This study evaluates the relative importance of several mechanisms possibly involved in the natriuresis elicited by slow sodium loading, i.e. the renin-angiotensin-aldosterone system (RAAS), mean arterial blood pressure (MAP), glomerular filtration rate (GFR), atrial natriuretic peptide (ANP), oxytocin and nitric oxide (NO). Eight seated subjects on standardised sodium intake (30 mmol NaCl day _1 ) received isotonic saline intravenously (NaLoading: 20 mmol Na + kg _1 min _1 or ~11 ml min _1 for 240 min). NaLoading did not change MAP or GFR (by clearance of 51 Cr-EDTA). Significant natriuresis occurred within 1 h (from 9 ± 3 to 13 ± 2 mmol min _1 ). A 6-fold increase was found during the last hour of infusion as plasma renin activity, angiotensin II (ANGII) and aldosterone decreased markedly. Sodium excretion continued to increase after NaLoading. During NaLoading, plasma renin activity and ANGII were linearly related (R = 0.997) as were ANGII and aldosterone (R = 0.999). The slopes were 0.40 pM ANGII (mi.u. renin activity) _1 and 22 pM aldosterone (pM ANGII) _1. Plasma ANP and oxytocin remained unchanged, as did the urinary excretion rates of cGMP and NO metabolites (NO x ). In conclusion, sodium excretion may increase 7-fold without changes in MAP, GFR, plasma ANP, plasma oxytocin, and cGMP-and NO x excretion, but concomitant with marked decreases in circulating RAAS components. The immediate renal response to sodium excess appears to be fading of ANGII-mediated tubular sodium reabsorption. Subsequently the decrease in aldosterone may become important.

We studied the effects of 3-h infusions of ANG III, ANG-(1-7), and ANG IV in doses equimolar to physiological amounts of ANG II (3 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ), in six men on low-sodium diet (30 mmol/ day). The subjects were acutely pretreated with canrenoate and captopril to inhibit aldosterone actions and ANG II synthesis, respectively. ANG II infusion increased plasma angiotensin immunoreactivity to 53 Ϯ 6 pg/ml (ϩ490%), plasma aldosterone to 342 Ϯ 38 pg/ml (ϩ109%), and blood pressure by 27%. Glomerular filtration rate decreased by 16%. Concomitantly, clearance of endogenous lithium fell by 66%, and fractional proximal reabsorption of sodium increased from 77 to 92%; absolute proximal reabsorption rate of sodium remained constant. ANG II decreased sodium excretion by 70%, potassium excretion by 50%, and urine flow by 80%, whereas urine osmolality increased. ANG III also increased plasma aldosterone markedly (ϩ45%), however, without measurable changes in angiotensin immunoreactivity, glomerular filtration rate, or renal excretion rates. During vehicle infusion, plasma renin activity decreased markedly (ϳ700 to ϳ200 mIU/l); only ANG II enhanced this decrease. ANG-(1-7) and ANG IV did not change any of the measured variables persistently. It is concluded that 1) ANG III and ANG IV are cleared much faster from plasma than ANG II, 2) ANG II causes hypofiltration, urinary concentration, and sodium and potassium retention at constant plasma concentrations of vasopressin and atrial natriuretic peptide, and 3) a very small increase in the concentration of ANG III, undetectable by usual techniques, may increase aldosterone secretion substantially. healthy humans; angiotensin peptides; aldosterone secretion; sodium excretion THE RENIN-ANGIOTENSIN-ALDOSTERONE system (RAAS) is the single most important regulator of the sodium homeostasis. This specific role of the RAAS makes it a major determinant of extracellular fluid volume and arterial blood pressure. It has long been recognized that ANG II is the pivotal component of this system.

Background Knowledge of cardiac involvement in idiopathic inflammatory myopathies (IIM) is limited and a matter of debate with reported frequencies between 6% and 75%. Although clinically overt disease is rare, cardiac events are the major cause of death in IIM. No studies of the heart by SPECT/CT in newly diagnosed, untreated adults with IIM have been performed. Objectives To examine cardiac involvement in newly diagnosed, untreated patients with IIM by cardiac SPECT/CT imaging compared to a gender- and age- matched control group. Methods In a cross-sectional, single-centre study of 14 untreated patients newly diagnosed with IIM (polymyositis 7, dermatomyositis 4, cancer-associated myositis 2, immune-mediated necrotizing myopathy 1) and of 14 gender- and age- matched healthy controls. 99mtechnetium pyrophosphate (99mTc-PYP) SPECT/CT imaging was performed and cardiac 99mTc-PYP uptake was correlated to blood 99mTc-PYP uptake and weight-adjusted. Cardiac 99mTc-PYP uptake was reported in kBq/ml with the following ranges; low uptake (< 0 kBq/ml); normal uptake (0-12 kBq/ml); or high uptake (≥ 12 kBq/ml). Furthermore, disease activity was measured by Health Assessment Questionnaire (HAQ, range 0-3), myositis intention-to-treat activity index (MITAX, range 0-1), manual muscle test of 8 muscle groups (MMT8, range 0-80), serum levels of creatinine kinase (CK), C-reactive protein (CRP) and cardiac troponin I (TnI), a highly specific marker of myocardial injury. Also presence of circulating antinuclear antibodies (ANA) and myositis specific autoantibodies (MSA) was determined. Results The mean age of the patients was 59.5 years and 57% were women. Mean duration of disease symptoms was 2 years (range 0.1-10.1). At disease onset 14% had mild, 43% had moderate and 43% patients had severe or extremely severe myositis. At study entry mean HAQ was 1.2 (range 0.25 – 3), mean MITAX was 0.42 (range 0.17 -0.72), and mean MMT8 was 69 (range 52 – 80). Increased CRP levels was found in 6 (43%) patients and 12 (86%) had elevated levels of CK. ANA was found in 6 patients and 5 patients had one or more MSA. TnI was insignificantly increased in IIM compared to healthy controls (P < 0.05). Abnormal cardiac 99mTc-PYP uptake was observed in 7 (50%) patients and no controls (P = 0.002). Conclusions Heart involvement, as detected by the presence of abnormal cardiac 99mTc-PYP uptake on SPECT/CT imaging, is more prevalent in untreated IIM patients than in age- and gender- matched healthy controls. These findings support the notion that heart involvement in IIM patients is common and that a comprehensive heart evaluation in IIM patients at disease onset is warranted. Disclosure of Interest None Declared

Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation.

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