Lowering of the perfusion pressure from 100 mmHg to 40 mmHg resulted in an increase of average renin secretion rates from 3.5+/-0.5 to 79+/-12 ng AngI/h per min per g under control conditions (n = 8), and to 171+/-20 ng AngI / h per min per g in the presence of 10 mumol / liter acetylcholine (n = 3). The rise of renin secretion in response to a reduction of the renal artery pressure was markedly attenuated with inhibitors of EDRF formation such as N(G)-nitro-L-arginine (100 mumol / liter) and related compounds. During inhibition of EDRF formation, addition of sodium nitroprusside (10 mumol / liter) increased mean perfusate flow rates from 12.0+/-0.5 to 23.0+/-2.0 ml / min per g and average renin secretion rates from 2.0+/-0.5 to 18.0+/-1.5 ng AngI / h per min per g at 100 mmHg (n = 5). Lowering of the perfusion pressure from 100 mmHg to 40 mmHg under those conditions increased average renin secretion rates to 220+/-14 ng AngI / h per min per g (n = 5).

Taken together, our findings suggest that EDRF and related activators of soluble guanylate cyclase stimulate renin secretion from isolated kidneys, predominantly at lower perfusion pressure. Moreover, pressure control of renin secretion appears to require the tonical stimulation by intrarenal EDRF.