Amplification by atrial natriuretic peptide of the haemodynamic and renal responses to an acute volumic stress in the rat

1. The purpose of the present study was to test the effects of synthetic at rial natriuretic peptide (ANP) on renal haemodynamics and excretory capacit ies of salt and water in the rat during an 'acute volumic stress', which wa s induced by brisk disturbances of the circulatory volume. 2. To this end, 29 anaesthetized male Wister rats were rapidly injected wit h 1 mt of 0.85% NaCl, repeated twice at 60 s intervals. The injectates cont ained no ANP(n = 5) or 1 x 0.25 (rt = 6), 3 x 0.25 (n = 6), 1 x 2.5 (n = 6) or 3 x 2.5 mu g (n = 6) ANP,added to the first injectate only (1 x) or to each injectate (3 x). Renal blood flow (RBF) was continuously measured with an electromagnetic flow transducer. 3. Renal blood how increased transiently (approximately 30 s) by approximat ely 13 % (P < 0.05) during each injection of saline without ANP. Addition o f 0.25 or 2.5 mu g ANP to the first injectate enhanced RBF by 21 and 35%, r espectively (both P < 0.05), but did not modify the time sequence. Furtherm ore, addition of 0.25 mu g ANP to the second and third injectate produced a n almost similar change in RBF at the end of each injection (Delta RBF = 20 and 17%, respectively). In contrast, the addition of 2.5 mu g ANP to the s econd and third injectate did not produce the same changes in RBF observed at the end of the first injection. The amplitude of the change in RBF was t hen similar to the increase in RBF induced by 1 mt saline without ANP. Mean arterial pressure (MAP) did not change significantly during repeated injec tions of saline alone or with addition of 0.25 mu g ANP to the first inject ate. However, MAP decreased significantly (by 5, 9 and 9 mmHg) after the in jection of 3 x 0.25, 1 x 2.5 or 3 x 2.5 mu g ANP, respectively. 4. Sodium excretion was rapidly increased from 2.600+/-0.654 to 9.330+/-1.3 22 mu mol/min after injection of 3 x 1 mt of 0.85% NaCl (P<0.05). Thereafte r, sodium excretion remained enhanced throughout the experiment, so that 70 % of the sodium load injected was recovered at the end of the experiment. A trial natriuretic peptide added to the injectates further elevated the maxi mal responses in diuresis and natriuresis induced by saline injections with out ANP (P < 0.001). A maximal effect was observed after the addition of 2. 5 mu g ANP to the first saline solution. When the amount of sodium excreted was calculated by integrating the areas under the curve of the natriuretic responses, a relationship was established as a function of the amount of A NP added to the saline solutions. It was characterized by a threshold in th e presence of 2.5 mu g ANP added to the first injectate when the integratio n period was limited to 4 min 30 s and 14 min 30 s after starting the first injection of the varying test solutions. When the integration period was e xtended until the end of the experiment (2 h), the amount of sodium excrete d in each group was further enhanced, especially after injection of 3 x 1 m L of 0.85% NaCl without ANP or with 1 x 0.25 and 3 x 0.25 mu g ANP. Differe nces in sodium excretion between groups were attenuated (P < 0.054, ANOVA). 5. In conclusion, our results demonstrate differential effects of synthetic ANP on renal vascular reactivity and excretory capacity. These effects wer e superimposed on changes induced by acute volumic stress. In particular, e ffects of saline injections on renal vascular compliance were amplified in the presence of ANP added in varying amounts to the injectates. This amplif ication was limited to 2.5 mu g ANP.