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In a previous study, we found that a long-term infusion of atrial natriuretic peptide (ANP) produced a sustained reduction of mean arterial pressure and peripheral vascular resistance in two-kidney, one-clip (2K-1C) hypertensive rats, whereas in control rats it had only a transient effect on cardiac output. However, plasma levels of ANP were actually 3-fold higher in normotensive than in hypertensive rats. Previous studies suggested that plasma ANP levels might modulate the vascular reactivity to the peptide. The present study examined whether the lack of chronic hemodynamic effects of ANP in control rats was due to changes in vascular reactivity to the peptide. In control rats, vascular reactivity to ANP was reduced 50% by a chronic infusion of ANP. However, in 2K-1C hypertensive rats, a long-term infusion of ANP had no effect on the vascular reactivity to ANP. The results of the present study indicate that the lack of persistent hemodynamic effects of a chronic infusion of ANP in control rats may be due to a decrease in the vascular reactivity to the peptide. The sustained hypotensive and vasodilatory effects of a long-term infusion of ANP in 2K-1C hypertensive rats are associated with no changes in the vascular reactivity to ANP.

We have previously found that chronic infusion of atrial natriuretic peptide (ANP) decreased mean arterial pressure (MAP) by 16% in two-kidney, one-clip (2K-1C) hypertensive rats, and we hypothesized that natriuresis might be modified through the pressure-natriuresis mechanism. We therefore decided to evaluate sodium balance in 2K-1C rats infused with ANP (0.5 micrograms/h for 4 days). The ANP infusion to the 2K-1C rats induced a significant decrease in MAP from 171 +/- 3 to a minimum value of 147 +/- 6 mm Hg after 2 days of treatment (p less than 0.001). Sodium excretion fell from 2,536 +/- 60 to 2,047 +/- 86 (p less than 0.001) and 2,211 +/- 96 mu Eq/24 h (p less than 0.05) by days 1 and 2 of ANP administration. Furthermore, fractional excretion of sodium intake decreased from 99.1 +/- 1.5 to 81.1 +/- 2.9 (p less than 0.001), 84.1 +/- 2.6 (p less than 0.05) and 85.9 +/- 5.15% (p less than 0.05) by days 1, 2 and 3 of ANP infusion, respectively, returning to basal values thereafter. The administration of vehicle (0.9% NaCl) did not induce any significant change in 2K-1C hypertensive rats. The infusion of either vehicle or the same dose of ANP to normotensive rats (0.5 micrograms/h, for 4 days) did not modify sodium balance throughout the experiment. These results strongly suggest that the ANP-induced decrease in MAP might be responsible for the transitory sodium retention observed in 2K-1C hypertensive rats during the administration of the peptide.

The purpose of this study was to evaluate the hemodynamic effects induced by an infusion of synthetic rat atrial natriuretic peptide (rANP, 0.5 micrograms/h iv) during 5 consecutive days in conscious normotensive and two-kidney, one-clip hypertensive (2K,1C) rats. Changes in plasma ANP (pANP) levels and plasma renin activity (PRA) were also determined. The administration of ANP in 2K,1C rats induced a significant decrease in mean arterial pressure (MAP) from 169 +/- 3 to 138 +/- 3, and 149 +/- 3 mmHg by 2 and 5 days of infusion, respectively. This hypotension was accompanied by a significant fall in cardiac index (CI) from 400 +/- 16 to 348 +/- 14 ml.min-1.kg-1 after 2 days of ANP treatment. However, CI returned to the basal levels at the third day, and a significant decrease in total peripheral resistance (TPR) was observed by 3 and 5 days of ANP infusion. The administration of the same dose of ANP in normotensive rats did not induce changes in MAP, but CI decreased (P less than 0.001) transitorily during the first 2 days and returned to control values thereafter. Basal pANP levels were significantly elevated in the hypertensive animals (176 +/- 40 pg/ml) when compared with the normotensive rats (82 +/- 10 pg/ml). The ANP infusion resulted in lower (P less than 0.05) pANP levels in hypertensive (1,017 +/- 234 pg/ml) than in normotensive rats (3,466 +/- 975 pg/ml). PRA did not change in any group during the administration of ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the present study was to determine if atrial natriuretic peptide (ANP)-induced natriuresis is dependent on increases in glomerular filtration rate (GFR). Intrarenal blood flow distribution and urinary excretion of prostaglandins were also determined during the infusion of a dose of ANP that does not induce changes in GFR and mean arterial pressure (MAP). It was found that the intrarenal infusion of ANP (8-33) at a dose of 0.05 micrograms X kg-1. min-1 in seven anesthetized dogs did not produce any change in GFR or MAP, but its natriuretic effect was similar to that obtained by a larger dose (0.3 micrograms X kg-1 X min-1, n = 5) that produces significant changes in both MAP and GFR. The natriuresis induced by the lower dose of ANP was associated with a redistribution (P less than 0.05) of renal blood flow (RBF) from the superficial to the juxtamedullary cortex and with an increase (P less than 0.05) in urinary excretion of prostaglandins E2 (PGE2) (0.8 +/- 0.2 to 2.4 +/- 1.0 ng/min) and 6-keto-F1 alpha (6-keto-PGF1 alpha) (2.8 +/- 0.6 to 5.5 +/- 1.7 ng/min). Renin secretion rate decreased from 610 +/- 165 to 279 +/- 61 ng angiotensin I/min. These results show that the natriuresis induced by ANP is not necessarily produced by an increase in GFR and is associated with a redistribution of RBF to the deep cortex and an increase in urinary excretion of PGE2 and 6-keto-PGF1 alpha.

The aim of the present study was to examine if the natriuresis induced by a dose of ANP that does not alter glomerular filtration rate (GFR) or mean arterial pressure (MAP) is accompanied by changes in renin release urinary excretion of prostaglandins and intrarenal blood flow distribution. It was found that the intrarenal infusion of ANP (8-33) at a dose of 0.05 micrograms/kg min in seven anaesthetized dogs did not produce any change in GFR or MAP, but its natriuretic effect was similar to that induced by a larger dose (0.3 micrograms/kg min, n = 5) that produces significant changes in both MAP and GFR. The natriuresis induced by the lower dose of ANP was associated with a redistribution of RBF to the deep cortical nephrons and with an increase (p less than 0.05) in urinary excretion of prostaglandins E2 and 6 keto-F1 alpha. Renin secretion rate decreased by a 54% (p less than 0.05). The role of angiotensin II (AII) suppression on the natriuresis induced by ANP was examine in another experimental group (n = 6). It was found that the infusion of ANP during fixed intrarenal levels of AII produced a natriuretic effect that was significantly lower (38%) than that produced by the infusion of ANP alone. The results of this study show that the natriuresis induced by ANP is not necessarily produced by an increase in GFR and is associated with a redistribution of RBF to the deep cortex an increase in urinary excretion of prostaglandins and a decrease of renin release. These results also suggest that the natriuretic effect of ANP is partly mediated by the intrarenal suppression of AII.

Studies showing that atrial natriuretic peptides (ANP) induce a suppression of the renin-angiotensin system suggest that there might be a modulatory influence of angiotensin II (ANG II) on the natriuretic effect of the ANP system. To evaluate this possibility we assessed, in anesthetized dogs, the net increments in fractional excretion of sodium (FENa) and lithium (FELi) produced by ANP and by the inhibition of ANG II formation with captopril. These agents were infused at separate time periods into the renal artery at a maximal level that has been shown not to alter glomerular filtration rate (GFR). ANP caused an increment in FENa of 4.0 +/- 0.2, whereas captopril caused a much smaller increase of 0.2 +/- 0.04, indicating that most of the natriuretic effect of ANP is unlikely to be solely accounted for by inhibition of ANG II. The administration of both ANP and captopril produced increases in the FELi used as a marker for proximal tubular reabsorption. An infusion of ANG II superimposed on the infusion of captopril reduced the FENa from 1.5 +/- 0.3 to 0.8 +/- 0.1. Under these conditions the administration of ANP produced an increment of 2.7 +/- 0.4 in the FENa. This increase in FENa is 32.5% less than the net increase obtained when ANP was given in the absence of ANG II, whereas under these conditions FELi remained statistically unchanged. These results suggest that the modulatory activity of ANG II on the natriuretic affect of ANP could be negligible under normal conditions.

This study was undertaken to define the changes in plasma levels of atrial natriuretic peptide (ANP) induced by hypertonic saline infusion followed by spontaneous water drinking and to determine whether these changes in ANP are correlated with changes in right atrial pressure (RAP) and plasma levels of vasopressin (AVP). Conscious dogs (n = 5) were infused with hypertonic saline (6%) at a rate of 1.4 ml/min for 4 h. Water was withheld for the first 2 h and administered ad libitum for the final 2 h. Hypertonic saline infusion induced increases (P less than 0.05) in plasma osmolality (posM), pAVP, mean arterial pressure (MAP), and RAP (1.9 +/- 0.6 to 3.1 +/- 0.7 mmHg). These changes were accompanied by an increase of pANP (68 +/- 14 to 120 +/- 33 pg/ml, P less than 0.05). Spontaneous water drinking (1,410 +/- 127 ml) returned posM and pAVP to control levels and produced a further and significant increment in RAP (150%) and pANP (100%). During the water-drinking phase MAP was not further altered, and hematocrit decreased by 11.1% (P less than 0.05). A positive linear correlation (P less than 0.001) was found between increases in RAP and pANP. The administration of an AVP vasopressor antagonist in a similar protocol, and before hypertonic saline infusion, inhibited the increase of MAP, but it did not alter the changes of posM, hematocrit, RAP, nor pANP. These results suggest that changes in the release of ANP during increases in posM and after spontaneous water drinking are predominantly controlled by changes in RAP.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of the present study was to determine if acute and chronic increases in sodium intake by isotonic saline infusion are accompanied by changes in plasma concentrations of atrial natriuretic peptide (PANP). Acute saline loading (5% body wt) over a 30-min period in seven conscious chronically instrumented dogs produced a significant increase in PANP (48 +/- 5 to 119 +/- 24 pg/ml, P less than 0.05). However, chronic and progressive increments of sodium intake from 5 to 75 to 300 meq/day for 7 days, each by isotonic saline infusion, were examined in the same group of dogs and had no significant effect on PANP. PANP's were 37 +/- 7, 39 +/- 8, and 33 +/- 5 pg/ml when sodium intake was changed from 5 to 75 to 300 meq/day, respectively. The increase of sodium intake from 5 to 75 meq/day produced decreases of plasma renin activity (PRA) (2.5 +/- 0.5 to 1.5 +/- 0.4 ng angiotensin I X ml-1 X h-1, P less than 0.05), plasma aldosterone concentration (PAC) (19.3 +/- 5.4 to 2.9 +/- 0.4 pg/ml, P less than 0.05), and urinary excretion of prostaglandin E2 (760 +/- 131 to 320 +/- 58 pg/min, P less than 0.05). Further increase of sodium intake to 300 meq/day induced decreases of PRA and PAC to undetectable levels and an increase of urinary excretion of 6-ketoprostaglandin F1 alpha (649 +/- 95 to 1,056 +/- 148 pg/min, P less than 0.05). Before the completion of the study, sodium intake was decreased from 300 to 75 meq/day.(ABSTRACT TRUNCATED AT 250 WORDS)

The natriuretic response to the intrarenal administration of atrial natriuretic factor (ANF) is accompanied by an increase in the synthesis of prostaglandins and by a redistribution of renal blood flow from the superficial to the deep cortex. This study was undertaken to define whether prostaglandins mediate the ANF-induced redistribution of renal blood flow and if prostaglandins and renal blood flow redistribution contribute to the natriuretic actions of ANF. In anesthetized dogs, the intrarenal administration of indomethacin (10 micrograms/kg/min) or the intravenous administration of meclofenamate (5 mg/kg) completely prevented the sixfold and twofold increments in urinary prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, respectively; it also abolished the redistribution of renal blood flow to the deep cortex. However, ANF induced a similar natriuresis before (from 53 +/- 17 to 281 +/- 48 microEq/min) and after (from 45 +/- 13 to 273 +/- 60 microEq/min) the administration of prostaglandin synthesis inhibitors. It is concluded that the ANF-induced redistribution of renal blood flow to the deep cortex is prostaglandin-mediated but that neither redistribution nor increased prostaglandin synthesis is an important mediator of ANF's natriuretic action.