Normotensive sodium loading in normal man: Regulation of renin secretion during beta-receptor blockade

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 beta1-receptors (beta1-RSNA), and tested the hypothesis by studying RAAS and renal excretion during slow saline loading at constant plasma sodium con-centration (Na-loading: 12 micromol Na(+) kg(-1) min(-1) for 4 h). Normal subjects were studied on low-sodium intake with and without beta1-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 micromol min(-1); 13+/-2 to 55+/-13 micromol min(-1), respectively). Na-loading did not increase plasma atrial natri-uretic peptide (pANP), glomerular filtration rate (GFR by (51)Cr-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 micromol/min per mmHg. Concomitantly, plasma vasopressin decreased by 30-40% (p<0.05). In conclusion, beta1-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, beta1 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 beta1-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. Key words: Blood pressure, angiotensin, aldosterone, natriuresis.