The systemic beta-adrenergic pathway to renin secretion: relationships with the renal prostaglandin system.

Abstract

The relationship between renin release evoked by circulating beta-agonists and the renal prostaglandin (PG) system is incompletely defined. Thus, we evaluated systemic and renal hemodynamic responses to iv (0.5 micrograms/kg X min) and intrarenal arterial (0.6 micrograms/kg X min) infusions of the beta1-agonist prenalterol (PNL) in four separate groups of anesthetized dogs. Consecutive iv PNL infusions (n = 6) resulted in a reversible decrease in mean arterial pressure (130 to 117 mm Hg; P less than 0.05) and increases in cardiac output (3.93 to 4.90 liters/min; P less than 0.001), PRA (1.96 to 5.12 ng/ml X h; P less than 0.01), and 6-keto-PGF 1 alpha levels (190 to 482 pg/ml; P less than 0.01). The glomerular filtration rate and renal blood flow were modestly, but not significantly, decreased by the PNL infusions. In a second group of dogs, the infusion of the PG synthesis inhibitor indomethacin (IN; 10 mg/kg, iv; n = 7) before the second PNL infusion blunted PG increases but did not significantly modify the systemic or renal hemodynamic responses to PNL. The magnitude of the PRA and renin secretory rate (RSR) increases post-IN administration was similar to control values, but the absolute levels achieved were not as great as before IN infusion. To assess the role of the renal baroreceptor pathway to renin release after PNL, a suprarenal clamp was used to maintain a constant renal perfusion pressure during PNL infusion in a third group of dogs. In this group (n = 5), both PRA and RSR (from innervated and denervated kidneys) increased after PNL infusion, although IN again diminished the maximum PRA and RSR responses observed. Finally, the unilateral intrarenal arterial infusion of PNL in the last group of dogs did not alter PRA, RSR, or renal hemodynamics. These results demonstrate that renin release elicited by a circulating beta-agonist functions independently of PG synthesis, and that the pathway operates via an extrarenal mechanism.