Intrarenal pelvic bradykinin-induced sympathoexcitatory reno-renal reflex is attenuated in rats exposed to chronic intermittent hypoxia.

Abstract

In this study, we hypothesized that excitatory reno-renal reflex control of sympathetic outflow is enhanced in rats exposed to chronic intermittent hypoxia (CIH) with established hypertension. Under anaesthesia, renal sensory nerve endings in the renal pelvic wall were chemically activated using bradykinin (150, 400 and 700 μmol/l) and capsaicin (1.3 μmol/l), and cardiovascular parameters and renal sympathetic nerve activity (RSNA) were measured. CIH-exposed rats were hypertensive with elevated basal heart rate and increased basal urine flow compared with sham. The intrarenal pelvic infusion of bradykinin was associated with contralateral increase in the RSNA and heart rate, without concomitant changes in blood pressure. This was associated with a drop in the glomerular filtration rate, which was significant during a 5 min period after termination of the infusion but without significant changes in urine flow and absolute sodium excretion. In response to intrarenal pelvic infusion of 700 μmol/l bradykinin, the increases in RSNA and heart rate were blunted in CIH-exposed rats compared with sham rats. Conversely, the intrarenal pelvic infusion of capsaicin evoked an equivalent sympathoexcitatory effect in CIH-exposed and sham rats. The blockade of bradykinin type 1 receptors (BK1R) suppressed the bradykinin-induced increase in RSNA by ∼33%, with a greater suppression obtained when bradykinin type 2 receptors (BK2R) and BK1R were contemporaneously blocked (∼66%). Our findings reveal that the bradykinin-dependent excitatory reno-renal reflex does not contribute to CIH-induced sympathetic hyperactivity and hypertension. Rather, there is evidence that the excitatory reno-renal reflex is suppressed in CIH-exposed rats, which might relate to a downregulation of BK2R.