Normotensive sodium loading in normal man: regulation of renin secretion during beta-receptor blockade.
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 beta1-receptors (beta1-RSNA), and tested the hypothesis by studying RAAS and renal excretion during slow saline loading at constant plasma sodium concentration (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 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 micromol/min; 13 +/- 2 to 55 +/- 13 micromol/min, respectively). Na+ loading did not increase plasma atrial natriuretic peptide, glomerular filtration rate (GFR by 51Cr-EDTA), MAP, or cardiac output (CO by impedance cardiography), but increased central venous pressure (CVP) by approximately 2.0 mmHg (P < 0.05). During Na+ loading, sodium excretion increased with CVP at an average slope of 7 micromol.min(-1).mmHg(-1). Concomitantly, plasma vasopressin decreased by 30-40% (P < 0.05). In conclusion, beta1-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, beta1-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 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.
Mølstrøm
Simon
S
Department of Physiology and Pharmacology, Institute of Medical Biology, University of Southern Denmark, 21 Winslowparken, Odense, DK-5000, Denmark.
Larsen
Nils H
NH
Simonsen
Jane A
JA
Washington
Remon
R
Bie
Peter
P
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D065092:Antidiuretic Hormone Receptor Antagonists; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D004039:Diet, Sodium-Restricted; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects; D009481:Neurophysins / Q000097:blood; D009638:Norepinephrine / Q000378:metabolism; D011498:Protein Precursors / Q000097:blood; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism; D012083:Renin / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012964:Sodium / Q000097:blood / Q000652:urine; D012965:Sodium Chloride / Q000008:administration & dosage*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014667:Vasopressins / Q000097:blood; D055815:Young Adult
C438657:AVP protein, human; D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D065092:Antidiuretic Hormone Receptor Antagonists; D009481:Neurophysins; D011498:Protein Precursors; D018342:Receptors, Adrenergic, beta-1; D017483:Receptors, Vasopressin; D014667:Vasopressins; D000804:Angiotensin II; D012965:Sodium Chloride; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium; D012083:Renin; D008790:Metoprolol; D009638:Norepinephrine