Normotensive sodium loading in conscious dogs: regulation of renin secretion during β-receptor blockade

Bie P, Molstrom S, Wamberg S. Normotensive sodium loading in conscious dogs: regulation of renin secretion during beta-receptor blockade. Am J Physiol Regul Integr Comp Physiol 296: R428-R435, 2009. First published December 10, 2008; doi:10.1152/ajpregu.90753.2008.-Renin secretion is regulated in part by renal nerves operating through beta(1)-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 beta(1)-receptor antagonist metoprolol. This was tested in conscious dogs by infusion of NaCl (20 mu mol.kg(-1).min(-1) for 180 min, NaLoad) during regular or low-sodium diet (0.03 mmol.kg(-1).min(-1) day(-1), LowNa) with and without metoprolol (2 mg/kg plus 0.9 mg.kg(-1).h(-1)). Vasopressin V-2 receptors were blocked by Otsuka compound OPC31260 to facilitate clearance measurements. Body fluid volume was maintained by servo-controlled 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 similar to 30%, ANG II by similar to 40%, and aldosterone by similar to 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 beta(1)-adrenergic control as expected; however, the acute sodium-driven decrease in PRC at constant MAP and GFR was unaffected by beta(1)-receptor blockade demonstrating that renin may be regulated without changes in MAP, GFR, or beta(1)-mediated effects of norepinephrine. Low-sodium diet augments vasopressin secretion, whereas ANP secretion is reduced.