We evaluated the effects of pathophysiological levels of human brain natriuretic peptide (BNP), a recently identified cardiac hormone with natriuretic activity, by determining the hemodynamic and renal responses to low dose infusion (4 pmol/kg.min for 1 h, from 1500-1600 h) of human synthetic BNP in five healthy volunteers in a randomized placebo-controlled crossover study. Compared to placebo, BNP induced significant increases in effective renal plasma flow (para-aminohippurate clearance), glomerular filtration rate (creatinine clearance), urine flow rate, and sodium excretion without affecting blood pressure, heart rate, cardiac output (echocardiographic method), peripheral vascular resistance, PRA, plasma aldosterone, or plasma norepinephrine to any significant extent. Exploration of segmental sodium handling by the lithium clearance technique showed that the natriuretic effect of BNP was due to both an increase in filtered sodium load and a reduced distal sodium reabsorption. These results indicate that the high plasma BNP levels observed in disease states, such as heart failure, may contribute to the regulation of renal hemodynamics and sodium excretion.

Medication-induced nephrotoxicity is a relevant problem in older populations. Nevertheless, several areas of uncertainty remain to be explored, including the impact of nephrotoxicity on functional outcomes relevant to older patients, the reliability of currently recommended methods for diagnosing and staging AKI, the use of innovative biomarkers in such a heterogeneous population, the effectiveness of preventing strategies and treatments and their impact on functional outcomes.

1. To examine whether posture-induced changes in central volume affect brain natriuretic peptide secretion, plasma levels of human brain natriuretic peptide-32-like immunoreactivity (hBNP-32-li) were measured by radioimmunoassay in 11 healthy subjects and 20 patients with essential hypertension after 15 min supine, 15 min sitting and 15 min with the legs raised at 60°, together with plasma atrial natriuretic peptide concentration, plasma renin activity and plasma aldosterone concentration. 2. In the supine position, the plasma hBNP-32-li level was 1.57 + 0.10 fmol/ml in healthy subjects and significantly higher in hypertensive patients (2.39 +0.13 fmol/ml, P <0.001). In both groups, plasma hBNP-32-li level significantly (P <0.001) decreased when sitting (normotensive, 1.22 +0.08 fmol/ml; hypertensive, 1.85 +0.15 fmol/ml, P <0.001 versus normotensive) and increased again after leg raising (normotensive, 2.13+0.12 fmol/ml; P <0.002 versus resting; hypertensive, 2.84 + 0.16 fmol/min, P <0.001 versus resting, P <0.025 versus normotensive). 3. The plasma atrial natriuretic peptide concentration showed similar behaviour to the plasma hBNP-32-li, whereas plasma renin activity and plasma aldosterone concentration increased during sitting and decreased during leg raising in both healthy subjects and hypertensive patients, who had significantly higher plasma aldosterone levels when supine and sitting. 4. The plasma hBNP-32-li level, measured in all postural positions, was directly correlated with plasma atrial natriuretic peptide concentration (normotensive: r = 0.55, P <0.001; hypertensive: r = 0.69, P <0.001) and inversely correlated with plasma renin activity (r = −0.56, P <0.001 and r = −0.58, P <0.001). 5. We have shown that two physiological procedures, assumption of the sitting position and raising the legs to 60°, significantly affect the plasma hBNP-32-li level in healthy subjects. The response of the plasma hBNP-32-li level to postural changes is maintained in patients with essential hypertension, who have increased plasma levels of this hormone. The relevance of the observed modifications in the plasma hBNP-32-li level to the homoeostatic response to posture remains to be established.

Our data indicate that interatrial septal pacing is safe and feasible. A significant less incidence of arrhythmic episodes has been observed during follow-up. Further controlled randomized prospective studies are necessary to establish the exact role of this technique respect to conventional or multisite stimulation when patients with paroxysmal AF need to be permanently paced.