Intraglomerular Expression of or-Smooth Muscle Actin in Aging Mice

To determine whether chronic treatment with enalapril initiated early in life prevents glomerular injury secondary to normal aging, CF1 mice received enalapril (20 mg/L, n=10) or nifedipine (40 mg/L, n=10) in their drinking water from the time of weaning to 12 months of life. Control mice (n=10) received tap water ad libitum. Immunocytochemical detection of renin confirmed that angiotensin-converting enzyme inhibition resulted in recruitment of renin-containing cells along the preglomerular vessels. Morphometric analysis of glomeruli included assessment of glomerular diameter and the percentage of mesangial area per glomerulus. Glomerular diameter and mesangial area were higher in control mice (99.7±0.5 fim, 12.7±0.3%) than in enalapril-treated mice (88±0.8 fim, 8.6±0.6%) (P<.05). Glomerular diameter and mesangial area in the nifedipine-treated group (99.1 ±0.9 fim, A ctin is a cytoskeletal and contractile protein highly / \ conserved and widely distributed among euA. \ . karyotic cells. In addition to their role in muscle contraction, actin filaments are involved in a variety of cellular processes, including cell movement, nerve growth, tubular gland formation, movement of intestinal microvilli, cytoplasmic flows, and gastrulation. In adult mammals, six different actin isoforms have been described. Two of these actin isoforms are specific for striated muscle, including skeletal a-actin and cardiac a-actin. Two other isovariants are specific for smooth muscle and are designated aand y-smooth muscle (SM) actin. The remaining two isoforms are known as nonmuscle isoactins. These include /3and •y-nonmuscle actin. These variants predominate in nonmuscle tissues, although they can also be found in undifferentiated skeletal muscle.The terms a, /3, and y designate variants that can be distinguished by their isoelectric points. In mature vascular smooth muscle, o-SM and y-SM are the predominant isoforms.' However, the proportions of each isoform change markedly during embryonic development.--* Although several studies have examined the development of actin expression in vitro,fewer studies have been performed in vivo. We have recently shown that a-SM actin is a useful marker for the study of the ontogeny of the intrarenal vasculature.The aforementioned studies allowed us to conclude that expression of a-SM actin follows the centrifugal pattern of nephrovascular development and that during early fetal and postnatal life From the Hospital Israelita, Buenos Aires, Argentina, and the University of Virginia, Charlottesville. Reprint requests to R. Ariel Gomez, MD, Pediatric Nephrology and the Child Health Research Center, University of Virginia Health Sciences Center, MR4 Bldg, Room 2001, Charlottesville, VA 22908. 12.4±0.9%) were not different from control mice. These results demonstrate that angiotensin-converting enzyme inhibition prevents the glomerular enlargement and mesangial expansion observed during natural aging. In addition, control glomeruli expressed a-smooth muscle actin in a mesangial distribution. This effect was prevented by enalapril treatment but not by nifedipine. We conclude that long-term treatment with enalapril from early life prevents the early changes associated with glomerular injury and expression of a-smooth muscle actin in the glomerulus. a-Smooth muscle actin may participate in and serve as an early marker of the glomerular injury during the normal aging process. (Hypertension. 1994,23 [part 2]:889-893.)