Submitted on September 8, 2008
Revised on December 1, 2008
Accepted on December 1, 2008
Normotensive sodium loading in normal man: Regulation of renin secretion during beta-receptor blockade
Simon Mølstrøm1, Nils Heden Larsen2, Jane Angel Simonsen2, Remon Washington, and Peter Bie1*
1 University of Southern Denmark, Institute of Medical Biology
2 Odense University Hospital
* To whom correspondence should be addressed. E-mail: pbie{at}health.sdu.dk.
Saline administration may change renin system (RAAS) activity and sodium excretion at constant mean arterial pressure (MAP). We hypothesized that such responses are elicited mainly by renal sympathetic nerve activity by 
1-receptors (1-RSNA), and tested the hypothesis by studying RAAS and renal excretion during slow saline loading at constant plasma sodium con-centration (Na-loading: 12 µmol Na+ kg-1 min-1 for 4 h). Normal subjects were studied on low-sodium intake with and without 1-adrenergic blockade by metoprolol. Metoprolol per se reduced RAAS activity as expected. Na-loading decreased plasma renin (PRC) by 1/3, AngII by 1/2, and aldosterone (pAldo) by 2/3, (all p<0.05); surprisingly, these changes were found without as well as during acute metoprolol administration. Concomitantly, sodium excretion increased indistinguishably with and without metoprolol (16±2 to 71±14 µmol min-1; 13±2 to 55±13 µmol min-1, respectively). Na-loading did not increase plasma atrial natri-uretic peptide (pANP), glomerular filtration rate (GFR by 51Cr-EDTA), MAP, or cardiac output (CO by impedance cardiography), but increased central venous pressure (CVP) by approxi-mately 2.0 mmHg (p<0.05). During Na-loading, sodium excretion increased with CVP at an av-erage slope of 7 µmol/min per mmHg. Concomitantly, plasma vasopressin decreased by 30-40% (p<0.05). In conclusion, 1-adrenoceptor blockade affects neither the acute saline-mediated deacti-vation of RAAS nor the associated natriuretic response, and the RAAS response to modest saline loading seems independent of changes in MAP, CO, GFR, 1 mediated effects of norepineph-rine, and ANP. Unexpectedly, the results do not allow assessment of the relative importance of RAAS dependent and independent regulation of renal sodium excretion. The results are com-patible with the notion that at constant arterial pressure, a volume-receptor elicited reduction in RSNA, via receptors other than 1-adrenoceptors, decreases renal tubular sodium reabsorption proximal to the macula densa leading to increased NaCl concentration at the macula densa and subsequent inhibition of renin secretion.
