Furosemide stimulates renin expression in the kidneys of salt-supplemented rats

This study was conducted to obtain information about a possible influence of salt transport by the thick ascending limb of Henle (TALH) and the macula densa on the expression of renin in the kidney. To this end, adult male rats were subcutaneously infused with furosemide (12 mg/24 h), an established inhibitor of TALH and macula densa salt transport, or with vehicle for 6 days. The animals had free access to chow, water and salt water (0.8% NaCl, 0.1% KCl) to maintain salt and water balance. Chronic furosemide treatment led to a 20-fold increase in urine flow rates and 50% increase in kidney weights, while urine osmolality decreased by 60% and body weight gain decreased by 40% in the furosemide-treated animals. Plasma renin activities increased from 2.9 +/- 0.5 ng angiotensin I h-1 ml-1 in controls to 10.6 +/- 2.2 ng angiotensin I h-1 ml-1 in furosemide-treated rats. In parallel, kidney areas immunoreactive for renin increased by 80% and the renal content of renin mRNA increased by 120% in the animals receiving furosemide. Under the assumption that the effects seen on renal renin expression were primarily due to the inhibition of TALH and macula densa function by furosemide, our findings suggest that salt transport across the TALH and macula densa exerts a negative control function not only on the secretion but also on the expression of renin in the kidney.