Inhibitory effects of antihypertensive drugs on mesangial cell proliferation after anti-thymocyte serum (ATS)-induced mesangiolysis in spontaneously hypertensive rats.

The effects of antihypertensive drugs on mesangial cell proliferation were studied in spontaneously hypertensive rats (SHR) with anti-thymocyte serum (ATS)-induced glomerulo-nephritis. Rats were treated with either enalapril (Group 1), nifedipine (Group 2), or reserpine + hydrochlorothiazide + hydralazine (Group 3), or were untreated (Group 4). The animals were sacrificed 2, 4 and 7 days after ATS injection and the glomerular cell number and degree of mesangial area expansion were examined. A marked, similar decrease in glomerular nuclear cell number (NC) due to severe mesangiolysis was observed in all of the groups on day 2. Thereafter, an increase in NC reflecting mesangial cell proliferation after mesangiolysis occurred in Group 4 on days 4 and 7. In Group 1 and 2, the NC was significantly smaller than that in Group 4 on days 4 and 7, indicating suppression of mesangial cell proliferation. In Group 3, however, the number of NCs did not differ from that in Group 4 on days 4 and 7, indicating a lack of such suppression by conventional antihypertensive drugs. The degree of mesangial area expansion (MS) showed the same pattern as mesangial cell proliferation. That is, the rapid increases in MS seen in Group 4 on days 4 and 7 were apparently suppressed in Groups 1 and 2, but not in Group 3. Our in vivo observations that both an angiotensin converting enzyme (ACE) inhibitor and a calcium channel blocker suppress mesangial cell proliferation and mesangial area expansion suggest that these agents have practical implications in the treatment of mesangial proliferative glomerular diseases through the suppression of excess mesangial cell proliferation.