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Regeneration of the hepatic nerves following surgical denervation of the liver in dogs.

This study was conducted to examine the regeneration process of hepatic nerves following surgical hepatic denervation in dogs. A denervation model was surgically created by removing all visible nerves around the hepatoduodenal ligament along with the peri-hepatic tissues. The hepatic nerves were examined on the hepatic specimens taken at 1 week, 1 month and 3 months post-denervation by means of immunohistochemical staining, and also electron microscopy. At 1 week post-denervation, the extrinsic hepatic nerves were observed not to have regenerated. However, at 1 month post-denervation, GAP-43-positive nerves were identified and regenerating axons were shown to be present on electron microscopic observation. The immunoreactivity for anti-GAP-43 antibody was not shown any longer at 3 months post-denervation, and the regenerated nerve axons were shown to be similar to those at pre-denervation on ultrastructural study. Results of the present study suggested that regeneration of the extrinsic hepatic nerves began to appear about 1 month after the hepatic denervation, and was completed by 3 months post-denervation.

Animals↗

Length-tension relations of smooth muscle from normal and denervated rat urinary bladders.

Urinary bladders of rats were denervated by bilateral excision of the pelvic ganglion and removed 10 days after the operation. They were filled with 0.75 ml saline and a longitudinal muscle strip was marked out, measured and dissected out. Strips from normal bladders filled with the same volume were used as controls. Denervated bladders were 4-5 times heavier than control bladders. Muscle strips from denervated bladders showed, in contrast to controls, marked phasic spontaneous contractions which were unaffected by tetrodotoxin, indicating a myogenic origin. Active tension in response to AC stimulation was measured at different lengths. In relation to the in situ length (Lin situ) at 0.75 ml the denervated strips had to be stretched to much greater extent than controls in order to reach optimum length (L0) for force development. Furthermore, the denervated strips shortened less in relation to Lin situ than the controls. If active length-tension relations were expressed in relation to L0, the difference between denervated and control strips was abolished. Maximal active force was the same for denervated and control strips. Water content increased significantly in denervated bladders. The results suggest a remodelling of the smooth muscle structure in denervated bladders; the characteristics of the contractile machinery seem, however, to be unaltered.

Animals↗

Secretory and structural changes in the parotid salivary gland of sheep and lambs after parasympathetic denervation.

The effect of the parasympathetic nerve supply on the development of the parotid gland in the immature lamb and its maintenance in the adult sheep has been investigated by unilateral postganglionic denervation. Seventy-seven to ninety-three days after denervation secretory activity of the gland was examined and material taken for histological examination. The adult denervated glands secreted at lower rates than the innervated and their atropine-resistant secretory flow was reduced to as low as one fifth of that of the innervated glands. In two lambs an atropine-resistant flow did not develop in the denervated glands: in another two, flows of saliva from the denervated glands were present but were much less than in the contralateral innervated glands. After denervation glands were, with one exception, smaller than the contralateral innervated glands. The acinar cells of the denervated adult and lamb glands were smaller than the cells of the innervated glands but similar in size to those of 7-14 day old unoperated control lambs. Acinar cells in denervated glands had periodic acid Schiff staining material but the staining reaction to pyronin-methyl green was similar in the innervated and denervated. The results indicate that the integrity of the parasympathetic innervation is essential for the development of the parotid gland of the sheep and for its maintenance in the adult animal.

Age Factors↗

Capillary supply and gene expression of angiogenesis-related factors in murine skeletal muscle following denervation.

Capillary supply of skeletal muscle decreases during denervation. To gain insight into the regulation of this process, we investigated capillary supply and gene expression of angiogenesis-related factors in mouse gastrocnemius muscle following denervation for 4 months. Frozen transverse sections were stained for alkaline phosphatase to detect endogenous enzyme in the capillary endothelium. The mRNA for angiogenesis-related factors, including hypoxia inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), kinase insert domain-containing receptor/fetal liver kinase-1 (KDR/Flk-1), fms-like tyrosine kinase (Flt-1), angiopoietin-1 and tyrosine kinase with Ig and epidermal growth factor(EGF) homology domain 2 (Tie-2), was analysed using a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The fibre cross-sectional area after denervation was about 20% of the control value, and the capillary to fibre ratio was significantly lower in denervated than in control muscles. The number of capillaries around each fibre also decreased to about 40% of the control value. These observations suggest that muscle capillarity decreases in response to chronic denervation. RT-PCR analysis showed that the expression of VEGF mRNA was lower in denervated than in control muscles, while the expression of HIF-1alpha mRNA remained unchanged. The expression levels of the KDR/Flk-1 and Flt-1 genes were decreased in the denervated muscle. The expression levels of angiopoietin-1 but not Tie-2 genes were decreased in the denervated muscle. These findings indicate that reduction in the expression of mRNAs in the VEGF/KDR/Flk-1 and Flt-1 as well as angiopoietin-1/Tie-2 signal pathways might be one of the reasons for the capillary regression during chronic denervation.

Angiogenic Proteins↗

The membrane potential of rat diaphragm muscle fibres and the effect of denervation.

1. Resting membrane potentials of rat diaphragm muscles were measured in vitro after previous denervation for 0-10 days. In some experiments denervated muscles were incubated in vitro for 3 hr while in others they were cultured for 15-24 hr to allow adequate exposure to drugs before recording. 2. It was found that resting membrane potentials, within 2-5 mm of the site of nerve section were significantly lower, within 3 hr, than resting membrane potentials measured more than 9 mm away from site of nerve section. This difference could be reduced or abolished by bathing preparations in solutions containing adrenaline (10 muM), noradrenaline (10 muM) or isoprenaline (10 muM) or dibutyryl cyclic AMP (10 muM-0-25 mM in the presence of 2 mM theophylline). Cyclic AMP (0-5 mM) was ineffective. 3. Application of solutions containing dibutyryl cyclic AMP for 3 hr also raised the resting membrane potential of muscles denervated 4-5 days previously. Culture studies showed that this effect was sustained when the time of incubation was 24 hr. 4. Incubating freshly denervated preparations with cycloheximide (22 mug/ml.) or actinomycin D (1 mug/ml.) did not prevent the development of the early (3 hr) fall in resting membrane potential despite a concomitant inhibition of RNA or protein synthesis. Culturing freshly denervated muscles in solutions containing cycloheximide (10 or 25 mug/ml.) which blocked 93% of protein synthesis, did not prevent the expected drop in resting membrane potential after 15 or 24 hr. 5. It was found that exposure to ouabain (1 or 5 mM) produced a rapid (15 min) fall in resting membrane potential in innervated and denervated preparations treated with dibutyryl cyclic AMP but not denervated preparations. After 5 days denervation cyclic AMP levels in muscle were increased by about 40%. 6. It is suggested that upon denervation an electrogenic action of a NA+-pump is blocked and that dibutyryl cyclic AMP and catecholamines are capable of stimulating this pump.

Animals↗

Calcium current inactivation in denervated rat skeletal muscle fibres.

1. The inactivation of the calcium current (ICa) was studied in single extensor digitorum longus muscle fibres of the rat. Denervation was performed by surgically removing 6-8 mm of the sciatic nerve at the sciatic notch. Electrical recordings were carried out using the double Vaseline-gap technique. Normal fibres were used as controls. 2. The time course of the onset of ICa inactivation was studied with double pulse experiments. Denervation after 14 days slowed down the onset of the inactivation process. Two depolarizing pulses with variable interpulse potential were applied. The rate of recovery from ICa inactivation was analysed with long interpulse intervals (9 to 1 s). The time constants for ICa inactivation (tau i) at -90 mV potential were 4.3 and 2.2 in normal and 14 day-denervated fibres respectively. 3. The onset of ICa inactivation was studied with a double pulse protocol with variable duration of the first pulse with constant interval (120 ms) to the second pulse (300 ms). The plot of [ICa (pulse 2)/ICa(pulse 1)]--first pulse duration relationship was fitted with a single exponential equation. The inactivation time constant (tau h) values for normal and denervated fibres were 428 and 619 ms, respectively. 4. The h infinity-Vm relationship for denervated fibres was shifted toward more negative potentials and ICa did not fully inactivate with large prepulses. The h infinity-Vm relationship was fitted with a Boltzmann equation I/Imax = 1 - (A/[1 + (exp ((Vm1/2 - Vm)/kh))]) where Vm is the potential during the conditioning pulse and A is an amplitude factor. In normal fibres, Vm1/2 (mid-point) and kh (slope) values were -28.7 mV and 7.6 mV, respectively. In 14-day-denervated fibres they were -42.2 and 8.6 mV, respectively. 5. A temperature rise from 17 to 27 degrees C greatly increased the inactivation rate of ICa. This effect was similar in control and denervated fibres. The temperature coefficient quotient (Q10) values for ICa amplitude in normal and denervated fibres were 2.4 (n = 8) and 2.3 (n = 8), respectively. The Q10 values for the inactivation time constant (tau h) were 5.14 and 5.25, respectively. ICa decay during 1 s pulses was fitted to a single exponential function in normal fibres at 17 and 27 degrees C; the time constant values were tau h = 460 +/- 53 ms and tau h = 92 +/- 17 ms, respectively. The time constants of denervated fibres at both temperatures were tau h = 644 +/- 102 ms and 146 +/- 17 ms, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Effect of renal denervation on arterial pressure and renal norepinephrine concentration in Wistar-Kyoto and spontaneously hypertensive rats.

Renal norepinephrine (NE) concentration was measured at 2-week intervals after bilateral denervation of the kidneys in 5-week-old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Sham-operated rats of both strains served as controls. Renal denervation significantly delayed but did not prevent the development of hypertension in SHR. Kidney NE concentration in renal-denervated SHR was 13, 25, 33, and 35% of that found in sham-operated SHR at 2, 4, 6, and 8 weeks, respectively, after denervation. Similarly, kidney NE concentration in renal-denervated WKY rats was 11, 24, 32, and 34% of controls but arterial pressure was not significantly altered. Renal-denervated SHR subjected to a second denervation operation 3 weeks after the initial operation continued to develop hypertension similar to those having only one operation. The results of this study support the hypothesis that renal nerves are involved in the hypertensive process in SHR during the early stages and suggest that renal reinnervation may occur within several weeks after denervation; however, the delayed rise in arterial pressure in renal-denervated SHR is not due to renal reinnervation.

Animals↗

Reversal of denervation-induced insulin resistance by SHIP2 protein synthesis blockade.

Short-term muscle denervation is a reproducible model of tissue-specific insulin resistance. To investigate the molecular basis of insulin resistance in denervated muscle, the downstream signaling molecules of the insulin-signaling pathway were examined in intact and denervated soleus muscle of rats. Short-term denervation induced a significant fall in glucose clearance rates (62% of control, P < 0.05) as detected by euglycemic hyperinsulinemic clamp and was associated with a significant decrease in insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR; 73% of control, P < 0.05), IR substrate 1 (IRS1; 69% of control, P < 0.05), and IRS2 (82% of control, P < 0.05) and serine phosphorylation of Akt (39% of control, P < 0.05). Moreover, denervation reduced insulin-induced association between IRS1/IRS2 and p85/phosphatidylinositol (PI) 3-kinase. Nevertheless, denervation caused an increase in PI 3-kinase activity associated with IRS1 (275%, P < 0.05) and IRS2 (180%, P < 0.05), but the contents of phosphorylated PI detected by HPLC were significantly reduced in lipid fractions. In the face of the apparent discrepancy, we evaluated the expression and activity of the 5-inositol, lipid phosphatase SH2 domain-containing inositol phosphatase (SHIP2), and the serine phosphorylation of p85/PI 3-kinase. No major differences in SHIP2 expression were detected between intact and denervated muscle. However, serine phosphorylation of p85/PI 3-kinase was reduced in denervated muscle, whereas the blockade of SHIP2 expression by antisense oligonucleotide treatment led to partial restoration of phosphorylated PI contents and to improved glucose uptake. Thus modulation of the functional status of SHIP2 may be a major mechanism of insulin resistance induced by denervation.

Animals↗

Sympathetic but not sensory denervation stimulates white adipocyte proliferation.

White adipocyte proliferation is a hallmark of obesity, but it largely remains a mechanistic mystery. We and others previously demonstrated that surgical denervation of white adipose tissue (WAT) triggers increases in fat cell number, but it is unknown whether this was due to preadipocyte proliferation or maturation of existing preadipocytes that allowed them to be counted. In addition, surgical denervation severs not only sympathetic but also sensory innervation of WAT. Therefore, we tested whether sympathetic WAT denervation triggers adipocyte proliferation using 5-bromo-2'-deoxyuridine (BrdU) as a marker of proliferation and quantified BrdU-immunoreactive (ir) cells that were co-labeled with AD-3-ir, an adipocyte-specific membrane protein marker. The unilateral denervation model was used for all experiments where Siberian hamster inguinal WAT (IWAT) was unilaterally denervated, the contralateral pad was sham denervated serving as a within-animal control, and then BrdU was injected systemically for 6 days. When IWAT was surgically denervated, severing both sympathetic and sensory nerves, tyrosine hydroxylase (TH)-ir, a sympathetic nerve marker, and calcitonin gene-related peptide (CGRP)-ir, a sensory nerve marker, were significantly decreased, and BrdU+AD-3-ir adipocytes were increased approximately 300%. When IWAT was selectively sensory denervated via local microinjections of capsaicin, a sensory nerve-specific toxin, CGRP-ir, but not TH-ir, was decreased, and BrdU+AD-3-ir adipocytes were unchanged. When IWAT was selectively sympathetically denervated via local microinjections of 6-hydroxy-dopamine, a catecholaminergic-specific toxin, TH-ir, but not CGRP-ir, was significantly decreased, and BrdU+AD-3-ir adipocytes were increased approximately 400%. Collectively, these data provide the first direct evidence that sympathetic nerves inhibit white adipocyte proliferation in vivo.

Adaptation, Physiological↗

Functional reinnervation and development of supersensitivity to NE after renal denervation in rats.

The time course for functional reinnervation and development of supersensitivity to norepinephrine (NE) in the denervated rat kidney was studied using an in situ kidney preparation perfused at constant flow. Changes in perfusion pressure were measured during renal nerve stimulation (RNS, 1-10 Hz) and after administration of NE (1-50 ng, ia) up to 8 wk after unilateral renal denervation or a sham operation. During the first 2 wk after denervation, supersensitivity to NE was present, but there was no response to RNS. Between 24 and 32 days after denervation, RNS produced responses averaging 40% of control in denervated kidneys and supersensitivity to NE was still present. A fluorescence assay was used to determine that the NE concentration in kidneys 24-32 days after denervation was less than 30% of that found in control kidneys. At 8 wk, average responses to RNS in denervated kidneys were not significantly different from innervated kidneys, while supersensitivity to NE was still present. These results indicate that functional reinnervation of the renal vasculature begins to occur between 14 and 24 days after denervation, and that complete return of function may occur by 8 wk. The response to RNS during reinnervation appears to be due to a combination of regeneration of nerve fibers and denervation supersensitivity to NE.

Animals↗

Lysosomal proteolysis in distally or proximally denervated rat soleus muscle.

We examined the mechanism of accelerated proteolysis in denervated rat soleus muscles. The soleus was denervated by severing either the tibial nerve (proximal, short stump) or sciatic nerve (distal, long stump) at 24, 48, 72, or 96 h before excision. Twenty-four hours after denervation, the extent of atrophy was similar for proximal and distal denervation, although lysosomal latency declined in both groups. After 48 and 72 h, denervation resulted in a decline in protein content, an increase in in vitro protein degradation, and a decline in lysosomal latency, all of which were greater in proximally denervated than in contralateral distally denervated muscles. These differences between acute responses of proximally and distally denervated muscles suggest the retention of some factor in the longer nerve stump that attenuates atrophy. After 96 h, total protein loss, protein degradation, and lysosomal latency were similar for proximal and distal denervation, suggesting the loss of axoplasmic flow from the long nerve stump.

Animals↗

Renal denervation supersensitivity revisited.

To determine whether the chronically denervated kidney is supersensitive to either physiological or pathophysiological plasma levels of norepinephrine (NE), studies were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated and innervated kidneys. Plasma NE concentration was increased by chronic infusion of NE (4-5 days) at rates of 25, 100, and 200 ng . kg-1 . min-1. Twenty-four-hour control values for mean arterial pressure (MAP), plasma NE concentration, and ratios for urinary sodium and potassium excretion from denervated and innervated kidneys (Den/Inn) were 94 +/- 4 mmHg, 145 +/- 24 pg/ml, 1.05 +/- 0.05, and 0.97 +/- 0.07, respectively. With infusions of NE producing plasma levels of NE of up to approximately 3,000 pg/ml or plasma concentrations of NE at least threefold greater than present under most pathophysiological conditions and during acute activation of the sympathetic nervous system, there were no significant long-term changes in MAP or relative excretion rates of sodium and potassium from denervated and innervated kidneys. In marked contrast, pharmacological plasma levels of NE ( approximately 7,000 pg/ml) produced chronic increases in MAP (to 116 +/- 2% of control) and sustained reductions in Den/Inn for urinary sodium and potassium excretion to 57 +/- 4 and 68 +/- 5% of control, respectively, indicating a lower excretion rate of these electrolytes from denervated vs. innervated kidneys. We conclude that the chronically denervated kidney does not exhibit an exaggerated antinatriuretic response to either physiological or pathophysiological levels of circulating NE. It is therefore unlikely that renal denervation supersensitivity is a confounding issue in studies employing chronic renal denervation to elucidate the role of the renal nerves in the regulation of sodium excretion.

Animals↗

Effects of carotid and aortic chemoreceptor denervation in newborn piglets.

The objective of the present study was to test the hypothesis that in neonatal piglets there would be no hypoventilation after sham denervation or aortic denervation (AOD) alone, but there would be transient hypoventilation after carotid body denervation (CBD) and the hypoventilation would be greatest after combined carotid and aortic denervation (CBD+AOD). There was a significant (P < 0.05) hypoventilation in CBD and CBD+AOD piglets denervated at 5, 15, and 25 days of age. The hypoventilation in CBD+AOD piglets denervated at 5 days of age was greater (P < 0.05) than that of all other groups. Conversely, sham-denervated and AOD piglets did not hypoventilate after denervation. Injections of sodium cyanide showed that aortic chemoreceptors were a site of recovery of peripheral chemosensitivity after CBD. This aortic sodium cyanide response was abolished by prior injection of a serotonin 5a receptor blocker. Residual peripheral chemosensitivity after CBD+AOD was localized to the left ventricle. We conclude that 1) aortic chemoreceptors contribute to eupneic breathing in piglets that were carotid denervated at 5 days of age and 2) there are multiple sites of residual peripheral chemosensitivity after CBD.

Animals↗

Enlarged motor units resulting from partial denervation of cat hindlimb muscles.

1. It was the aim of this study to determine the extent to which a mammalian motoneuron can sprout in a partially denervated muscle, which motor unit types are involved in sprouting, and whether polyneuronal innervation exists between sprouted units. 2. The fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus were partially denervated by unilateral section of the L7 ventral root in 12-wk-old kittens. After approximately 100 days single motor units were isolated, and their isometric contractile characteristics were determined. FDL units were also tested for their resistance to fatigue and categorized as fast-twitch, fatiguing fibers (FF), fast-twitch, fatigue-resistant fibers (FR), and slow-twitch, fatigue-resistant fibers (S). The presence of polyneuronal innervation was investigated between pairs of like and unlike units. 3. The extent of the original denervation was variable and was estimated from the distribution of motor axons innervating the muscle via the L7 and S1 (soleus) or L6 and L7 (FDL) ventral roots on the contralateral side. In soleus, denervations ranged from 75 to 98%; in FDL, 60 to 97% (denervations less than 60% were not investigated). In general, motor-unit force increased in proportion to the extent of the denervation. 4. Within soleus, unit force increased to over 2 N, which was about 16 times greater than the average for a normal muscle (133 mN). However, most units increased in force to between five and 12 times normal. 5. Within FDL, the force development of type S units was unaffected by partial denervation. Type FF units increased by up to 11 times (4.3 N) compared with normal FF units (395 mN) with most increasing between two and four times. FR units exhibited the greatest relative increase in force [up to 19 times (4.3 N) compared with normal (225 mN)]. Most units were two to seven times the normal. 6. A few FDL units were glycogen depleted, the muscles frozen, and cross sections prepared for histochemical analysis. This indicated that the largest units contained approximately 5,000 fibers, and there was little fiber hypertrophy. In the extensively denervated soleus muscle, large numbers of small, presumably denervated fibers were observed. The innervation ratio of several large units was determined indirectly using mean fiber area. This gave estimates of 3,000-4,000 fibers for the largest units. Again, fiber hypertrophy contributed little to the increase in unit force. It was concluded that the increased force of units in both muscles was largely attributable to terminal and axonal sprouting of the intact motor axons. 7. No evidence for polyneuronal innervation was found in either FDL or soleus muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Renal denervation and sodium balance in young spontaneously hypertensive rats.

In 7-week-old male, spontaneously hypertensive rats (SHR) and matched normotensive control rats, Wistar Kyoto Rats (WKY), a bilateral renal denervation was performed. In two additional groups of rats a sham denervation was done (SHRS, WKYS). The animals were then kept in metabolic cages during a 10-day period during which sodium intake, urine volume, urinary sodium excretion, fecal sodium excretion, urinary aldosterone excretion and plasma renin activity were determined. Fractional urinary excretion of sodium was higher in the denervated SHR (p less than 0.1) and WKY (p less than 0.05) during the first 3 days after denervation, but during the following 3-day periods no difference between denervated and sham-operated groups was noted. The difference in fractional urinary excretion of sodium initially was due to a diminished urinary sodium excretion in the sham-operated groups since both SHRS and WKYS exhibited a significant increase between the first and the last 3-day period. Urine volume increased significantly in both SHR and WKY after denervation. Urinary aldosterone excretion on the 7th day after denervation was significantly lower in SHR compared to WKY, but there was no significant difference between the denervated and sham-operated groups. PRA was also significantly lower in SHR but no significant decrease was seen after denervation.

Aldosterone↗

Peripheral denervation suppresses the late phase of delayed-type hypersensitivity.

The impact of peripheral denervation on antigen-specific immune responses was analysed on the B and T cell levels. Delayed-type hypersensitivity (DTH) response to sheep red blood cells (SRBC) or oxazolone was used in mice as a model system of in vivo T cell reactivity. Serum antibody levels to SRBC, measured by an enzyme-linked immunosorbent assay (ELISA), were evaluated to analyse the B cell response. The effect of peripheral denervation on immune responsiveness was studied both at the point of sensitization and elicitation. The results show that peripheral denervation significantly suppresses the local DTH response. The late, inflammatory phase but not the early phase of the DTH reaction was reduced after denervation (p less than 0.01). The DTH suppression by denervation was similar irrespective of whether the neurectomy was performed 1 or 4 weeks prior to sensitisation. Even in the contralateral limb, with intact innervation, the inflammatory DTH reactivity was decreased. We believe that this phenomenon might be due to abrogation of the reflex arch since the denervation procedure did not give rise to a significant systemic downregulation of DTH. Also, peripheral denervation significantly suppressed footpad swelling induced by local administration of cholera toxin, a potent phlogistic compound. The antibody response against the same immunogen was not influenced by denervation. Our results suggest that denervation of a mixed peripheral sensory/motor nerve abrogates the formation of both T cell-dependent and independent inflammatory responses.

Animals↗

Changes of renal sympathetic activity in acute and chronic conscious sinoaortic denervated rats.

The arterial pressure level attained in sinoaortic denervated rats depends on the net effect of eliminating excitatory and inhibitory influences (chemoreceptor and baroreceptor elimination, respectively). After sinoaortic denervation is completed, the hypertension usually observed within the first few days is followed by normotension at the chronic stages. In this work renal sympathetic nerve activity was measured in conscious, unrestrained rats 6 hours (acute) and 20 days (chronic) after sinoaortic denervation. Increased arterial pressure (154 +/- 10 versus 114 +/- 3 mm Hg in controls) and renal sympathetic nerve activity (32 +/- 5 versus 13 +/- 2 bars per cycle in controls) with no changes in heart rate (404 +/- 17 vs 380 +/- 26 beats per minute) were observed in rats with acute sinoaortic denervation. In rats with chronic sinoaortic denervation, arterial pressure (119 +/- 8 mm Hg) and renal sympathetic nerve activity (13 +/- 6 bars per cycle) returned to control levels. Bradycardiac and tachycardiac responses to changes in blood pressure were reduced to 88% and 89%, respectively, in rats with acute sinoaortic denervation and 76% and 74%, respectively, in rats with chronic sinoaortic denervation. The reflex control of renal sympathetic nerve activity after acute and chronic sinoaortic denervation showed an impairment of sympathoinhibition (0.13 +/- 0.02 and 0.25 +/- 0.1 bars per cycle, respectively, versus 0.9 +/- 0.17 bars per cycle in controls). Sympathoexcitatory responses also were impaired in rats with acute and chronic sinoaortic denervation (0.08 +/- 0.03 and 0.37 +/- 0.1 bars per cycle, respectively, compared with 0.98 +/- 0.2 bars per cycle in controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Retardation of the development of hypertension in DOCA-salt rats by renal denervation.

To determine the importance of the renal nerves in DOCA-salt hypertension, either renal denervation or a sham-operation was carried out on both DOCA-salt-treated and non-DOCA-treated rats. The systolic blood pressure of the non-DOCA rats remained within normotensive levels, in which the difference in blood pressure levels between the renal denervated and the sham-operated groups was not significant. On the other hand, the blood pressure of the rats treated with DOCA, and having intact renal nerves, began to rise by the end of the first week and rose consistently thereafter, whereas, in the renal denervated DOCA-salt rats, the blood pressure started to rise by the second week and then proceeded to increase gradually. The differences between the sham and the denervated rat groups were significant throughout the four weeks. The mean arterial pressure, directly measured from the caudal artery of conscious rats during the fourth week of this study, was 166 +/- 7 mmHg in the sham-operated and 129 +/- 4 mmHg in the renal-denervated rats (the data having an 1% significant difference). To test the effects of renal denervation on the natriuresis, pentobarbital-anesthetized rats were infused intravenously with physiological saline. The renal denervated rats which had received DOCA excreted more sodium than did the sham-operated rats. When the rats were later anesthetized with urethane to allow intracisternal injections of hypertonic saline, the mean blood pressure in renal denervated rat groups was again lower than that of the sham-denervated rat groups. However, subsequent intracisternal injections of 5% saline produced similar pressor responses as well as tachycardia in both DOCA groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗