Kinin B2 receptors mediate blockade of atrial natriuretic peptide natriuresis induced by glucose or feeding in fasted rats

We have shown previously that the kininogen-derived peptides bradykinin, pr okinins, and PU-D1, given intravenously or into the duodenal lumen, block t he atrial natriuretic peptide (ANP)-induced diuretic-natriuretic effect in fasting, anesthetized rats infused with isotonic glucose. HOE-140, an inhib itor of bradykinin B2 receptors, completely suppresses this ANP blockade. W hen intravenous glucose infusion is omitted, the above-described inhibition of ANP does not take place. Therefore, to clarify the role of glucose and/ or feeding in this; phenomenon, we used fasted, anesthetized rats to test h ow the ANP excretory response was affected by (1) short-ter lm feeding befo re anesthesia, (2) 1 mL of isotonic glucose introduced into the stomach, an d (3) the interaction of HOE-140 with these treatments. In addition, we tes ted the effects of 1 mt of intragastric glucose administration and HOE-140 on urinary excretion in awake rats. In anesthetized rats, both glucose admi nistration and feeding significantly inhibited the diuretic-natriuretic eff ect of ANP for up to 90 minutes. Similarly, intragastric glucose delayed sp ontaneous sodium and water excretion for 90 minutes in awake rats. In all 3 cases, pretreatment with HOE-140 (2.5 mu g IV) fully prevented the inhibit ion of ANP excretory action, ruling out osmotic effects as the cause of red uced diuresis. These results indicate that the presence of glucose in the d igestive tract triggers an inhibitory effect on ANP renal actions that requ ites activation of kinin B2 receptors, providing strong support to our hypo thesis that during the early prandial period, gastrointestinal signals elic it a transient blockade of renal excretion with a mechanism involving the k allikrein-kinin system.