Normotensive sodium loading in conscious dogs: regulation of renin secretion during beta-receptor blockade.
Renin secretion is regulated in part by renal nerves operating through beta1-receptors of the renal juxtaglomerular cells. Slow sodium loading may decrease plasma renin concentration (PRC) and cause natriuresis at constant mean arterial blood pressure (MAP) and glomerular filtration rate (GFR). We hypothesized that in this setting, renin secretion and renin-dependent sodium excretion are controlled by via the renal nerves and therefore are eliminated or reduced by blocking the action of norepinephrine on the juxtaglomerular cells with the beta1-receptor antagonist metoprolol. This was tested in conscious dogs by infusion of NaCl (20 micromol.kg(-1).min(-1) for 180 min, NaLoad) during regular or low-sodium diet (0.03 mmol.kg(-1).day(-1), LowNa) with and without metoprolol (2 mg/kg plus 0.9 mg.kg(-1).h(-1)). Vasopressin V2 receptors were blocked by Otsuka compound OPC31260 to facilitate clearance measurements. Body fluid volume was maintained by servocontrolled fluid infusion. Metoprolol per se did not affect MAP, heart rate, or sodium excretion significantly, but reduced PRC and ANG II by 30-40%, increased plasma atrial natriuretic peptide (ANP), and tripled potassium excretion. LowNa per se increased PRC (+53%), ANG II (+93%), and aldosterone (+660%), and shifted the vasopressin function curve to the left. NaLoad elevated plasma [Na+] by 4.5% and vasopressin by threefold, but MAP and plasma ANP remained unchanged. NaLoad decreased PRC by approximately 30%, ANG II by approximately 40%, and aldosterone by approximately 60%, regardless of diet and metoprolol. The natriuretic response to NaLoad was augmented during metoprolol regardless of diet. In conclusion, PRC depended on dietary sodium and beta1-adrenergic control as expected; however, the acute sodium-driven decrease in PRC at constant MAP and GFR was unaffected by beta1-receptor blockade demonstrating that renin may be regulated without changes in MAP, GFR, or beta1-mediated effects of norepinephrine. Low-sodium diet augments vasopressin secretion, whereas ANP secretion is reduced.
Bie
Peter
P
Department of Physiology and Pharmacology, University of Southern Denmark, 21 Winslowparken, Odense, DK-5000, Denmark. pbie@health.sdu.dk
Mølstrøm
Simon
S
Wamberg
Søren
S
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D009320:Atrial Natriuretic Factor / Q000097:blood; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D004039:Diet, Sodium-Restricted; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D007262:Infusions, Intravenous; D007606:Juxtaglomerular Apparatus / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D008790:Metoprolol / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000652:urine; 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 / Q000652:urine; D012965:Sodium Chloride / Q000008:administration & dosage*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D006727:Hormone Antagonists; D018342:Receptors, Adrenergic, beta-1; D017483:Receptors, Vasopressin; D000804:Angiotensin II; C076251:mozavaptan; D012965:Sodium Chloride; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium; D012083:Renin; D008790:Metoprolol; D011188:Potassium; D009638:Norepinephrine