1. To elucidate the physiological and pathophysiological role of the
natriuretic peptide system in the progression of hypertensive renal disease, we examined the gene expression of
natriuretic peptide receptor subtypes,
guanylate cyclase-A (GC-A),
guanylate cyclase-B (GC-B) and clearance receptor (C receptor), in the kidney of
stroke-prone spontaneously hypertensive rats (SHRSP) at 8 and 20 weeks of age, and compared them with their gene expression in age-matched Wistar-Kyoto (WKY) rats. 2. Northern blot analyses revealed that messages for three
natriuretic peptide receptor subtypes were expressed in the kidney, and their expressions were higher in the glomeruli than in the whole kidney in each strain. 3. In 20 week old rats with established
hypertension, the glomerular concentration of GC-A
mRNA was significantly higher in SHRSP than in WKY. The concentrations of GC-B and C receptor
mRNA in the glomeruli tended to increase and decrease, respectively, but they were not statistically significant in SHRSP. 4. In 8 week old rats, the glomerular concentrations of GC-A, GC-B and C receptor
mRNA were not significantly different between SHRSP and WKY. 5. This study demonstrates that in the progression of
hypertension, the expression of GC-A, which mediates
biological actions of
natriuretic peptides, is enhanced in the kidney of SHRSP compared to that of WKY. Together with the augmented secretion of the
ligands previously revealed, altered expression of
natriuretic peptide receptor subtypes in SHRSP may have a deterrent role in the development of
hypertension and its renal complications.