Contribution of pressure natriuresis to control of total body sodium: balance studies in freely moving dogs

Abstract

1. This study aims at determining whether elevation of renal perfusion pressure (RPP) may correct for increased total body sodium (TBS), via pressure natriuresis. 2. Freely moving dogs were studied on four consecutive days. During day 1, low-dose angiotensin II and aldosterone were infused. Pressure natriuresis was prevented by servo-controlling RPP to 20 % below the control level. Sodium and water retention increased TBS and total body water. Mean arterial blood pressure rose by approximately 25 mmHg. 3. In protocol 1, infusions and control of RPP were maintained over three more days. Sodium was retained on all days, resulting in a continuous increase in TBS. 4. In protocol 2, control of RPP was stopped after day 1. Thus, pressure natriuresis could exert its effect beginning with day 2. Angiotensin II and aldosterone infusions were continued. This prevented the effects of endogenous suppression of the renin-angiotensin-aldosterone system (RAAS), which is caused by increased TBS. No further sodium retention occurred, i.e. TBS remained at the elevated level gained on day 1. 5. In protocol 3, control of RPP and the infusions were stopped. Thus, pressure natriuresis and RAAS suppression could exert their combined effects. Sodium excretion exceeded sodium intake on day 2. Control level of TBS was regained within 24 h. 6. It was concluded that when RPP is considerably elevated, pressure natriuresis prevents further increase of TBS in the face of elevated angiotensin II and aldosterone levels. However, pressure natriuresis does not suffice to restore TBS to control. This requires additional endogenous suppression of RAAS.

Figure 1. Impact of pressure natriuresis on urinary Na⁺ excretion

Upper panels depict 24 h mean values of systemic arterial pressure (MABP) and renal perfusion pressure (RPP), as obtained by 1440 1 min values per dog and per 24 h period that lasted from 08:00 to 08:00 the following day. Lower panels depict 24 h urinary excretion of Na⁺ (U_NaV) as a percentage of daily Na⁺ intake. Values are means ± s.e.m. Dotted horizontal bars represent control group (means ± s.e.m.). Reduction of RPP plus ‘clamping’ of RAAS (low-dose angiotensin II and aldosterone infusions), as applied on day 1 of protocols 1, 2 and 3, reduces Na⁺ excretion markedly and increases 24 h mean of MABP by ∼25 mmHg. Continuation of these conditions for a further 3 days (protocol 1) results in ongoing reduction of Na⁺ excretion and continued increase of MABP. With cessation of RPP reduction at the end of day 1 (protocols 2 and 3), RPP immediately increases towards the elevated MABP (RPP = MABP), and hence pressure natriuresis can exert its effect. With continued RAAS ‘clamping’ (protocol 2), Na⁺ excretion regains control values, and MABP remains on the elevated level gained on day 1. With cessation of RAAS ‘clamping’ (protocol 3), Na⁺ excretion doubles as compared to control values (day 2), and MABP regains control level. * Significant vs. control; ⁺ significant vs. protocol 1, § significant vs. protocol 2; ¹ significant vs. day 1, ² significant vs. day 2, ³ significant vs. day 3, within the respective protocol. For statistics see Methods.

Figure 2. Contribution of pressure natriuresis to control of total body sodium

Changes of total body sodium (ΔTBS, obtained by cumulative Na⁺ balances) are shown. Values are means ± s.e.m. (for points with missing error bar, s.e.m. smaller than symbol size). For statistics see Methods; for significance symbols see Legend of Fig. 1. Reduction of RPP plus ‘clamping’ of RAAS (low-dose angiotensin II and aldosterone infusions), as applied on day 1 of protocols 1, 2 and 3, increases TBS by ∼4.4 mmol Na⁺ (kg body wt)⁻¹. Continuation of these conditions for a further 3 days (protocol 1) results in ongoing increase of TBS. With cessation of RPP reduction at the end of day 1 (protocols 2 and 3), RPP immediately increases toward the elevated MABP, and hence pressure natriuresis can exert its effect. With continued RAAS ‘clamping’ (protocol 2), TBS does not further increase, yet remains on the elevated level gained on day 1. TBS returns to control level only when RAAS ‘clamping’ is also stopped (protocol 3).