Insulin-Induced Renin Release: Blockade by Indomethacin in the Rat

1. Since prostaglandins appear to mediate adrenergically stimulated renin release, the effect of indomethacin was examined on insulin-induced renin and catecholamine release in conscious rats. Insulin (10 units/kg subcutaneously) increased plasma renin activity from 2.8 ± 0.5 to 9.0 ± 1.1 pmol h⁻¹ ml⁻¹ (P<0.001) while also increasing plasma adrenaline, noradrenaline and the urinary excretion of prostaglandin E₂ and F_2α. Plasma potassium and glucose were reduced by 16 and 54%respectively.

2. Indomethacin (14 μmol/kg subcutaneously) reduced the urinary excretion of prostaglandin E₂ and F_2α by 67 and 54%respectively, without altering the other parameters.

3. Indomethacin inhibited insulin-induced renin release by 67%(P<0.01) and blocked the insulin-induced increases in urinary postaglandin E₂ and F_2α. The insulin-induced changes in plasma catecholamines, potassium and glucose were unaltered by indomethacin.

4. These findings suggest that renal prostaglandins mediate this form of adrenergically stimulated renin release by acting at a site distal to the β-adrenoreceptor.