Effects of yohimbine on bradycardia and duration of recumbency in ketamine/xylazine anesthetized ferrets

Eleven adult ferrets (Mustela putorius furo) were anesthetized with ketamine hydrochloride (25 mg/kg, IM) and xylazine hydrochloride (2 mg/kg, IM). Fifteen minutes post-ketamine/xylazine injection, ferrets were treated with yohimbine hydrochloride at a dose of 0.5 mg/kg, or an equal volume of physiologic saline, intramuscularly. Each ferret served as its own control by randomly receiving both treatments with a minimum interval of 2 weeks between treatments on any one ferret. At 15 minutes post-ketamine/xylazine injection, mean heart rate measurements for both treatment groups were 27% less than the mean heart rate measurement reported for unanesthetized ferrets. Intramuscular administration of yohimbine antagonized the ketamine/xylazine induced bradycardia in 10 of the 11 ferrets, (p = 0.0001). In yohimbine treated ferrets, an increase in mean heart rate measurement was noted 5 minutes after the intramuscular administration of yohimbine, and followed, over the next 15 minutes, by a progressive increase in mean heart rate. However, a corresponding decrease in mean heart rate measurement was observed in saline treated controls. Fifteen minutes after the injection of yohimbine, the mean heart rate measurement of yohimbine treated animals had increased to 194 beats per minute. This mean heart rate measurement is nearly 30% greater than the mean heart rate of 150 beats per minute measured at 15 minutes post-saline injection in saline treated controls. Also, yohimbine treatment significantly reduced duration of recumbency in 10 of 11 ferrets (p = 0.0001). Mean duration of recumbency for yohimbine treated ferrets was 41 +/- 9.7 minutes, whereas mean duration of recumbency for saline treated ferrets was determined to be 80 +/- 11.4 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antagonism of xylazine hydrochloride-ketamine hydrochloride immobilization in guineafowl (Numida meleagris) by yohimbine hydrochloride

The mean time to arousal (MTA), the mean time to sternal recumbency (MTSR) and the mean time to walking (MTW) were measured in 10 adult guineafowl (Numida meleagris) immobilized with a combination of xylazine hydrochloride (1 mg/kg) and ketamine hydrochloride (25 mg/kg). Yohimbine hydrochloride, given intravenously (1 mg/kg) at 40 min after the injection of the xylazine-ketamine, significantly shortened the MTA, the MTSR and the MTW compared to saline controls. Increasing the dosage of yohimbine to 2.5 mg/kg did not shorten recovery when compared to the lower dosage. No adverse effects were noted at either dosage of yohimbine. Yohimbine appeared to be a safe and effective antagonist of xylazine-ketamine immobilization in guineafowl and may prove useful in other avian species to produce more rapid recovery from xylazine-ketamine immobilization, xylazine sedation or xylazine overdosage.     

Failure of yohimbine to reverse ketamine anesthesia in rhesus monkeys

Yohimbine hydrochloride has been used experimentally to reverse the anesthetic effects of ketamine and xylazine in dogs, cats, cattle and mule deer, but there are no reports of its use in nonhuman primates. Nine adult female rhesus monkeys were given an intravenous dose of either 0.5 mg/kg yohimbine hydrochloride or saline 10 minutes after intramuscular administration of 10 mg/kg ketamine hydrochloride. There was no difference in the duration of anesthesia between the yohimbine and saline treatments, suggesting yohimbine is not effective in the rhesus monkey.     

Immobilization of gray wolves (Canis lupus) with sufentanil citrate

Gray wolves (Canis lupus) were immobilized with 0.5 mg/kg xylazine plus 7.5 micrograms/kg of either sufentanil (n = 8), etorphine (n = 8), or carfentanil (n = 2). Drug doses used in this study were selected to provide consistency for comparison and are not recommended doses for effective immobilization of wolves. Induction times were similar among groups (11.9 +/- 1.0 min). Thirty min after induction, wolves were given either 0.5 mg/kg naloxone hydrochloride plus 0.15 mg/kg yohimbine hydrochloride or saline only intravenously. Arousal times for wolves given naloxone and yohimbine (1.2 +/- 0.1 min) were shorter than wolves given saline (35.5 +/- 6.4 min). Respiratory rates were similar among the three drug groups (6.9 +/- 1.0 breaths/min). One animal given sufentanil then saline was found dead 108 min after induction. Presumptive diagnosis was renarcotization and hypothermia. Results indicated that sufentanil is an effective opioid immobilizing agent for gray wolves.     

Antagonism of xylazine hydrochloride with yohimbine hydrochloride and 4-aminopyridine in captive wapiti

Eight captive wapiti (Cervus elaphus nelsoni) were injected with xylazine hydrochloride on two occasions during March and April 1984. Animals were grouped into a modified Latin square design and were given either successive injections of yohimbine hydrochloride and 4-aminopyridine (4-AP) to antagonize the sedative effects of xylazine hydrochloride or permitted an unantagonized recovery. Induction times ranged from 3 to 26 min with excited and wild animals requiring a supplementary dose. Time until walking was significantly (P less than 0.005) shorter in the group given successive injections (given i.v.) of the reversal drugs yohimbine hydrochloride (0.15 mg/kg) and 4-AP (0.30 mg/kg) than those animals during unantagonized recoveries. Marked increase in heart rate and respiratory rate were observed in animals within 3 min after successive injections of yohimbine hydrochloride and 4-AP. There was no occurrence of convulsions and animals did not relapse to profound sedation. Slight muscle tremors were observed in one animal which received a dose of 0.35 mg/kg of 4-AP. This drug combination can reduce markedly the duration of recovery from xylazine hydrochloride-induced sedation in wapiti.     

Muscle necrosis in Syrian hamsters resulting from intramuscular injections of ketamine and xylazine

To assess tissue damage resulting from intramuscular injection of mixtures of ketamine and xylazine, 48 hamsters were given 100, 150 or 200 mg/kg ketamine and 10 mg/kg xylazine in one hind leg and an equal volume of sterile physiologic saline in the other leg. Four hamsters from each group were killed 1, 3, 7 and 14 days after injection and the tissues at the injection sites were examined. There was grossly apparent muscle necrosis in most of the ketamine-xylazine injected legs. By light microscopy, 47 of 48 legs injected with ketamine-xylazine had moderate to extensive muscle necrosis with an acute to chronic inflammatory response, depending on the time elapsed since injection. Microscopic slides of the injection sites were coded, randomized and scored for severity of muscle lesions. Lesion scores for ketamine-xylazine injected legs were significantly higher than controls at all post-injection times. These findings indicate that intramuscular injection of ketamine with xylazine can cause extensive muscle necrosis in hamsters and should not be used for anesthesia in survival procedures.     

Yohimbine reversal of ketamine-xylazine immobilization of raccoons (Procyon lotor)

Six adult raccoons (Procyon lotor) were sedated with a combination of ketamine hydrochloride (KH) at 10 mg/kg body weight and xylazine hydrochloride (XH) at 2 mg/kg body weight intramuscularly (i.m.). Twenty min after the KH-XH combination was given, yohimbine hydrochloride (YH) at either 0.1 mg/kg (Trial 1) or 0.2 mg/kg (Trial 2) body weight or a saline control (Trial 3) was administered intravenously (i.v.). The time to arousal, time to sternal recumbency and time to walking were recorded. These times were significantly shortened after YH administration [e.g., mean time to walking (MTW) at 0.2 mg/kg YH = 23.7 min] as compared to the saline controls (MTW = 108.8 min). Heart and respiratory rates both increased after YH administration, while body temperature remained constant. A fourth trial was performed using a higher ratio of KH to XH (45:1 rather than 5:1) to mimic sedation as performed in the field. The mean time to arousal (MTA) and MTW in this trial (1.3 and 23.7 min, respectively) were significantly shorter than controls and similar to YH trials performed after immobilization with 5:1 KH-XH. Yohimbine hydrochloride may be useful in field studies that require sedation of raccoons using KH-XH combinations.     

Effect of caffeine sodium benzoate, ketamine hydrochloride, and yohimbine hydrochloride on xylazine hydrochloride-induced anorexia in white-tailed deer

Fifteen male white-tailed deer (Odocoileus virginianus) were administered xylazine hydrochloride (1 mg/kg BW i.m.), xylazine hydrochloride (1 mg/kg i.m.) followed by caffeine sodium benzoate (10 mg/kg i.m.), xylazine hydrochloride (0.5 mg/kg i.m.) and ketamine hydrochloride (4.5 mg/kg i.m.), and xylazine hydrochloride (1 mg/kg i.m.) followed by yohimbine hydrochloride (0.125 mg/kg i.m.), in a Latin Square design. Mean dry matter intake (DMI) for 4 days pre-treatment was compared to each of 4 days post-treatment. A significant (P less than 0.01) decrease in DMI was found only on the first day following treatment for each of the four drug combinations. The percent decreases in DMI on the first 24-hr period after immobilization were: xylazine hydrochloride 47%, xylazine hydrochloride/caffeine sodium benzoate 36%, xylazine hydrochloride/yohimbine hydrochloride 36%, and xylazine hydrochloride/ketamine hydrochloride 31%. The xylazine hydrochloride/ketamine hydrochloride combination was found to be insufficient to adequately sedate the deer. The use of caffeine or yohimbine hydrochloride is recommended to reduce recumbency time, but offers no improvement in xylazine hydrochloride-induced anorexia.     

A comparison of carfentanil/xylazine and Telazol/xylazine for immobilization of white-tailed deer

October 2001 to January 2002, captive free-ranging white-tailed deer (Odocoileus virginianus) were immobilized with a combination of carfentanil citrate and xylazine hydrochloride. From this study, we selected a dose of carfentanil/xylazine for the purpose of comparing immobilization parameters and physiologic effects with those of a combination of tiletamine and zolazepam (Telazol) and xylazine. Animals were initially given intramuscular injections of 10 mg xylazine and one of four doses of carfentanil (i.e., 0.5, 1.0, 1.5, and 2.0 mg). A carfentanil dose of 1.2 mg (x +/- SD = 23.5 +/- 3.2 microg/kg) and 10 mg xylazine (0.2 +/- 0.03 mg/kg) were selected, based on induction times and previously published reports, to compare with a combination of 230 mg of Telazol (4.5 +/- 0.6 mg/kg) and 120 mg xylazine (2.3 +/- 0.3 mg/kg). Time to first observable drug effects and to induction were significantly longer for deer treated with carfentanil/xylazine than with Telazol/xylazine (P < 0.01). Hyperthermia was common in deer immobilized with carfentanil/xylazine, but heart rate, respiration rate, and hemoglobin saturation were within acceptable levels. Degree of anesthesia of deer immobilized with Telazol/xylazine was superior to deer immobilized with carfentanil/xylazine. The combination of 120 mg of naltrexone hydrochloride and 6.5 mg of yohimbine hydrochloride provided rapid and complete reversal (1.9 +/- 1.1 min) of carfentanil/xylazine immobilization. Animals immobilized with Telazol/xylazine had long recovery times with occasional resedation after antagonism with 6.5 mg of yohimbine. The combination of carfentanil and xylazine at the doses tested did not provide reliable induction or immobilization of white-tailel (leer even though drug reversal was rapid and safe using naltrexone and yohimbine.     

Stimulation of either cholecystokinin receptor subtype reduces while antagonists potentiate or sensitize a morphine-induced excitatory response.

Cholecystokinin peptides (CCK) have been shown to antagonize many opioid-mediated effects. The present study was undertaken to determine whether peripheral injections of cholecystokinin sulphated octapeptide (CCK8), cholecystokinin tetrapeptide (CCK4), the CCK(1) (lorglumide) and the CCK(2) (PD-135,158 and LY-225910) receptor antagonists can influence a classic morphine excitatory effect, i.e. the display of Straub tail reaction in mice (STR). A total of 570 female Balb/C mice were tested. Experiment 1 was undertaken to determine whether i.p. injections of CCK8 or CCK4 can influence STR. Each animal was treated with i.p. injections of saline or CCK8 (10 and 20 nmol/kg) or CCK4 (20 and 40 nmol/kg). After 30 min all animals received an i.p. injection of morphine hydrochloride (10.0 mg/kg). The highest doses of both CCK8 (35% STR) and CCK4 (40% STR) significantly reduced STR as compared to saline (85% STR) treated mice (Fisher test; P < 0.01). In experiment 2 each animal was treated with ip injections of saline or 1.0 mg/kg lorglumide or PD-135,158 fifteen minutes before an injection of morphine at doses ranging from 1.0 to 50.0 mg/kg. In experiment 3 animals were treated with injections of saline, 0.1 or 10.0 mg/kg lorglumide or LY-225910 before an injection of a fixed MC dose (2.0 mg/kg). Both lorglumide and PD-135,158 induced a significant shift to the left in the morphine dose-response curves as well as a significant decrease in ED50 of the STR. ED50 for lorglumide was significantly lower than ED50 for PD-135,158. Both doses of lorglumide and the highest dose of LY-225910 significantly increased the percent of animals displaying STR. Experiment 4 was undertaken to determine whether repeated peripheral injections of morphine or the morphine-potentiating agents CCK(1) (lorglumide) and the CCK(2) (LY-225910) receptor antagonists can induce morphine sensitization. Each animal was treated with 5 daily i.p. injections of saline (control group), 1.5 mg/Kg morphine hydrochloride (group morphine), and 1.0 mg/Kg lorglumide (group LOR) or LY-225910 (group LY). One, two, three and four weeks after the last treatment day, all animals were challenged with one i.p. injection of morphine (1.5 mg/Kg). The morphine, LOR groups and group LY showed a significant increase in percentage of animals displaying STR. These data demonstrate that the blockade of endogenous CCK actions leads to morphine sensitization probably through both CCK receptors. The present data are consistent with the antagonistic effects of CCK and opioids in the control of morphine-induced STR. In addition, these results suggest that both CCK receptors are involved in the modulatory effects of CCK on this morphine effect.     

Physiological response of gray wolves to butorphanol-xylazine immobilization and antagonism by naloxone and yohimbine

Captive gray wolves (Canis lupus) were immobilized (loss of consciousness) with 2.0 mg/kg xylazine hydrochloride (XYL) and 0.4 mg/kg butorphanol tartrate (BUT) administered intramuscularly. Induction time was 11.8 +/- 0.8 min (mean +/- SE). Immobilization resulted in bradycardia, respiratory depression, and normotension. Fifteen min after induction, six wolves were given either 0.05 mg/kg naloxone hydrochloride (NAL) and 0.125 or 0.250 mg/kg yohimbine hydrochloride (YOH), or an equal volume of saline (control) intravenously. Antagonism resulted in shortened recovery times compared to control animals (P less than 0.03); there was no difference in recovery times between the YOH doses (P greater than 0.05). Antagonism caused increases in heart rate (HR) and respiratory rate (RR), but no changes in MABP. Eight other wolves were similarly immobilized, but given only NAL. This resulted in partial antagonism with the animals appearing to be sedated with XYL only. Three wolves given only 0.4 mg/kg BUT assumed a state described as "apathetic sedation." Three other wolves sedated with only 2.0 mg/kg XYL showed a profound sedation characterized by recumbency, bradycardia and shallow, but regular, respiration. This study demonstrated that (1) BUT and XYL together, but not separately, can completely immobilize wolves, (2) this combination can be rapidly antagonized by NAL and YOH, and (3) there appeared to be no adverse cardiopulmonary reactions to any of the drugs used.     

Antagonism of xylazine hydrochloride sedation in raptors by yohimbine hydrochloride

The mean time to initial reversal response (MTIRR) and the mean time to perching (MTP) were measured in 34 raptors sedated with xylazine hydrochloride with dosages ranging from 1.0 to 20 mg/kg intravenously (i.v.) and 2.5 to 20.0 mg/kg intramuscularly (i.m.). Yohimbine hydrochloride, given i.v. (0.2 mg/kg), 30 min after the injection of the xylazine, shortened the MTIRR and MTP compared to the controls. No adverse effects were noted due to the use of yohimbine. Yohimbine appeared to be a safe and effective antagonist for xylazine sedation in raptors.     

The effects of prolonged ketamine-xylazine intravenous infusion on arterial blood pH, blood gases, mean arterial blood pressure, heart and respiratory rates, rectal temperature and reflexes in the rabbit

The prolonged and safe maintenance of general anesthesia in rabbits with commonly used injectable agents is difficult. Protracted, stable anesthesia with short recovery time has been described in humans using continuous intravenous infusion of ketamine with or without sedatives, muscle relaxants and paralytics. This study evaluated the anesthetic plane achieved and respiratory and cardiovascular effects produced with a ketamine-xylazine intravenous infusion in New Zealand White rabbits. Ten female rabbits were anesthetized with intramuscularly administered ketamine hydrochloride (35 mg/kg) and xylazine hydrochloride (5 mg/kg) after the preanesthetic, baseline measurements of arterial blood pO2, pCO2 and pH and heart and respiratory rates were recorded. The above parameters as well as mean arterial blood pressure, righting, palpebral, pedal, and jaw reflexes were monitored ten minutes after the intramuscularly administered dosage and throughout 4 hours of infusion. Results showed moderate hypotension (21.2% deviation from normal, p less than 0.008) and profound hypoxemia (45% deviation from baseline, p less than 0.001) 10 minutes after the intramuscularly administered induction dosage. Then, the 4 hour infusion of ketamine (1 mg/minute) and xylazine (0.1 mg/minute) was started. Hypotension progressed (49.1% deviation from normal, p less than 0.008), but hypoxemia and hypercarbemia gradually improved with no resultant change (p greater than 0.1) in arterial pH. There was no significant change (p greater than 0.1) in respiratory rate but varying qualities of respiration were observed. Both mean arterial pO2 and pCO2 values returned to baseline within 20 minutes after completion of infusion. Heart rate and rectal temperature remained stable during the trial. The righting reflex was abolished in all rabbits throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pre-electroconvulsive shock administration of calcium channel blockers reduces retrograde amnesia induced by ECS

Effect of pre-electroconvulsive shock (ECS) administration of calcium channel blockers (CCBs) like verapamil, diltiazem, nifedipine, nimodipine, flunarizine and cinnarizine on retrograde amnesia induced by ECS was examined using passive avoidance paradigm in rats. The groups (Gr 1-7) of adult, male Wistar rats received true ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; ip) and other groups (Gr 8-14) received sham ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; i.p). The anti-amnestic activity of CCBs were evaluated using the passive avoidance paradigm in rats. Results showed that, the baseline latencies for all the groups did not differ significantly. Rats receiving true ECS produced significantly lower latencies. There was increase in the post ECS step through latencies of the rats administered CCBs before ECS. Therefore, pre-ECS administration of calcium channel blockers might reduce retrograde amnesia produced by ECS without altering seizure duration.     

Xylazine hydrochloride-ketamine hydrochloride immobilization of free-living red foxes (Vulpes vulpes) in Spain.

A combination of xylazine hydrochloride-ketamine hydrochloride was used to immobilize 83 wild red foxes (Vulpes vulpes) (15 pups and 68 adults) at Do?ana National Park (Spain). Mean ketamine hydrochloride doses were 17.1 mg/kg (SE = 1.53) and 12.3 mg/kg (SE = 0.4) for pups and adults, respectively, and mean xylazine hydrochloride doses for the same groups were 6.2 mg/kg (SE = 0.63) and 4.7 mg/kg (SE = 0.14), respectively. Mean induction times and first reaction times were 1.6 minutes and 22.5 minutes for pups and 3.8 minutes and 39.4 minutes for adults, respectively. Recommended doses for wild adult foxes of unknown weight are 75 mg of ketamine hydrochloride and 20 mg of xylazine hydrochloride.     

Differential depressant effects of general anesthetics on the cardiovascular response to cocaine in mice.

In recent years, murine models have gained increasing importance for studies of cardiovascular physiology and pharmacology, largely due to the development of transgenic strains with specific alterations in phenotype. Differential effects of general anesthetic agents on the cardiovascular responses to cocaine have been reported in larger mammals; therefore, we studied the effects of commonly used anesthetics on heart function and on blood pressure responses to cocaine in Swiss Webster mice. We positioned a polyethylene catheter (PE-10) in the right carotid artery or left ventricle of mice anesthetized with equivalent anesthetic dose of either ketamine-xylazine (KX, 40 mg/kg + 5 mg/kg), pentobarbital (PEN, 40 mg/kg) or alpha-chloralose-urethane (CU, 80 mg/kg + 100 mg/kg). Cocaine (0.3 mg/kg, 1 mg/kg and 3 mg/kg) was administrated via the left jugular vein by bolus injection. In the KX group, the basal mean arterial pressure (MAP) and systolic left ventricular pressure (LVP) were 110 +/- 12 and 120 +/- 13 mmHg, respectively, close to conscious values. However, PEN and CU significantly decreased the basal parameters (P < 0.01 compared to the KX group). The lowest dose of cocaine (0.3 mg/kg) elicited minimal changes. Significant responses were obtained with a 1-mg/kg dose of cocaine (P < 0.01 compared to baseline). However, at 3 mg/kg, a toxic effect of cocaine appeared in all three anesthetic groups. Compared to published conscious animal data, anesthetic agents attenuated the cardiovascular effects of cocaine. Taken together, our results indicate that minimally effective doses of general anesthetics may significantly alter the basal hemodynamic state and the responses to sympathomimetic agents in the murine model, as has been reported in larger mammalian species. We concluded that anesthesia with ketamine-xylazine provides baseline hemodynamic values close to reported values in conscious animals, but also attenuates the hemodynamic response to cocaine.     

Chemical immobilization of red foxes (Vulpes vulpes)

Red foxes (Vulpes vulpes) were immobilized with one of the following drug combinations: ketamine/xylazine (n = 22), ketamine/promazine (n = 35), ketamine/midazolam (n = 13), or tiletamine/zolazepam (n = 22). Foxes given ketamine/xylazine had the shortest induction and longest recovery times relative to other drug combinations, whereas foxes given ketamine/midazolam had the longest induction times. Recommended doses for the various combinations are given. Foxes given ketamine/xylazine were given either 0.1, 0.2, 0.4 mg/kg yohimbine, or saline 40 min after anesthetic induction. Administration of yohimbine significantly shortened arousal and recovery times relative to control values (P less than 0.001).     

Nimodipine's interactions with other drugs: II. Diazepam

Adult Binghamton Heterogeneous (HET) stock mice were administered one of three doses of diazepam (0.1, 2.5, or 5.0 mg/kg) immediately followed by a second injection of either the slow calcium channel blocker, nimodipine (Bay e 9736), or its vehicle. Hypothermic responses and muscular incoordination were measured twenty and sixty minutes later as assessed by changes in rectal temperature and motoric activity on a rotating rod. Nimodipine (5 mg/kg) alone did not significantly affect body temperature or motor coordination. However, when administered in combination with the two highest doses of diazepam, nimodipine significantly potentiated the hypothermic response produced by these doses both twenty minutes and sixty minutes post-injection. Administration of high doses of diazepam (2.5 and 5.0 mg/kg) resulted in significant motor incoordination at both observation periods, but this effect was not potentiated by nimodipine.     

Sex chromosome complement affects nociception in tests of acute and chronic exposure to morphine in mice

We tested the role of sex chromosome complement and gonadal hormones in sex differences in several different paradigms measuring nociception and opioid analgesia using "four core genotypes" C57BL/6J mice. The genotypes include XX and XY gonadal males, and XX and XY gonadal females. Adult mice were gonadectomized and tested 3-4 weeks later, so that differences between sexes (mice with testes vs. ovaries) were attributable mainly to organizational effects of gonadal hormones, whereas differences between XX and XY mice were attributable to their complement of sex chromosomes. In Experiment 1 (hotplate test of acute morphine analgesia), XX mice of both gonadal sexes had significantly shorter hotplate baseline latencies prior to morphine than XY mice. In Experiment 2 (test of development of tolerance to morphine), mice were injected twice daily with 10 mg/kg morphine or saline for 6 days. Saline or the competitive NMDA antagonist CPP (3-(2-carboxypiperazin-4yl) propyl-1-phosphonic acid) (10 mg/kg) was co-injected. On day 7, mice were tested for hotplate latencies before and after administration of a challenge dose of morphine (10 mg/kg). XX mice showed shorter hotplate latencies than XY mice at baseline, and the XX-XY difference was greater following morphine. In Experiment 3, mice were injected with morphine (10 mg/kg) or saline, 15 min before intraplantar injection of formalin (5%/25 microl). XX mice licked their hindpaw more than XY mice within 5 min of formalin injection. The results indicate that X- or Y-linked genes have direct effects, not mediated by gonadal secretions, on sex differences in two different types of acute nociception.     

Role of intrarenal alpha(2)-adrenoceptors in the renal responses to xylazine in rats

This study examined the contribution of intrarenal alpha(2)-adrenoceptor mechanisms to the enhanced urine flow rate (V) and urinary sodium excretion (U(Na)V) responses in ketamine-xylazine-anesthetized rats. Ten minutes after left renal artery (LRA) injection, the alpha(2)-adrenoceptor antagonist yohimbine (5 microg) significantly decreased V from 58 +/- 8 to 35 +/- 7 microl. min(-1). g kidney wt(-1) and U(Na)V from 2.8 +/- 0.4 to 2.1 +/- 0.4 microeq. min(-1). g kidney wt(-1) without altering right kidney function. The renal effects of the LRA injection of yohimbine were completely abolished in chronic bilaterally renal-denervated (RDNX) rats. In RDNX rats, a higher LRA dose of yohimbine (15 microg) significantly reduced left and right kidney V, with no effects on U(Na)V. In separate bladder-catheterized rats, yohimbine (0.5 mg/kg), 20 min after intravenous injection, significantly decreased V from 63 +/- 9 to 13 +/- 2 microl. min(-1). g kidney wt(-1 )and U(Na)V from 4.5 +/- 0.5 to 1.1 +/- 0.1 microeq. min(-1). g kidney wt(-1). In RDNX rats, this dose of yohimbine reduced V and U(Na)V, but the magnitude was blunted compared with intact rats. In contrast, 0.1 mg/kg iv yohimbine significantly reduced V and U(Na)V to similar magnitudes in intact and RDNX groups. Together, these findings indicate that intravenous xylazine acts by renal nerve-dependent and -independent mechanisms to enhance renal excretory function in ketamine-anesthetized rats. Because the effects of the LRA dose of yohimbine were abolished in renal-denervated animals, it appears that xylazine has a direct renal action to augment the renal excretion of water and sodium via a presynaptic alpha(2)-adrenoceptor pathway that inhibits the release of neurotransmitters from renal sympathetic nerve terminals.