ALTERED GENE EXPRESSION OF NATRIURETIC PEPTIDE RECEPTOR SUBTYPES IN THE KIDNEY OF STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS

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.