Absence Of Renal Nerves Research Articles

The denervation or activation of renal sympathetic nerve and renal blood flow.

The denervation or activation of the sympathetic nerve in the kidney can affect renal hemodynamics. The sympathetic nervous system regulates the physiological functions of the kidneys. Stimulation of sympathetic efferent nerves affects various parameters related to renal hemodynamics, including sodium excretion, renin secretion, and renal blood flow (RBF). Hence, renal sympathetic fibers may also play an essential role in regulating systemic vascular resistance and controlling blood pressure. In the absence of renal nerves, the hemodynamics response to stimuli is negligible or absent. The effect of renal sympathetic denervation on RBF is dependent on several factors such as interspecies differences, the basic level of nerve activity in the vessels or local density of adrenergic receptor in the vascular bed. The role of renal denervation has been investigated therapeutically in hypertension and related disorders. Hence, the dynamic impact of renal nerves on RBF enables using RBF dynamic criteria as a marker for renal denervation therapy.

Atrial natriuretic peptide has no potential to protect against endotoxin-induced acute renal failure in the absence of renal nerves.

Atrial natriuretic peptide (ANP) has been shown to have the potential to restore renal function after ischemic injury, an underlying component of endotoxin (Et)-induced acute renal failure, and is known to counteract renal sympathetic nerve activity in renal function. We have recently found that renal denervation restores the Et-induced renal dysfunction. The purpose of this study was to examine effects of ANP infusion on the Et-induced acute renal failure in the absence of renal nerves. Ten to 14 days after bilateral renal denervation (DNX), Wistar rats (250 to 300 g body wt) were used in the acute experiment. Rats with intact renal nerves (INN) served as controls. Following control clearance measurements, rats were intravenously injected with 4 mg/kg Et (Escherichia coli, 055: B5). During endotoxemia, rats were infused with 10 microg/kg/h ANP or saline vehicle. Et injection reduced the glomerular filtration rate (GFR) significantly in saline-infused INN and DNX rats. ANP infusion restored the greatly reduced GFR to the pre-endotoxemia level in DNX rats but not in INN rats. There was significant difference between the ANP- and saline-infused DNX rats in the percentage change relative to the basal GFR value during the ANP infusion period. ANP infusion did not improve the hyponatriuresis and oliguria after Et administration, which is independent of renal nerves. In conclusion, ANP infusion has a minor reno-protective effect in rats with Et-induced acute renal failure in the absence of the renal nerves.

Effects of renal denervation on cardiovascular and renal responses to ACE inhibition in conscious lambs.

Effects of renal denervation on cardiovascular and renal responses to ACE inhibition in conscious lambs. J. Appl. Physiol. 83(2): 414-419, 1997.-Cardiovascular and renal effects of either the angiotensin-converting enzyme inhibitor captopril or vehicle were measured in chronically instrumented lambs in the presence (intact; n = 6) and absence of renal sympathetic nerves (denervated; n = 5) to determine whether there was an interaction between the renin-angiotensin system and renal sympathetic nerves early in life. Captopril caused a similar decrease in mean arterial pressure (P < 0. 001) in intact and denervated lambs, predominantly through a decrease in diastolic pressure. Heart rate was increased from 177 +/- 34 to 213 +/- 22 (SD) beats/min during captopril compared with vehicle infusion in intact lambs. In denervated lambs, basal heart rates were elevated to 218 +/- 33 beats/min; there was no further increase in heart rate during captopril compared with vehicle infusion. Captopril infusion caused a decrease in renal vascular resistance but only in the absence of renal nerves. These findings provide evidence to suggest that early in life there is an interaction between renal sympathetic nerves and the renin-angiotensin system in regulating renal hemodynamics and the baroreflex control of the heart.

Renal Responses to Acute Volume Expansion in Young Spontaneously Hypertensive Rats

The renal responses to acute volume expansion (VE) were measured from intact and denervated kidneys in 5 week old spontaneously hypertensive rats (SHR). Urine flow and sodium excretion were measured before, during and after VE from innervated and denervated kidneys in anesthetized (Inactin--0.1 g/kg, ip) age and sex matched SHR and normotensive Wistar Kyoto (WKY) rats. Mean arterial pressure was 23 mm Hg higher in SHR than in WKY. During VE the increment in urinary flow rate and sodium excretion from both innervated and denervated kidneys were greater in SHR than WKY. In another group of SHR, renal perfusion pressure was maintained at a level similar to the arterial pressure in the WKY group (84 mm Hg). When renal perfusion pressure was controlled at the lower level in the SHR there was no longer the increase in diuresis and natriuresis in response to acute VE. Examining differences within a strain, the SHR demonstrate a greater increase in diuresis and natriuresis in response to VE in the absence of renal nerves, unlike the WKY. In conclusion, these results suggest that there is a greater diuresis and natriuresis in the young SHR due to increased renal perfusion pressure and the renal nerves produce a greater retention of water and sodium in SHR compared to WKY.

Diuretic and natriuretic responses to ANF in the presence and absence of renal nerves in DOCA-salt hypertensive rats.

To determine if renal nerves contributes in the renal response to atrial natriuretic factor (ANF) in DOCA-salt hypertensive rats, diuretic and natriuretic responses to ANF were measured in Inactin (0.1 g/kg, i.p) anesthetized rats with unilateral renal denervation. Rats were assigned to either a control group (108 +/- 6 mmHg), or one of two DOCA-salt groups (injected with deoxycorticosterone acetate, DOCA, 25 mg/week, and given 0.9% saline to drink for 4 weeks); a) DOCA-salt group (137 +/- 6 mmHg) and b) DOCA-salt-BPC group (with blood pressure controlled at the level of the femoral artery (102 +/- 3 mmHg) by an occluder on the abdominal aorta proximal to the right renal artery). Urine flow and sodium excretion in response to ANF infusion (0.3 micrograms/min/kg) were measured from intact and denervated kidneys of control and DOCA-salt treated rats. ANF infusion produced a significant increase in diuresis and natriuresis in all three groups of rats. Urine flow and sodium excretion in response to ANF were significantly less in the intact kidney but not the denervated kidneys of the DOCA-salt rats compared to control rats. These results indicate that renal nerves contribute to the blunted renal responses to ANF in DOCA-salt rats. Renal responses also were significantly smaller in both intact and denervated kidneys of DOCA-salt-BPC rats (in which arterial pressure was reduced) compared to DOCA-salt rats. Overall, these results indicate that both renal nerves and arterial pressure determine the natriuretic and diuretic actions of ANF in DOCA-salt hypertensive rats.

Role of renal sympathetic nerves in lambs during the transition from fetal to newborn life.

To determine the role of renal sympathetic nerves in influencing renal function during the transition from fetal to newborn life, studies were carried out in conscious, chronically instrumented fetal sheep with either bilateral renal denervation (n = 11) or intact renal nerves (n = 12), 3-6 d after surgery. Endocrine, renal, and cardiovascular parameters were measured before and after delivery of lambs by cesarean section. Blood pressure and heart rate were similar in intact and denervated fetuses, and increased after delivery in both groups. There was also a transient diuresis and natriuresis, in the immediate postnatal period, the response being significantly greater in denervated than intact lambs (P less than 0.05). By 24 h postnatally, fluid and electrolyte excretions were similar in both groups, and significantly less than fetal levels. In the absence of renal nerves, the normal rise in plasma renin activity at birth was attenuated. These data provide evidence that renal sympathetic nerves play an important role during the transition from fetal to newborn life, and support the premise that birth is associated with sympathetic activation.

Role of Renal Nerves and Vasopressin in Renal Responses to Acute Volume Expansion in Rats

This study was to determine whether the presence or absence of renal nerves and vasopressin altered the diuretic and natriuretic responses to acute volume expansion. Two forms of volume expansion were used: (i) inflation of a small balloon in the veno-atrial junction and (ii) an infusion of isotonic saline at a rate of 1 ml/min for a period of 15 min, approximately 7% of body weight. Balloon inflation produced a significant diuresis from both the intact and denervated kidneys but only produced a significant natriuresis from the intact kidney. Volume expansion (infusion of saline) produced a significant diuresis and natriuresis from both intact and denervated kidneys. Blocking the V2 receptor for vasopressin with a V2-specific receptor blocker d(CH2)5[D-Ile2,Val4]AVP (40 micrograms/kg bolus dose followed by infusion of 4 micrograms/kg/min) did not alter the diuretic and natriuretic responses to volume expansion. However, the absence of renal nerves or the absence of actions of vasopressin produced a significant reduction in the capacity of the kidneys to increase the relative amount of diuresis or natriuresis, thus losing the control over output; i.e., absence of renal nerves only allowed 12-fold increase in diuresis to volume expansion compared with 25-fold in the intact state and absence of vasopressin only allowed 4.6-fold increase in diuresis to volume expansion compared with 25-fold in the intact state. Examining the "volume reflex" in terms of a control system trying to regulate fluid balance, the presence of either renal nerves or actions of vasopressin allows the volume regulating system a greater range in which to control the diuresis and natriuresis (making it possible to fine tune the output to much greater extent).

Mechanism of the antidiuretic effect associated with interruption of parasympathetic pathways.

The present experiments were undertaken to investigate the mechanism whereby the parasympathetic nervous system may be involved in the renal regulation of solute-free water excretion. The effects of interruption of parasympathetic pathways by bilateral cervical vagotomy were examined in eight normal and seven hypophysectomized anesthetized dogs undergoing a water diuresis. In the normal animals cervical vagotomy decreased free-water clearance (C(H2O)) from 2.59+/-0.4 se to -0.26+/-0.1 ml/min (P < 0.001), and urinary osmolality (U(osm)) increased from 86+/-7 to 396+/-60 mOsm/kg (P < 0.001). This antidiuretic effect was not associated with changes in cardiac output, renal perfusion pressure, glomerular filtration rate, renal vascular resistance, or filtration fraction and was not affected by renal denervation. A small but significant increase in urinary sodium and potassium excretion was observed after vagotomy in these normal animals. Pharmacological blockade of parasympathetic efferent pathways with atropine, curare, or both was not associated with an alteration in either renal hemodynamics or renal diluting capacity. In contrast to the results in normal animals, cervical vagotomy was not associated with an antidiuretic effect in hypophysectomized animals. C(H2O) was 2.29+/-0.26 ml/min before and 2.41+/-0.3 ml/min after vagotomy, and U(osm) was 88+/-9.5 mOsm/kg before vagotomy and 78+/-8.6 mOsm/kg after vagotomy in the hypophysectomized animals. Changes in systemic or renal hemodynamics or electrolyte excretion were also not observed after vagotomy in these hypophysectomized animals. On the basis of these results, we conclude that the antidiuretic effect associated with cervical vagotomy is initiated by interruption of parasympathetic afferent pathways and is mediated by increased endogenous release of vasopressin. This antidiuresis was also demonstrated to occur in the absence of renal nerves and alterations in systemic and renal hemodynamics.