Renal afferents signaling diuretic activity in the cat.

Abstract

Mechanoreceptors and chemoreceptors have been identified inside the kidney, but their functional role is still largely unclear. The aim of this study was to investigate whether changes in urine output could modify the discharge rate of renal afferent fibers. Experiments were performed in anesthetized cats in which afferent renal nerve activity (ARNA) was recorded by standard electrophysiological techniques from a centrally cut renal nerve. Arterial pressure, renal blood flow velocity, urine flow rate, and renal pelvic pressure were also measured. Three diuretic maneuvers were tested in the same cat: intravenous administration of physiological saline (8 to 13 mL/min for 2 minutes), furosemide (1 mg/kg), and atrial natriuretic peptide (ANP, 1 microgram/kg). The three maneuvers increased urine flow rate and pelvic pressure, respectively, 137.0 +/- 20.6% and 136.8 +/- 21.1% (saline), 148.6 +/- 31.7% and 139.6 +/- 43.5% (furosemide), and 75.9 +/- 7.9% and 62.1 +/- 21.2% (ANP) at the time of the maximum response. Arterial pressure slightly increased after saline, did not change after furosemide, and slightly decreased after ANP. Renal blood flow increased after saline and did not change after furosemide and ANP. The three maneuvers increased ARNA by 98.4 +/- 15.2% (saline), 270.7 +/- 100.8% (furosemide), and 59.6 +/- 23.4% (ANP). Changes in ARNA significantly correlate with changes in both pelvic pressure and urine flow rate. Our data demonstrate that increments in urine flow rate increase the firing rate of renal afferent fibers and suggest that (1) pelvic pressure is the major determinant of the neural response, and (2) this increased afferent discharge is due to activation of renal mechanoreceptors.

Renal Afferents Responsive to Chemical and Mechanical Pelvic Stimuli in the Rabbit

“…As the increased afferent renal nerve activity was associated with contralateral diuresis and natriuresis, a role of renal mechanoreceptors in the control of body water and sodium balance has been suggested [4, 14, 151. In previous experiments, performed in anaesthetised cats [16], we have demonstrated that diuretic manoeuvres activate renal mechanosensitive fibres by increasing pelvic pressure, thus suggesting a role of renal mechanoreceptors in monitoring urine volume in the cat [16].…”

Everything we always wanted to know about furosemide but were afraid to ask

“…Several studies have demonstrated that furosemide can directly activate the renal sympathetic nervous system (124), independent from the RAS (123). This could well be elicited by a change in the local micro-environment of the afferent nerve ending in the renal interstitium (52). Nevertheless, renal denervation did not affect the natriuresis evoked by furosemide acutely (146) in lambs or chronically (122) in rats under physiological conditions.…”

Interactions Between Furosemide and the Renal Sympathetic Nerves

“…Since the reflex pressor response and reflex increase in sympathetic nerve activity in response to stimulation of ARNA is severely blunted during anesthesia (Smits & Brody 1984;Faber & Gettes 1987;Janssen et a/. 1989b), the lack of correlation between increased ARNA and increased arterial pressure during furosemide diuresis in the study by Genovesi et a/. (1993) could be related to the use of anesthesia.…”

“…In this study, furosemide stimulated prostacyclin release and increased cyclic GMP formation and since both actions were inhibited by a bradykinin type-2 receptor antagonist, the authors concluded that furosemide stimulates endothelial synthesis and release of kinins which in turn stimulates prostacyclin formation. Whereas this mechanism may be important for stimulation of sensory neurons (IX; Nerdrum et al 1986;Uchida & Murao 1974;Ohno et al 1984;Kopp & Smith 1993;Genovesi et al 1993), the direct vasorelaxant effect of furosemide on isolated arteries being endotheliumindependent suggests that endothelial kinin release is functionally of minor significance for direct arteriolar effects of furosemide. Whether furosemide stimulates kinin release in endothelium from venous vessels is unknown.…”