Endogenous Angiotensin II Modulates the Responsiveness of Renal Pelvic Mechanosensitive Neurons.

Abstract

15 Increased (↑) renal pelvic pressure by increased urine flow rate or acute ureteral obstruction activates mechanosensitive neurons in the renal pelvic wall. Activation of these neurons increases ipsilateral afferent renal nerve activity (ARNA) and contralateral urinary sodium excretion (UNaV), i.e. a renorenal reflex. Activation of cyclooxygenase 2 (COX-2) contributes to the ARNA response to ↑ renal pelvic pressure. Since renal medullary COX-2 is upregulated by high Na+ diet, we studied if the responsiveness of renal mechanosensitive neurons is altered by changes in dietary Na+. High Na+ rats were placed on normal Na+ diet and 0.9% NaCl to drink and low Na+ rats on Na+ deficient diet and tap water. ↑ renal pelvic pressure 2.5, 7.5 and 15 mmHg for 3 min increased ipsi ARNA 10±1%†, 21±2%† and 37±5%† in 6 high Na+ rats and 1±0%, 10±0%† and 19±3%† in 5 low Na+ diet rats (†p<0.05). The contra UNaV responses paralleled the ARNA responses, being 0.4±0.1, 1.1±0.3 and 1.4±0.5 μE/min/g in high Na+ rats and 0±0, 0.1±0.1 and 0.2±0.1 μE/min/g in low Na+ rats. Thus, the renorenal reflexes are suppressed by low Na+ diet. Angiotensin (ANG) is increased by low Na+ diet to facilitate Na+ retention. Thus, we speculated that ANG would suppress the activation of the natriuretic renorenal reflexes in low Na+ diet rats. Renal pelvic pressure was increased before and during renal pelvic perfusion with the AT1 receptor antagonist losartan, 200 μg/ml, in low Na+ rats and before and during pelvic perfusion with ANGII, 15 nM, in high Na+ rats. In 8 low Na+ rats, losartan enhanced the ARNA responses to ↑ renal pelvic pressure 2.5 and 7.5 mmHg, ARNA responses being 2±1% and 14±1%‡ before and 13±2%‡ and 22±3%‡ during losartan. Conversely in 8 high Na+ rats, ANGII suppressed the ARNA responses to ↑ renal pelvic pressure, ARNA responses being 10±1%‡ and 23±3%‡ before and 1±1% and 11±2%‡ during ANGII (‡p<0.01). Conclusion: Changes in dietary Na+ modulate the responsiveness of the afferent renal nerves via the renin angiotensin system. Activation of the renorenal reflexes may contribute to increased UNaV during excess Na+ intake. Of note, renorenal reflexes are impaired in SHR which are characterized by Na+ retention.