Effects of ether and pentobarbital anesthesia on thyroid function in the rat.

Studies were performed to examine the effect of two anesthetic agents, ether and pentobarbital, on the hypothalamic-pituitary-thyroid function in vivo. In non-anesthetized animals, plasma thyrotropin (TSH) increased rapidly from basal values of 0.1, a peak of 0.49 microng/ml, 25 min after exposure to the cold. Anesthesia with ether during exposure to the cold completely prevented the rise in TSH. During pentobarbital anesthesia, the rise in TSH after exposure to cold was reduced by more than 90%. Even a three minute period of ether anesthesia prior to cold exposure reduced the peak response to cold as well as delayed this response when compared to the untreated group. During two hours of anesthesia with ether, the TSH concentration declined in animals which were fed a low iodine diet at essentially the same rate as in animals on the same diet given an injection of 3 microng of triiodothyronine. Pentobarbital did not suppress TSH at room temperature. The release of thyrotropin after injection of synthetic thyrotropin-releasing hormone (TRH) was greater in animals anesthetized with pentobarbital than in controls and was slightly reduced in ether-anesthetized animals. This difference was observed when thyrotropin was given intraperitoneally or intravenously and the slope of the dose-response curves to TRH showed a flattening of the curve of rats treated with ether and a steeper slope of response in animals anesthetized with pentobarbital. We conclude that pentobarbital inhibited TSH response to cold but did not reduce the resting levels. Ether inhibited the rise of TSH in the cold and lowered the basal levels of TSH in animlas at room temperature. Pentobarbital increased the response to TRH and ether may have reduced the response to TRH.     

Cardiovascular effects of cocaine in anesthetized and conscious rats

This study examined the cardiovascular and respiratory effects of cocaine and procaine in anesthetized and conscious rats. Intravenous cocaine (0.16-5 mg/Kg) elicited a rapid, dose dependent increase in mean arterial pressure of relatively short duration. In pentobarbital anesthetized (65 mg/Kg, i.p.) animals, the pressor phase was generally followed by a more prolonged depressor phase. These effects on arterial pressure were generally accompanied by a significant tachypnea and at larger doses (2.5 and 5 mg/Kg, i.v.), bradycardia. Procaine (0.31 and 1.25 mg/Kg, i.v.) produced similar cardiovascular and respiratory effects (depressor phase, tachypnea) in pentobarbital anesthetized animals. In conscious-restrained animals, both cocaine and procaine (1.25 mg/kg, i.v.) produced pressor responses. The subsequent depressor response was, however, absent in both cases. The cardiovascular effects of cocaine (0.25-1 mg/Kg, i.v.) in urethane anesthetized (1.25 g/Kg, i.p.) animals were essentially similar to those observed in conscious animals. Procaine (1mg/Kg) did not produce any significant cardiovascular effects in urethane anesthetized animals, but did elicit tachypnea. Reserpine pretreatment (10 mg/Kg, i.p.) did not significantly attenuate the pressor response in urethane anesthetized animals. Phentolamine pretreatment (3 mg/Kg, i.v.) did significantly antagonize the pressor effect in urethane anesthetized animals. These results suggest that: the depressor phase is likely due to a interaction between local anesthetic activity (cocaine and procaine) and barbiturate anesthesia, the cardiovascular effects of cocaine in conscious animals are more similar to those observed in urethane anesthetized rats than in pentobarbital anesthetized rats and the pressor effect in urethane anesthetized rats is apparently due to a reserpine resistant catecholaminergic mechanism.     

A time-course study of the effects of pentobarbital, fentanyl, and morphine chloralose on myocardial mechanics.

Cardiovascular physiological studies in anesthetized animals may be confounded by the hemodynamic actions of the anesthetic agents themselves. To identify an anesthetic regimen that does not significantly influence cardiovascular physiology, the hemodynamic responses of 28 dogs were studied. Animals were equally divided among groups with 1) no anesthesia (i.e., trained conscious preparation), 2) pentobarbital sodium, 3) fentanyl citrate, and 4) a combination of morphine sulfate and alpha-chloralose. Anesthesia was maintained for 3 h. Data were acquired with the use of ultrasound imaging of the heart in conjunction with invasive pressure measurements. Left ventricular ejection phase indexes and end-systolic force-velocity relations were used to evaluate the effects of each anesthetic agent on overall systolic performance and myocardial contractility. Compared with the conscious animals, pentobarbital profoundly depressed systolic performance (P less than 0.05 vs. control) because of a reduction in myocardial contractility (P less than 0.01) and an increase in left ventricular afterload (end-systolic wall stress, P less than 0.05). Fentanyl increased myocardial contractility (P less than 0.05) but also tended to increase afterload with the net result that overall systolic performance remained unchanged. Morphine-chloralose did not affect overall ventricular systolic performance or its individual determinants. Pentobarbital and fentanyl also caused progressive time-dependent deteriorations in all parameters of systolic function during prolonged anesthesia. In contrast, cardiac function was stable for greater than or equal to 3 h after induction of morphine-chloralose anesthesia. The hemodynamic profile of dogs anesthetized with morphine-chloralose most closely resembled that of the conscious animals. Morphine-chloralose is recommended when prolonged anesthesia is required for studies of cardiovascular physiology.     

Effect of the method of blood extraction on plasma levels of renin in the Wistar rat

To investigate the influence of blood extraction conditions on the renin-angiotensin system in rats, plasma renin activity (PRA) and plasma renin concentration (PRC) were measured in blood samples obtained by different methods. PRA and PRC in samples obtained by chronic catheterization, cardiac puncture without anesthesia, and decapitation immediately following light ether anesthesia were not significantly different from those obtained by simple decapitation (control group). In contrast, PRA and PRC in samples obtained by cardiac puncture and cavernous sinus puncture after light ether anesthesia were significantly (p less than 0.01) higher than those obtained in the control group. There was a significant direct correlationship between PRA and PRC in all samples studied (r = 0.87, p less than 0.001). The present results suggest that light ether anesthesia increases renin levels, except when blood samples are taken by decapitation, and that chronic catheterization and cardiac puncture are the choice blood extraction methods to evaluate the renin-angiotensin system in rats.     

Pituitary LH response to LHRH in male rats following pentobarbital anesthesia

Plasma LH concentrations were determined in unanesthetized or pentobarbital (PB) anesthetized male rats following several doses of LHRH administered into the lateral ventricle of jugular vein. Regardless of the route of injection of LHRH, plasma LH concentrations were similar whether animals received PB anesthesia or not. No evidence was found that PB enhanced or diminished the response of the pituitary to LHRH in male rats.     

山羊单纯与复合全身麻醉效果的比较

目的对比山羊单纯麻醉与复合麻醉的效果,探讨一种安全高效便捷的山羊麻醉方法。方法选取山羊30只,随机分为A、B、C三组,A组给予单纯戊巴比妥钠麻醉,B组给予单纯氯胺酮麻醉,C组给予地西泮、戊巴比妥钠和氯胺酮复合麻醉,记录三种麻醉方法的起效时间、麻醉维持时间、麻醉药物用量及麻醉死亡率。结果地西泮、戊巴比妥钠和氯胺酮复合麻醉,起效快、麻醉维持时间长、动物死亡率低、麻醉效果好。结论安定、戊巴比妥钠和氯胺酮复合麻醉优于单纯麻醉,是一种高效、便捷、安全山羊全身麻醉方法。     

Anesthetic dependence of the inhibitory effect of neurotensin on pentagastrin-stimulated acid secretion in rats. A possible role for somatostatin.

The existence of possible local mediators of the inhibitory effect of neurotensin on gastric acid secretion has not been determined. We perfused rats intragastrically with warmed saline and stimulated acid secretion with intravenous pentagastrin, 32 micrograms/kg/hr, and found that anesthesia with pentobarbital resulted in marked inhibition of acid secretion by intravenous neurotensin; however, anesthesia with urethane prevented this inhibitory effect of neurotensin from occurring. In addition, we found a significant increase in somatostatin-like immunoreactivity in portal venous blood during neurotensin infusion in pentobarbital-anesthetized rats. Neither neurotensin nor pentagastrin infusion modified gastric luminal somatostatin-like immunoreactivity after either pentobarbital or urethane, and rats anesthetized with urethane did not show an increase of somatostatin-like immunoreactivity in portal venous blood during neurotensin infusion. These results suggested that somatostatin-like immunoreactivity, released into the portal circulation, was necessary for exogenous neurotensin to inhibit pentagastrin-stimulated gastric acid secretion under these conditions in anesthetized rats.     

Lack of prostaglandin effect on sodium balance and hyperreninemia in adrenalectomized rats.

Glucocorticoids are known inhibitors of prostaglandin production. Prostaglandin E2 (PGE2) and prostacyclin (PGI2) are promoters of natriuresis and renin release. Excessive prostaglandin production, therefore, might contribute to the altered sodium balance and renin release observed in primary adrenal insufficiency. To test this hypothesis, sodium balance and prostaglandin production were measured in adrenalectomized rats and in animals receiving prostaglandin inhibitors or replacement dexamethasone. Compared to sham-operated controls, adrenalectomized rats had decreased two-day sodium balance and elevated plasma renin concentration (PRC), renal PGE2 production, and renal 6-ketoprostaglandin F1 alpha (6kPGF1 alpha, the nonenzymatic metabolite of PGI2); however, no appreciable change in aortic 6kPGF1 alpha production was observed. Dexamethasone given to adrenalectomized rats normalized PRC but had no effect on sodium balance or prostaglandin production. Likewise, prostaglandin inhibitors did not alter the sodium balance or decrease the PRC post adrenalectomy. These data confirm renal prostaglandin production is increased in adrenalectomized rats, but suggest that the elevation is not due directly to glucocorticoid deficiency. Further, PRC levels in adrenal insufficiency do not appear to be prostaglandin mediated. In conclusion, excessive renal prostaglandin production does not contribute to altered sodium balance or increased PRC in adrenalectomized rats.     

Pharmacological evidence for involvement of the sympathetic nervous system in the increase in renin secretion produced by a low sodium diet in rats

To determine the degree to which increased sympathetic activity contributes to the increase in renin secretion produced by a low sodium diet, the beta-adrenergic blocking drug propranolol or saline vehicle was injected through indwelling jugular cannulas in rats fed a normal diet and rats fed a low sodium diet for 9 days. Plasma renin activity (PRA) and plasma renin concentration (PRC) were elevated by the low sodium diet, and these values were reduced 42-45% by propranolol, although they were still higher than in the normal diet controls. Plasma corticosterone was moderately elevated in cannulated rats on regular diet, compared to decapitated controls, but corticosterone did not differ between cannulated and decapitated rats on low salt diet; propranolol reduced plasma corticosterone. However, PRA and PRC were comparable in cannulated rats and decapitated controls on both the normal and the low sodium diets, and propranolol did not produce a significant reduction in PRA and PRC in rats fed the normal diet. This indicates that the effects of propranolol on PRA and PRC in the low sodium rats were not simply due to reduction of a stress-induced increase in renin secretion. The results indicate that increased sympathetic activity makes a substantial contribution to the increase in renin secretion produced by 9 days of dietary sodium restriction.     

Recovery rate of the cardiovascular system in rabbits following short-term halothane anesthesia.

Mean arterial pressure, cardiac output and heart rate were determined in eight male New Zealand white rabbits while conscious and after being anesthetized with halothane plus nitrous oxide for 15 minutes. Delivery of the anesthetic agent was stopped and the measurement repeated at 15, 30, 60 and 210 minutes. In a separate experiment blood samples were obtained for plasma renin activity in six rabbits before anesthesia, after 15 minutes of halothane plus nitrous oxide administration, and again 210 minutes after cessation of the anesthesia. Later, this experiment was repeated with the same rabbits except that they were allowed to breathe room air instead of the anesthesia. The halothane anesthesia resulted in decreased mean arterial pressure and cardiac output, but these returned to the preanesthetic levels by 15 minutes after stopping the anesthesia. Heart rate increased during halothane administration, and although it tended to return toward control levels after cessation of the halothane, heart rate was still elevated 210 minutes later. Halothane plus nitrous oxide produced an increase in plasma renin activity, which then subsided to normal by 210 minutes following anesthesia; breathing room air did not result in increases in plasma renin activity. These studies revealed that although short-term anesthesia with halothane plus nitrous oxide resulted in cardiovascular changes in rabbits, after cessation of the anesthetic agent the cardiovascular system quickly returned to normal.     

Effects of decapitation, ether and pentobarbital on guanosine 3′,5′-phosphate and adenosine 3′,5′-phosphate levels in rat tissues

Cyclic GMP and cyclic AMP levels in eight different rat tissues were examined after animlas were immersed in liquid nitrogen. In order of decreasing concentration, cerebellu, kidney, lung and cerebral cortex contained the greatest quantities fo cyclic GMP. These tissues also contained relatively high concentrations of cyclic AMP. Compared to values in animals which were sacrificed in liquid nitrogen, levels of both nucleotides in many of the tissues examined were altered by decapitation or anesthesia with ether and pentobarbital. Decapitation increased the levels of both cyclic GMP and cyclic AMP in cerebellum, lung, heart, liver and skeletabl muscle. However, decapitation increased only cyclic AMP in cerebral cortex and kidney. Our previously reported high level of cyclic GMP in lung was attributed to ether anesthesia and surgical removal which increased the cyclic GMP content in lung, heart, testis and skeletal muscle. The effect of ether on cyclic GMP levels in lung and heart was blocked by pretreatment of animals with atropine which indicated that cholinergic agents increase cyclic GMP content in these tissues. Acetylcholine and carbachol in the presence of theophylline increased the accumulation of cyclic GMP in incubations of rat lung minces. Increases in cyclic GMP and cyclic AMP levels in cerebellum with ether anesthesia were prevented if rats were immersed in liquid nitrogen after anesthesis with ether. Anesthesia with pentobarbital decreased the levels of cyclic GMP in cerebellum and kidney and increased the nucleotide in heart, liver, testis and skeletal muscle compared to levels in tissues from animals immersed in liquid nitrogen. However, pentobarbital increased cyclic AMP levels in cerebellum and cerebral cortex and decreased the nucleotide in liver, kidney, testis and skeletal muscle. These studies provide a possible explanation for the variability in in vivo levels of cyclic GMP and cyclic AMP which have been previously reported. In addition, these studies support the hypothesis that the synthesis and degradation of cyclic AMP and cyclic GMP are regulated independently and not necessarily in a parallel or reciprocal manner. These studies also suggest that the increase accumulation of one cyclic nucleotide has no major effect on the synthesis and/or metabolism of the other; however, such interactions cannot be entirely excluded from the results of this study.     

Simultaneous elevation of plasma insulin and catecholamines during endotoxicosis in the conscious and anesthetized rat

Plasma levels of glucose, insulin and catecholamines were assessed during the early phase of sub-lethal endotoxicosis in fasted male rats which were either conscious or continuously anesthetized with sodium pentobarbital. Exogenous glucose challenge was administered during endotoxicosis to probe insulin release at a time when plasma catecholamines were elevated. An endogenous hyperglycemia occurred following endotoxin but was moderated by continuous pentobarbital anesthesia. Plasma insulin was elevated in the conscious but not anesthetized rats during endogenous hyperglycemia following endotoxin. Hyperglycemia with exogenous glucose elevated plasma insulin levels in both conscious and anesthetized groups and occurred in the presence of elevated levels of norepinephrine, epinephrine and dopamine. Simultaneous elevation of plasma catecholamine and insulin levels during endotoxicosis suggests that glucose utilization may be promoted at the same time that glucose is mobilized through adrenergic mechanisms. These events may contribute to the rapid depletion of carbohydrate stores leading to the hypoglycemia of the agonal stage of endotoxic shock.     

Quantitative changes in rat renin secretory granules after acute and chronic stimulation of the renin system

In order to study the cellular mode of renin secretion, stereological methods were used to estimate number and volume of rat renin secretory granules during stimulation of the renin system. An acute decrease in renal perfusion pressure to 40 mmHg for 5 min increased plasma renin concentration (PRC) twofold, but did not significantly change the number of renin granules per arteriole or the renin-containing volume of the arteriole. Chronic stimulation was achieved by a combination of low-salt diet and inhibition of angiotensin-converting enzyme (ACE) for 14 days, and resulted in a 36-fold increase in PRC, a 20-fold increase in the number of granules per arteriole, and a 17-fold increase in the arteriolar volume that contained renin. An acute decrease in renal perfusion pressure to 40 mmHg for 5 min in the chronically stimulated rats increased PRC further (1.6-fold), and significantly reduced the number of granules per arteriole by 4000 (45% reduction), but did not change the renin-containing arteriolar volume significantly. The average renin granule size was 0.35 μm³ with no significant differences among the groups. We conclude that recruited granular cells contribute significantly to renin release, and that all granular cells along the arteriole participate in secretory responses. The reduced number of renin granules after acute stimulation is compatible with exocytosis as the dominating mechanism of renin release.     

Comparative stability of physiological parameters during sustained anesthesia in rats

Rats were anesthetized with pentobarbital, pentobarbital and atropine, inactin [5-ethyl-5-(1'-methyl-propyl)-2-thiobarbiturate], ether and inactin, or urethane. Cardiovascular and arterial acid-base parameters were monitored over a 3-hour period of anesthesia. Heart rate, arterial pressures, and pH progressively decreased with duration of pentobarbital anesthesia. Changes observed in rats anesthetized with the thiobarbiturate, inactin, were similar although generally less severe. Most subjects treated with the barbiturates were markedly hypercapnic. Urethane anesthesia was characterized by a higher and more stable heart rate and greater pulse pressure. Arterial carbon dioxide and bicarbonate levels in the urethane group were substantially lower at all sampling times than the values obtained in the barbiturate groups.     

Effects of sodium pentobarbital anesthesia on blood flow in skin, myocutaneous, and fasciocutaneous flaps in swine.

Drug effect on flap blood flow is most commonly determined in anesthetized animals, yet the effect of the anesthetic is often poorly understood. Halothane and nitrous oxide cause profound changes in skin blood flow and thus provide an unsuitable anesthetic technique for use in measuring drug effects on skin and myocutaneous flaps in swine. The goal of this study was to determine the effects of sodium pentobarbital anesthesia on cardiovascular parameters and blood flow in skin, myocutaneous, and fasciocutaneous flaps in pigs. In seven pigs, 7 forelimb skin flaps, 7 forelimb fasciocutaneous flaps, 14 arterial buttock flaps, and 14 latissimus dorsi flaps were created. Blood flow was measured at 2-cm intervals along each flap while the animal was awake and anesthetized. A cardiac depressant effect of pentobarbital was observed, but no change in blood flow could be demonstrated in control skin or control muscle. However, pentobarbital did significantly increase blood flow in all viable portions of arterial and random skin flaps, fasciocutaneous flaps, and the cutaneous segments of the latissimus dorsi flap. These demonstrated effects of pentobarbital should be taken into consideration in designing and analyzing studies of flap blood flow in the acute postoperative phase.     

Increased expression of cyclooxygenase 2 contributes to aberrant renin production in connexin 40-deficient kidneys

We previously found that deletion of connexin 40 (Cx40) causes a misdirection of renin-expressing cells from the media layer of afferent arterioles to the perivascular tissue, extraglomerular mesangium, and periglomerular and peritubular interstitium. The mechanisms underlying this aberrant renin expression are unknown. Here, we questioned the relevance of cyclooxygenase-2 (COX-2) activity for aberrant renin expression in Cx40-deficient kidneys. We found that COX-2 mRNA levels were increased three-fold in the renal cortex of Cx40-deficient kidneys relative to wild-type (wt) kidneys. In wt kidneys, COX-2 immunoreactivity was minimally detected in the juxtaglomerular region, but renin expression was frequently associated with COX-2 immunoreactivity in Cx40-deficient kidneys. Treatment with COX-2 inhibitors for 1 wk lowered renin mRNA levels in wt kidneys by about 40%. In Cx40-deficient kidneys, basal renin mRNA levels were increased two-fold relative to wt kidneys, and these elevated mRNA levels were reduced to levels of untreated wt mice by COX-2 inhibitors. In parallel, renin immunoreactive areas were clearly reduced by COX-2 inhibitors such that renin expression vanished and decreased significantly in the periglomerular and peritubular extensions. Notably, COX-2 inhibitor treatment lowered plasma renin concentration (PRC) in wt kidneys by about 40% but did not affect the highly elevated PRC levels in Cx40-deficient mice. These findings suggest that aberrant renin-producing cells in Cx40-deficient kidneys express significant amounts of COX-2, which contribute to renin expression in these cells, in particular, those in the periglomerular and peritubular position. Apparently, these disseminated cells do not contribute to the enhanced renin secretion rates of Cx40-deficient kidneys.     

Muscle mechanosensitive reflex is suppressed in the conscious condition: effect of anesthesia.

To test the hypothesis that a muscle mechanosensitive reflex is suppressed in the conscious condition, we examined the effect of anesthesia on the cardiovascular responses to passive mechanical stretch of the hindlimb triceps surae muscle in six conscious cats. The triceps surae muscle was manually stretched for 30 s by extending the hip and knee joints and subsequently by dorsiflexing the ankle joint; the lateral gastrocnemius muscle was lengthened by 19 +/- 2.6 mm. Heart rate (HR) and mean arterial blood pressure (MAP) did not change significantly during passive stretch of the muscle in the conscious condition. At 10-40 min after intravenously administering pentobarbital sodium (20-25 mg/kg), the identical passive stretch of the triceps surae muscle was able to induce the cardiovascular responses; HR and MAP were increased by 14 +/- 1.3 beats/min and 14 +/- 1.4 mmHg, respectively, and the cardiovascular responses were sustained throughout the passive stretch. In contrast, stretching skin on the triceps surae muscle evoked no significant changes in HR and MAP in the anesthetized condition. When anesthesia became light 40-90 min after injection of pentobarbital and the animals started to show spontaneous body movement, the cardiovascular response to passive muscle stretch tended to be blunted again. It is therefore concluded that passive mechanical stretch of skeletal muscle is capable of evoking the reflex cardiovascular response, which is suppressed in the conscious condition but exaggerated by anesthesia.     

Effects of two different experimental situations of hypothyroidism on serum aldosterone concentration and plasma renin in rats

When hypothyroidism is induced surgically in early steps of development in the rat, an increase in serum aldosterone concentration (AC), in absence of changes in plasma renin activity (PRA), is observed. In contrast, in propylthiouracil (PTU) induced hypothyroidism, in adult animals, both AC and PRA decrease. Potassium iodide (KI) or triiodo-L-thyronine (T3) administration to thyroidectomized rats restores AC to normal levels, increasing PRA during the latter treatment. A close relationship between AC and plasma renin concentration (PRC) is observed in these experimental situations. The decrease in urinary aldosterone concentration (ACu), and the relation found between AC/ACu ratio and T3 concentration, suggest that metabolic clearance of aldosterone might be related to peripheric T3 levels in thyroidectomized animals, treated with KI or T3. These observations support the hypothesis, previously reported, which suggests different mechanisms involved in the control of aldosterone and renin release during the two different types of hypothyroidism.     

Lack of prostaglandin effect on sodium balance and hyperreninemia in adrenalectomized rats

Glucocorticoids are known inhibitors of prostaglandin production. Prostaglandin E2 (PGE2) and prostacyclin (PGI2) are promoters of natriuresis and renin release. Excessive prostaglandin production, therefore, might contribute to the altered sodium balance and renin release observed in primary adrenal insufficiency. To test this hypothesis, sodium balance and prostaglandin production were measured in adrenalectomized rats and in animals receiving prostaglandin inhibitors or replacement dexamethasone. Compared to sham-operated controls, adrenalectomized rats had decreased two-day sodium balance and elevated plasma renin concentration (PRC), renal PGE2 production, and renal 6-ketoprostaglandin F1α (6kPGF1α, the nonezymatic metabolite of PGI2); however, no appreciable change in aortic 6kPGF1α production was observed. Dexamethasone given to adrenalectomized rats normalized PRC but had no effect on sodium balance or prostaglandin production. Likewise, prostaglandin inhibitors did not alter the sodium balance or decrease the PRC post adrenalectomy.These data confirm renal prostaglandin production is increased in adrenalectomized rats, but suggest that the elevation is not due directly to glucocorticoid deficiency. Further, PRC levels in adrenal insufficiency do not appear to be prostaglandin mediated. In conclusion, excessive renal prostaglandin production does not contribute to altered sodium balance or increased PRC in adrenalectomized rats.     

Mechanism for the increase in plasma renin activity by pentobarbital anesthesia

The mechanism by which pentobarbital anesthesia causes increases in plasma renin activity (PRA) was examined in dogs infused with either propranolol or indomethacin, an inhibitor of prostaglandin synthetase. Infusion of propranolol at 1 mg/kg, (I.V.) followed by 0.6–0.7 mg/kg/hr decreased PRA from 6.98±2.49 ng/m1/hr during control periods to 1.58±0.79 ng/m1/hr 30 minutes after the injection of propranolol (P<0.025). Subsequent induction of anesthesia with sodium pentobarbital caused PRA to rise to 3.87±0.93 ng/m1/hr in 30 minutes. (P<0.01). Plasma potassium concentration decreased from 4.6±0.2 mEq/L to reach 4.0±0.1 mEq/L 30 minutes after induction of anesthesia (P<0.005). Infusion of indomethacin at 5 mg/kg, (I.V.) followed by 1.5 ? 3.1 mg/kg/hr into conscious dogs did not decrease PRA. In contrast to the report by Montgomery et al (Fed. Proc. 36: 989, 1977), we found that the increase in PRA after pentobarbital anesthesia could not be blocked by indomethacin. PRA was 5.3±1.2 ng/m1/hr(M ± SEM) during control periods and was 4.7±1.4 ng/m1/hr 30 minutes after the infusion of indomethacin (P<0.1). PRA increased to 10.9±2.3 ng/m1/hr, 9.2±2.2 ng/m1/hr, and 7.7±1.7 ng/m1/hr at 5, 15 and 30 minutes, respectively, after the administration of pentobarbital (P<0.005, P<0.025, P<0.05). PRA declined to 4.2±1.3 ng/m1/hr 60 minutes after pentobarbital anesthesia (P<0.1). It is concluded that the mechanism by which pentobarbital causes increases in PRA is independent of prostaglandins.