Intrarenal angiotensin II inhibition influences the actions of atrial natriuretic peptide

1. We previously found that kidneys isolated from salt-restricted rats were refractory to atrial natriuretic peptide compared with kidneys from salt-loaded rats. Because the intrarenal tissue renin-angiotensin system may modulate renal responses to atrial natriuretic peptide, we examined the effect of dietary NaCl loading on the responses of isolated perfused kidneys from normal rats to atrial natriuretic peptide, before and after the addition of angiotensin II receptor antagonists or angiotensin I converting enzyme inhibitors to the perfusate. 2. Atrial natriuretic peptide increased the glomerular filtration rate and sodium excretion of kidneys from NaCl-loaded rats. The addition of angiotensin receptor antagonists or converting enzyme inhibitors partially reversed the increments in glomerular filtration rate but not the increments in sodium excretion, leading to an increased fractional sodium excretion. In the absence of atrial natriuretic peptide, these agents did not affect glomerular filtration or sodium excretion. Kidneys from NaCl-restricted rats did not respond to atrial natriuretic peptide or to the inhibitors and antagonists, either separately or in combination. 3. After NaCl loading, the intrarenal renin-angiotensin system may augment the glomerular response to atrial natriuretic peptide while simultaneously inhibiting the natriuretic response to atrial natriuretic peptide. However, activation of the intrarenal renin-angiotensin system is not responsible for the refractoriness of kidneys from salt-restricted rats to atrial natriuretic peptide.