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 (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 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/min for 180 min, NaLoad) during regular or low-sodium diet (0.03 mmol/kg/d, LowNa) with and without metoprolol (2 mg/kg plus 0.9 mg/kg/h). Vasopressin V2 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 AngII by 30-40%, increased plasma ANP and tripled potassium excretion. LowNa per se increased PRC (+53%), AngII (+93%), and aldosterone (+660%), and shifted the vasopressin function curve to the left. NaLoad elevated plasma [Na(+)] by 4.5% and vasopressin by 3-fold, but MAP and plasma ANP remained unchanged. NaLoad decreased PRC by ~30%, AngII by ~40%, and aldosterone by ~60% irrespective of diet and metoprolol. The natriuretic response to NaLoad was augmented during metoprolol irrespective 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 while ANP secretion is reduced. Key words: blood pressure,, angiotensin, aldosterone, natriuresis.