACKGROUND: The terminal features of hypertensive target organ damage include decrease in the kidney size and increase in the heart size and wall thickness. Increased apoptosis has been known in the hypertensive nephrosclerosis and in the hypertensive heart failure. We hypothesized that apoptosis may progress by different degrees in the kidneys and heart with hypertension being sustained. To test this hypothesis we examined apoptosis in the kidneys and hearts of spontaneously hypertensive rats(SHR) of various ages. In addition, we examined histopathology of the kidneys.
METHODS
The kidneys and hearts of 19 SHR were excised at the age of 16 weeks(n=4), 20 weeks (n=6), and 32 weeks(n=9). Sprague-Dawley rats(SDR, n=6) were also sacrificed at the age of 16-24 weeks. Degree of apoptosis was evaluated semi-quantitati-vely by counting the number of apoptotic nuclei, stained by TUNEL method, per high power field(x400). Light microscopic and electron microscopic examination of the kidneys were performed.
RESULTS
1) In SHR kidneys, the number of apoptotic nuclei at the age of 16 weeks was similar to that in SDR kidneys(9.3+/- 0.5 vs. 10.2+/- 2.2, p=NS). However, the number was significantly, p<0.05, increased at the ages of 20 weeks and 32 weeks(31.5+/- 4.4 and 34.1+/- 4.0, respectively) as compared with that in SHR kidneys at the age of 16 weeks and that in SDH kidneys. 2) In SHR hearts, the number of apoptotic nuclei at the ages of 16, 20, and 32 weeks(4.0+/- 1,2, 2.0+/- 0.7, 1.9+/- 0.4, respectively) was neither changed nor different significantly from that in SDR hearts(0.70.5, p=N5), although the heart of SHR was hypertrophied at the age of 32 weeks. 3) Apoptosis was detected most frequently in the outer medulla of the kidneys in SHB. Histopathologic findings were the segmented sclerosis of glomeruli (1/25-50 glomeruli), edema, vacuolization and decreased villi of tubular epithelial cells. The older the age of SHR was, the more severe histopathologic changes were found. COMCLUSION: The sustained hypertansion caused increased apoptosis in the kidneys but no increased apoptosis in the heart of SHR during the specified ages of our study. The longer the duration of hyper- tension was, the more apoptotic cells and the more severe histopathologic changes, mainly in the tubulo-interstitial area, were found in the kidneys. The most frequent site of apoptosis was the outer medulla. It is suggested that apoptosis in the kidneys begin earlier than that in the heart in hypertensive target organ damage.