Peer-Reviewed Journal Details
Mandatory Fields
Chamienia AL, Johns EJ;
British Journal of Pharmacology
The interaction between atrial natriuretic peptides and angiotensin II in controlling sodium and water excretion in the rat.
Optional Fields
1. The present study was designed to determine how the natriuretic and diuretic actions of atrial natriuretic peptides were modulated by circulating angiotensin II. 2. In sodium pentobarbitone-anaesthetized rats, administration of bolus doses of atriopeptin III (1000 ng kg-1) had no effect on blood pressure, renal blood flow, or glomerular filtration rate but caused reversible increases (all P less than 0.001) in urine flow, of 53.9 +/- 14.4 microliters kg-1 min-1, absolute sodium excretion, of 13.4 +/- 2.9 mumol kg-1 min-1 and fractional sodium excretion of 3.26 +/- 0.74%. Similar effects were seen following a second dose of the atriopeptin III. 3. Following blockade of the renin-angiotensin system with captopril (900 micrograms kg-1 h-1), control levels of blood pressure and haemodynamics were unchanged but there were significant (all P less than 0.001) increases in urine flow, from 39.96 +/- 5.05 to 88.70 +/- 8.41 microliters kg-1 min-1, absolute sodium excretion, from 8.35 +/- 1.08 to 21.62 +/- 1.62 mumol kg-1 min-1 and fractional sodium excretion, from 3.82 +/- 0.23 to 5.34 +/- 0.32%. Under these conditions, atriopeptin III-induced increases in urine flow (110.2 +/- 8.7 versus 43.9 +/- 6.2 microliters kg-1 min-1) absolute (24.0 +/- 1.8 versus 9.3 +/- 1.2 mumol kg-1 min-1) and fractional (5.16 +/- 0.24 versus 2.08 +/- 0.33%) sodium excretions were significantly (P less than 0.001) greater.4. In another group of rats given captopril, angiotensin II at ongkg-1 min1 was also infused; this had no effect on blood pressure or renal haemodynamics, but partially restored basal levels of sodium and water excretion to those obtained before captopril. Atriopeptin III reversibly increased urine flow and absolute sodium excretion to the same degree as that obtained without captopril, but fractional sodium excretion was significantly larger than that obtained in the absence of captopril. In rats infused with angiotensin II at 15ngkg-1min1' together with the captopril the basal levels of fluid output were unchanged, while the magnitudes of the urine flow and sodium excretory responses to atriopeptin III were identical to those obtained before captopril and angiotensin II.5. In animals subjected to two weeks of a low-sodium diet, atriopeptin III reversibly increased urine flow, absolute and fractional sodium excretions by between 53% and 74%; these responses were significantly (P < 0.001) smaller than those obtained in sodium replete rats. Administration of atriopeptin III, to low sodium diet rats given captopril, induced excretory responses which were significantly larger than those obtained in the absence of captopril. 6. The findings of this investigation demonstrate that in acute situations, angiotensin II exerts an important modulatory influence on the natriuretic potency of the atrial peptides by attenuating their action on the kidney. Long-term activation of the renin-angiotensin system depresses the renal excretory responses to atrial natriuretic peptides but suppression of angiotensin II production only partially restores the responsiveness of the kidney.
Grant Details