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

作者：Molstrom Simon; Larsen Nils H; Simonsen Jane A; Washington Remon; Bie Peter^*

来源：American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2009, 296(2): R436-R445.

DOI：10.1152/ajpregu.90754.2008

• blood pressure
• angiotensin
• aldosterone
• natriuresis
• sodium balance

Molstrom S, Larsen NH, Simonsen JA, Washington R, Bie P. Normotensive sodium loading in normal man: regulation of renin secretion during beta-receptor blockade. Am J Physiol Regul Integr Comp Physiol 296: R436-R445, 2009. First published December 10, 2008; doi: 10.1152/ajpregu.90754.2008.-Saline administration may change renin-angiotensin-aldosterone 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 beta(1)-receptors (beta(1)-RSNA), and tested the hypothesis by studying RAAS and renal excretion during slow saline loading at constant plasma sodium concentration (Na(+) loading; 12 mu mol Na(+).kg(-1).min(-1) for 4 h). Normal subjects were studied on low-sodium intake with and without beta(1)-adrenergic blockade by metoprolol. Metoprolol per se reduced RAAS activity as expected. Na(+) loading decreased plasma renin concentration (PRC) by one-third, plasma ANG II by one-half, and plasma aldosterone by two-thirds (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 mu mol/min; 13 +/- 2 to 55 +/- 13 mu mol/min, respectively). Na(+) loading did not increase plasma atrial natriuretic peptide, glomerular filtration rate (GFR by (51)Cr-EDTA), MAP, or cardiac output (CO by impedance cardiography), but increased central venous pressure (CVP) by similar to 2.0 mmHg (P < 0.05). During Na(+) loading, sodium excretion increased with CVP at an average slope of 7 mu mol.min(-1).mmHg(-1). Concomitantly, plasma vasopressin decreased by 30-40% (P < 0.05). In conclusion, beta(1)-adrenoceptor blockade affects neither the acute saline-mediated deactivation of RAAS nor the associated natriuretic response, and the RAAS response to modest saline loading seems independent of changes in MAP, CO, GFR, beta(1)-mediated effects of norepinephrine, 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 compatible with the notion that at constant arterial pressure, a volume receptor elicited reduction in RSNA via receptors other than beta(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.

• 出版日期2009-2
• 单位河北医科大学