HYPERTENSIVE RENAL DAMAGE - MODULATION EXPRESSION OF SMOOTH-MUSCLE MYOSIN HEAVY-CHAIN ISOFORMS

The aim of this study was to determine the phenotypic modulation in pr eglomerular vascular smooth muscles and glomerular cells in hypertensi on. Eight-week-old stroke-prone spontaneously hypertensive rats (SHRSP ) fed high sodium pellets (3%) were untreated or treated with a calciu m antagonist, manidipine HCl (2 mg/kg per day), for 8 weeks. The expre ssion of myosin heavy chain isoforms (MHC), SM2 (muscle-type) and SMem b (non-muscle-type) or alpha-actin was examined by the immunohistochem ical technique. In normotensive Wistar-Kyoto rats, both SM2 and alpha- actin were expressed equally in the smooth muscles of preglomerular ve ssels, and SMemb was expressed slightly in the glomerular epithelial c ells. In the SHRSP, however, the expression of SM2 and alpha-actin was significantly decreased or disappeared in the afferent arterioles, de pending on the degree of vascular damage. In damaged glomeruli, SMemb and alpha-actin were newly expressed in mesangial cells. Manidipine HC l attenuated the renal damage and restored the expression of alpha-act in in the afferent arterioles. There was a significant correlation bet ween the glomerular damage and the attenuation of SM2 expression (r=0. 87). In conclusion, phenotypic modulation of vascular smooth muscles o ccurred in hypertensive renal damage and was correlated with the glome rular damage, where the phenotypic modulation also took place in the m esangial cells. These results indicate that the phenotypic modulations revealed by the expression of myosin isoforms might play an important role in the development of hypertensive renal damage.