RENIN AND ANGIOTENSIN-II RECEPTOR GENE-EXPRESSION IN KIDNEYS OF RENAL HYPERTENSIVE RATS

The aim of this investigation was to examine the interrelation between renal mRNA levels of renin and angiotensin II receptor type 1 (AT(1)) in a renin-dependent form of experimental hypertension. Rats were studied 4 weeks after unilateral renal artery clipping. Mean blood pressure and plasma renin activity were significantly higher in the hypertensive rats (n = 10 206+/-8 mm Hg and 72.4+/-20.9 ng . mL(-1). h(-1), respectively) than in sham-operated controls (n = 10, 136+/-3 mm Hg and 3.3+/-0.5 ng . mL(-1). h(-1), respectively). Northern blot analysis of polyA(+) RNA obtained from the kidneys of renal hypertensive rats showed increased levels of renin mRNA in the clipped kidney, whereas a decrease was observed in the unclipped kidney. Plasma renin activity was directly correlated with renin mRNA expression of the poststenotic kidney (r=.94, P<.01). AT(1) mRNA expression was lower in both kidneys of the hypertensive rats. This downregulation was specific for the AT(1A) subtype since the renal expression of the AT(1B) subtype remained normal in hypertensive rats. The downregulation of the renal AT(1A) receptor map be due to high circulating angiotensin II levels. This is supported by the significant inverse correlation r=-.71, P<.01) between plasma renin activity and AT(1A) mRNA expression measured in the clipped kidney of the hypertensive rats.