Dietary Sodium Loading Increases Arterial Pressure in Afferent Renal–Denervated Rats

Abstract

Abstract-In rats fed high sodium diet, increasing renal pelvic pressure Ն3 mm Hg activates renal mechanosensory nerves, resulting in a renorenal reflex-induced increase in urinary sodium excretion. The low activation threshold of the renal mechanosensory nerves suggests a role for natriuretic renorenal reflexes in the regulation of arterial pressure and sodium balance. If so, interruption of the afferent renal innervation by dorsal rhizotomy (DRX) at T 9 -L 1 would impair urinary sodium excretion and/or increase arterial pressure during high dietary sodium intake. DRX and sham-DRX rats were fed either a high or a normal sodium diet for 3 weeks. Mean arterial pressure measured in conscious rats was higher in DRX than in sham-DRX rats fed a high sodium diet, 130Ϯ2 vs 100Ϯ3 mm Hg (PϽ0.01). However, mean arterial pressure was similar in DRX and sham-DRX rats fed a normal sodium diet, 115Ϯ1 and 113Ϯ1 mm Hg, respectively. Steady-state urinary sodium excretion was similar in DRX and sham-DRX rats on high (17.9Ϯ2.2 and 16.4Ϯ1.8 mmol/24 h, respectively) and normal (4.8Ϯ0.3 and 5.0Ϯ0.4 mmol/24 h, respectively) sodium diets. Studies in anesthetized rats showed a lack of an increase in afferent renal nerve activity in response to increased renal pelvic pressure and impaired prostaglandin E 2 -mediated release of substance P from the renal pelvic nerves in DRX rats fed either a high or a normal sodium diet, suggesting that DRX resulted in decreased responsiveness of peripheral renal sensory nerves. In conclusion, when the afferent limb of the renorenal reflex is interrupted, a high sodium diet results in increased arterial pressure to facilitate the natriuresis and maintenance of sodium balance. Key Words: renal nerves Ⅲ hypertension, sodium dependent Ⅲ sodium, dietary Ⅲ urine Ⅲ natriuresis I n the kidney, the majority of renal sensory nerves containing substance P are located in the renal pelvic wall. 1,2 The afferent renal nerves project to the ipsilateral dorsal root ganglia at the T 6 -L 2 level, with the majority of cell bodies of the afferent renal nerves being at the T 9 -L 1 level. 3,4 The renal sensory nerves are activated by increases in renal pelvic pressure within the physiologic range. 5 The increase in afferent renal nerve activity (ARNA) produced by the increased renal pelvic pressure leads to a reflex decrease in efferent renal sympathetic nerve activity (ERSNA) and diuresis and natriuresis, ie, a renorenal reflex response. 6 Increasing renal pelvic pressure elicits a series of events eventually leading to increases in ARNA. Among the various mechanisms activated by increased renal pelvic pressure is stimulation of bradykinin-2 receptors that activate protein kinase C, which leads to activation of cyclooxygenase-2 and increased prostaglandin E 2 (PGE 2 ) synthesis. 7-9 PGE 2 activates cAMP, which leads to a calcium-dependent release of substance P from the renal sensory nerves. 10,11 Substance P increases ARNA by stimulating neurokinin-1 receptors. 12 The responsiveness of renal sensory nerves is modulated by...

A Novel Mechanism Contributing to Development of Dahl Salt–Sensitive Hypertension

“…18 -21 It is conceivable that a defect in the sensory nervous system may lead to hypertension associated with reduced sodium excretion. Indeed, sodium excretion in response to sodium loading is impaired in salt-sensitive hypertension induced by sensory nerve degeneration of neonatally capsaicin-treated rats or surgically denervated rats, 3,[22][23][24] as well as in DS rats. [25][26][27] Therefore, the susceptibility of DS rats to hypertension may be attributed, at least in part, to the lack of adequate counterregulatory action of sensory nerves, and the resistance to hypertension in DR rats may be related to an enhanced function of sensory nerves.…”

Impaired excitability of renal afferent innervation after exposure to the inflammatory chemokine CXCL1

“…In contrast, renal afferent nerves were described to act protectively against salt-sensitive hypertension and the structural renal damage of high blood pressure (24,44). A more recent study using a more selective method of renal afferent denervation suggests that this might not be the case, but it could be shown that selective renal afferent denervation was able to blunt the development of deoxycorticosterone acetate-salt hypertension (12).…”

Sensory renal innervation: a kidney-specific firing activity due to a unique expression pattern of voltage-gated sodium channels?

“…Clinical reports on patients after thermal ablation point to an independent role of afferent renal innervation on blood pressure (33). Experimental data suggest that renal afferent denervation may be protective against the development of high blood pressure (26,42) as well as the progression of renal structural damage in renal disease (6,43). Hence, nonselective thermal ablation of afferent renal nerves in resistant human hypertension may not be always beneficial since the exact pathophysiological situation is normally not well defined (27).…”