Bilaterally Denervated Research Articles

Paradoxical structural effects in the unilaterally denervated spontaneously hypertensive rat kidney

To determine the effects of chronic denervation on renal vascular structure and function in young adult spontaneously hypertensive rats (SHRs). Unilateral renal denervation (SHRUDx) or sham-operation (SHRS) was performed in SHRs at 6 weeks of age. At 10 weeks, rats were allocated to one of three procedures designed to examine renal vascular structure and function. A further group underwent bilateral renal denervation. In SHRUDx or SHRS groups, either the kidneys were perfusion-fixed for stereological estimates of artery wall and lumen dimensions or for vascular casting to determine arteriole lumen diameters, or the rats were anaesthetized for estimation of glomerular capillary pressure. Chronic unilateral renal denervation had no significant effect on the development of hypertension between 6 and 10 weeks of age, as previously reported, but resulted in luminal narrowing of the interlobular artery (denervated group 52 +/- 2 mum, sham-operated group 64 +/- 1 mum; P < 0.01 for interaction between strain and treatment), without alterations in interlobular or arcuate artery wall dimensions. There were no significant effects on either afferent or efferent arteriole lumen diameters. Estimated glomerular capillary pressure was significantly lower in the denervated kidneys of SHRUDx (47 +/- 1 mmHg) compared with kidneys of the SHRS (50 +/- 1 mmHg; P < 0.04). Mean arterial pressure was approximately 12 mmHg lower in the bilaterally denervated SHRs than in the sham-operated SHRs. Although bilateral denervation attenuated the development of hypertension in SHRs, unilateral denervation did not, indicating that one neurally intact kidney was sufficient to drive the normal development of SHR hypertension, but only with apparent prohypertensive compensatory changes in the denervated kidney.

Role of atrial natriuretic factor, hemodynamic changes and renal nerves in the renal effects of intraperitoneal morphine in conscious rats.

The aim of the present study was to investigate the role of renal nerves and atrial natriuretic factor (ANF) in the mechanisms responsible for the diuresis and antinatriuresis induced by morphine in rats in a normal state of hydration. Male Wistar rats weighing 350-400 g were divided into two groups: one group was subjected to bilateral renal denervation, whereas the other consisted of sham-operated controls. The animals were placed in individual metabolic cages, and morphine (1.25, 2.5, 5.0 or 10.0 mg/kg body weight) or vehicle (0.5 ml isotonic saline) was injected intraperitoneally. Urine was collected hourly for 1 h before and 3 h after morphine injection. The lower doses of morphine (1.25 and 2.5 mg/kg body weight) induced a transient increase in urine output (from 1.17+/-0.12 to 2.49+/-0.34 and from 0.78+/-0.08 to 1.71+/-0.18 microl/min, respectively). The diuretic response to these doses was similar in bilaterally denervated rats. Higher doses (5.0 and 10.0 mg/kg body weight) induced a marked but transient reduction in the urinary flow rate during the first hour (from 0.90+/-0.11 to 0.48+/-0.05 and from 1.37+/-0.17 to 0.45+/-0.08 microl/min, respectively), followed by a delayed diuretic effect. The antidiuretic action of morphine was not observed in bilaterally denervated rats. In control rats, morphine induced a dose-dependent decrease in sodium excretion 1 h after administration, an effect that was blunted in the denervated group. The lower morphine doses (1.25 and 2.5 mg/kg body weight) elicited a transient increase in the glomerular filtration rate (GFR) in both control (from 1.23+/-0.12 to 1.67+/-0.17 and from 1.28+/-0.14 to 2.41+/-0.18 ml/min) and bilaterally denervated rats (from 1.29+/-0.14 to 1.66+/-0.17 and from 1.18+/-0.22 to 1.72+/-0.19 ml/min), whereas the higher doses (5.0 and 10.0 mg/kg body weight) produced a marked, transient GFR decrease in the controls (from 1.25+/-0.11 to 0.43+/-0.05 and from 1.13+/-0.17 to 0.47+/-0.08 ml/min) and bilaterally denervated animals (from 1.48+/-0.16 to 0.74+/-0.09 and from 1.22+/-0.15 to 0.73+/-0.06 ml/min), although the reduction was less pronounced with renal denervation. Morphine induced a transient, dose-dependent reduction in blood pressure (from 114+/-1 to 71+/-6 mm Hg at 10.0 mg/kg body weight) and a dose-dependent elevation of plasma ANF. No differences in plasma ANF were observed between control and denervated animals under basal conditions (60+/-7 vs. 42+/-6 pg/ml) or after injection of 2.5 or 5.0 mg/kg of morphine (155+/-11 vs. 167+/-9 and 360+/-9 vs. 401+/-9 pg/ml, respectively). Our data suggest that the renal responses to intraperitoneal morphine administration derive from the integration of several different actions: (1) increased ANF release; (2) decreased arterial pressure; (3) subsequent activation of renal sympathetic activity, and (4) the direct effect of morphine on tubular function.

Changes in ovine pineal gland neuron-specific enolase immunoreactivity following bilateral, but not unilateral, superior cervical ganglionectomy.

Pineal gland tissue from control and from unilaterally or bilaterally superior cervical ganglionectomized (SCGX) sheep was found to contain neuron-specific enolase immunoreactive cells and nerve fibers. Morphological characteristics of pineal cells exhibiting immunoreactivity indicated that they were predominantly pinealocytes, while other cell types were nonimmunoreactive. Whereas bilateral SCGX resulted in a reduction in the size, and possibly number, of immunoreactive cells in the pineal, unilateral denervation did not result in any significant effects when compared with control pineals. Concomitant with the reduction in immunoreactivity in bilaterally denervated pineals was a significant increase in the volume of interstitial space, but not the number of nonimmunoreactive cells. These results suggest that sympathetic nerve fibers innervating the pineal of unilaterally sympathectomized sheep exhibited a degree of neural plasticity that resulted in denervated pinealocytes being reinnervated by remaining intact nerve terminals, thus preventing the occurrence of degenerative changes normally associated with complete loss of neural input through bilateral denervation. The fact that in unilaterally denervated sheep neither left nor right SCGX produced any discernible effects in either half of the pineal indicates that nerve fibers from each of the ganglia cross over to innervate the contralateral as well as the ipsilateral pineal half. In the stalk of the pineal an extensive network of immunoreactive nerve fibers was found in both the caudal and habenular commissures, and occasionally these fibers were observed to enter the body of both intact and sympathetically denervated pineals. This latter result suggests that the sympathetic innervation enters the pineal over its surface and not via the stalk.

Role of the sympathetic innervation in the cold-induced activation of 5′-deiodinase in brown adipose tissue of the Djungarian hamster

The importance of the sympathetic innervation in the regulation of 5'-deiodinase activity in the interscapular brown adipose tissue (BAT) of the Djungarian hamster was studied. Interscapular BAT of Djungarian hamsters was either unilaterally or bilaterally denervated, and thereafter the animals were maintained at thermoneutral temperature or exposed to 0 degree C for 24 h. Denervation reduced the norepinephrine content to 2-10% of the level in the control groups. Unilateral denervation was as effective as bilateral denervation in depressing the norepinephrine content of the interscapular BAT. Cold exposure for 24 h resulted in a pronounced 5'-deiodinase activation. Denervation reduced, but did not completely prevent, the cold-induced increase in 5'-deiodinase activity. The basal level of 5'-deiodinase activity at thermoneutral temperature was not reduced by denervation. We conclude that cold-induced activation of BAT 5'-deiodinase primarily depends on the intact sympathetic innervation.

Renal nerve activity does not contribute to the development of renovascular hypertension in rats with abdominal aortic constriction

This study examines the influence of renal nerves on the development of renovascular hypertension in proximal aortic constricted rats. The rats were studied 1 week after unilateral or bilateral denervation of the renal artery. Denervation had no effect on the increase in mean arterial pressure induced by the constriction. The glomerular filtration rate and filtration fraction in control and in proximal aortic constricted rats were not influenced by the denervation. The Na excretion was increased in the denervated kidney both in control and in proximal aortic constricted rats. Plasma angiotensin II levels were not different from controls in innervated or unilaterally denervated proximal aortic constricted rats. In bilaterally denervated proximal aortic constricted rats the plasma angiotensin II levels were significantly higher. The renovascular hypertension and the alteration in renal function in proximal aortic constricted rats are not dependent on renal nerve activity.

Role of renal nerves in maintaining sodium balance in unrestrained conscious rats

This study was designed to investigate the effects of bilateral renal denervation on sodium and water balance, the renin-angiotensin system, and systemic blood pressure in unrestrained conscious rats maintained on a normal- or low-sodium diet. Renal denervation was proven by chemical and functional tests. Both bilaterally denervated rats (n = 18) and sham-denervated rats (n = 15) maintained positive sodium balance while on a normal sodium intake. Both groups were in negative sodium balance for 1 day after dietary sodium restriction was instituted but were in positive sodium balance for the following 9 days. Systolic blood pressure was higher in sham-denervated (115 +/- 3 mmHg) than in denervated rats (102 +/- 3 mmHg) while on a normal diet (P less than 0.05) and remained so during sodium restriction. Plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were significantly diminished in the denervated rats during normal sodium intake (P less than 0.05). After dietary sodium restriction, PRC increased in both groups but remained significantly lower in the denervated rats (P less than 0.05). Following dietary sodium restriction, PAC also increased significantly to levels that were similar in both groups of rats. These results demonstrate that awake unrestrained growing rats can maintain positive sodium balance on a low sodium intake even in the absence of the renal nerves. However, efferent renal nerve activity influenced plasma renin activity in these animals.

Factors causing natriuresis after hypothalamic injection of a cholinergic drug in rats.

We investigated possible mechanisms for the natriuresis seen after injection of the cholinergic drug carbamylcholine chloride (carbachol) into the lateral hypothalamus of conscious rats. In unrestrained rats injection of 1 microgram of carbachol in 1 microliter of 0.15 M NaCl solution through a permanently implanted cannula produced a significant natriuresis and kaliuresis. Injection of vehicle produced no changes. The same animals were then subjected to bilateral renal denervation (n = 13) or sham denervation (n = 13) and injected with the same solutions 1 wk later. Carbachol injection produced a natriuresis (P less than 0.0001) and a kaliuresis (P less than 0.01) in all animals studied. Both responses were of a magnitude similar to the responses seen before denervation. We studied other rats while awake but restrained, which permitted the performance of clearance studies and blood pressure measurements. Injection of carbachol produced diuresis, natriuresis, and kaliuresis in all rats, with no change in p-aminohippurate clearance and only transient change in inulin clearance. An increase in blood pressure occurred in some but not all rats. The response in rats with bilaterally denervated kidneys (n = 7) was similar to that of rats with innervated kidneys (n = 5). The natriuresis seen after cholinergic stimulation of the hypothalamus in conscious rats is not primarily mediated by inhibition of renal nerve activity and can be dissociated from changes in blood pressure, glomerular filtration rate, and renal plasma flow.

Renal excretion of sodium after bilateral renal sympathectomy in the anaesthetized and conscious rat.

1. The effect of bilateral renal denervation on sodium excretion was studied in conscious rats on normal, low and high sodium diet, and in rats recovering from anaesthesia, as well as in anaesthetized rats fed a normal sodium diet. 2. Sodium excretion of bilaterally denervated conscious rats on normal sodium intake and during either 2 weeks of sodium depletion or 6 days of sodium loading was not different from that of controls, despite changes in sodium supply of more than two orders of magnitude. Cortical noradrenaline concentration of control kidneys was 138 +/- 12 ng/g, but was only 7 +/- 3 ng/g (P less than 0 . 001) 6 weeks after denervation. 3. In rats recovering from anaesthesia urine flow, sodium excretion and glomerular filtration rate (G.F.R.) were not affected by denervation. 4. In anaesthetized non-diuretic rats on normal sodium diet chronic bilateral renal denervation increased urine flow and sodium excretion four and five times, respectively, with no changes in G.F.R. 5. Mean arterial blood pressure in bilaterally denervated anaesthetized rats and in those recovering from anaesthesia was decreased by 2 . 7 kPa, P less than 0 . 001 and 1 . 2 kPa, P less than 0 . 05, respectively. 6. The participation of renal nerves in the regulation of sodium excretion in conscious rats seems improbable. The denervation natriuresis in anaesthetized rats can be related to higher pre-denervation renal sympathetic nervous activity due to narcosis and surgical stress.