Biomedical subjects

C C Barney

Publications and source records attributed to C C Barney.

At least 37 records · Page 2Linked to original sources

PubMed1983

On the mechanism of serotonin-induced dipsogenesis in the rat.

Subcutaneous administration of l-5-hydroxytryptophan (5-HTP), the precursor of serotonin, to female rats induces copious drinking accompanied by activation of the renin-angiotensin system. Neither a reduction in blood pressure nor body temperature accompanied administration of 5-HTP. The objective of the present study was to determine whether serotonin-induced dipsogenesis, like that of 5-HTP, is mediated via the renin-angiotensin system. Serotonin (2 mg/kg, SC)-induced drinking was inhibited by the dopaminergic antagonist, haloperidol (150 micrograms/kg, IP), which also inhibits angiotensin II-induced drinking. Both captopril (35 mg/kg, IP), an angiotensin converting enzyme inhibitor, and propranolol (6 mg/kg, IP), a beta-adrenergic antagonist, blocked serotonin-induced dipsogenesis. The alpha 2-adrenergic agonist, clonidine (6.25 micrograms/kg, SC), which suppresses renin release from the kidney, attenuated serotonin-induced water intake. The dipsogenic responses to submaximal concentrations of both serotonin (1 mg/kg, SC) and isoproterenol (8 micrograms/kg, SC) were additive rather than interactive suggesting that similar pathways mediate both responses. The serotonergic receptor antagonist, methysergide (3 mg/kg, IP), inhibited serotonin-induced drinking but had no effect on isoproterenol (25 micrograms/kg, SC)-induced dipsogenesis. However, neither serotonin (2 mg/kg, SC) nor isoproterenol (25 micrograms/kg, SC)-induced drinking was inhibited by cinanserin (25 micrograms/kg, IP). These data indicate that serotonin induces drinking in rats via the renin-angiotensin system. However, the results of the studies using methysergide suggest that serotonin appears to act at a point prior to activation of beta-adrenoceptors in the pathway leading to release of renin from the kidneys.

Animals↗

PubMed1983

Effect of acute administration of isoproterenol and angiotensin II, separately and in combination, on water intake and blood pressure of rats.

The effects of administration of isoproterenol, a beta-adrenergic agonist, and angiotensin II, a peptide, separately and in combination, on water intake and blood pressure of rats were studied. The results of 6 factorially designed studies in which 4 different doses of each compound were administered revealed that water intakes increased directly with the logarithm of increasing doses of each. The effect of simultaneous administration of the 2 compounds on water intake was additive at submaximal doses of each. No interactive effects on water intake were observed when the 2 compounds were administered simultaneously in any study. Reduction in urine output appears to be a more sensitive response to administration of isoproterenol than increase in water intake since it was virtually abolished at a dose (2.5 micrograms/kg SC) that had no effect on water intake. The lowest doses of angiotensin II (25 and 50 micrograms/kg SC) had no significant effect on either water intake or urine output. The effect of simultaneous administration of both compounds on urine output was essentially the same as that accompanying administration of isoproterenol alone. Following administration of angiotensin II (150 micrograms/kg, SC) mean systemic blood pressure of unanesthetized, chronically cannulated rats reached maximal levels within 5 min and returned to pretreatment control level by 60 min. Following administration of isoproterenol (25 micrograms/kg, SC), mean systemic blood pressure decreased within 5 min, was maximally depressed by 30 min and had returned halfway to the pretreatment control level by 60 min. Simultaneous administration of isoproterenol and angiotensin II failed to induce a significant change in blood pressure. These results are of particular interest since they show that neither the pressor effect of angiotensin II nor the depressor effect of isoproterenol is essential for the induction of drinking by these 2 compounds.

Angiotensin II↗

PubMed1983

The effects of food deprivation on beta-adrenergic responsiveness in male rats.

Male rats were deprived of food for varying lengths of time (0-96 h) and their responses to beta-adrenergic stimulation with isoproterenol were tested. Food deprivation for 48 or 96 h attenuated the increase in tail skin temperature normally seen following administration of isoproterenol. The degree of attenuation was dependent on the duration of the deprivation period. Rats deprived of food for 96 h and then refed for 48, 96, or 144 h showed a return of tail skin temperature response to near normal levels. The increase in heart rate observed following administration of isoproterenol was also attenuated following 48 or 96 h of food deprivation. Again, the degree of attenuation was dependent on the duration of the deprivation period. Food deprivation for 96 h led to a decrease in basal plasma levels of T3, T4, and glucose. The increase in plasma glucose following administration of isoproterenol was also attenuated following 96 h of food deprivation. In contrast to the thermal, cardiac, and glucose responses, the dipsogenic response to isoproterenol was increased following food deprivation. The attenuation in beta-adrenergic responses observed in the food-deprived rats might help explain the effects of food deprivation on cold tolerance.

Animals↗

PubMed1983

Water deprivation-induced drinking in rats: role of angiotensin II.

The role of angiotensin II in the control of water intake following deprivation of water for varying lengths of time was studied. Male rats were deprived of water for 0, 12, 24, 36, or 48 h. Water intakes were measured with and without pretreatment with the angiotensin I-converting enzyme inhibitor, captopril (50 mg/kg, ip). Captopril had no significant effect on water intake following either 0 or 12 h of water deprivation. However, captopril significantly attenuated water intake following 24-48 h of water deprivation with the magnitude of the attenuation increasing as the length of the period of water deprivation increased. Plasma renin activity was significantly increased over control levels after 24-48 h of water deprivation but not after 12 h of water deprivation. Plasma renin activity tended to increase as the length of the water-deprivation period increased. Serum osmolality and sodium concentration were significantly increased over control levels following 12-48 h of water deprivation. Serum osmolality and sodium concentration failed to show any further increases with increasing length of water deprivation beyond the increases following 12 h of water deprivation. The data indicate that the water intake of water-deprived rats can be divided into an angiotensin II-dependent component and angiotensin II-independent component. The angiotensin II-independent component appears to be more important in the early stages of water deprivation whereas the angiotensin II-dependent component becomes more important as the length of the water-deprivation period increases.

Angiotensin II↗

PubMed1982

Promutagen activation in partially hepatectomized mice.

Mutagenic activity of aflatoxin B1 (AFB1) was followed in the Ames Salmonella/microsome test using liver S-9 from control and partially hepatectomized (PH) mice. The S-9 preparations from the PH mice were capable of inducing significantly greater AFB1 mutagenic activity to strain TA100 than S-9 preparations from either unoperated control, sham-operated control, or Aroclor 1254-induced mice. Increased activity was observed with S-9 preparations made at both 42 h and 148 h following PH.

Aflatoxin B1↗

PubMed1981

Peripheral conversion of L-5-hydroxytryptophan to serotonin induces drinking in rats.

Female rats administered serotonin (0.25 to 4.0 mg/kg, s.c.) showed a dose-dependent increase in water intake. The dipsogenic response was nearly maximal when 2 mg/lg was administered s.c. and plateaued by 2 hr after treatment. l-5-Hydroxytryptophan (5-HTP), the precursor of serotonin, is also a potent dipsogen which induces drinking by way of the renin-angiotensin system. The possibility that the dipsogenic activity of 5-HTP is dependent on decarboxylation to serotonin was the objective of these studies. Either benserazide (30 mg/kg. s.c.), a central and peripheral decarboxylase inhibitor, or carbidopa (6.5 mg/kg, s.c.), a peripheral decarboxylase inhibitor, was administered 15 min prior to the dipsogen. Both decarboxylase inhibitors attenuated the dipsogenic response to 5-HTP (25 mg/kg, s.c.) but not to serotonin (2 mg/kg, s.c.). The peripheral serotonergic receptor antagonist, methysergide (3 mg/kg, i.p.), blocked the dipsogenic responses to both 5-HTP (25 mg/kg, s.c.) and serotonin (2 mg/kg, s.c.). There was no interaction between 5-HTP (18 mg/kg, s.c.) and serotonin (1 mg/kg, s.c.) when administered simultaneously with respect to their dipsogenic effects. Thus, the drinking response accompanying administration of 5-HTP occurs following peripheral conversion to serotonin which, in turn, activates peripheral serotonergic receptors. The mechanisms(s) by which activation of peripheral serotonergic receptors increases water intake is not known, but appears to involve release of renin from the kidney.

5-Hydroxytryptophan↗

PubMed1981

Effects of serotonin and L-5-hydroxytryptophan on plasma renin activity in rats.

The effects of dipsogenic doses of l-5-hydroxytryptophan (5-HTP) and serotonin on plasma renin activity (PRA), blood pressure, and body temperature were determined in unanesthetized female rats. Both serotonin (2 mg/kg, s.c.) and 5-HTP (25 mg/kg, s.c.) induced six-fold increases in PRA measured 1 hr after drug administration. The central and peripheral decarboxylase inhibitor, benserazide (30 mg/kg, s.c.), as well as the peripheral decarboxylase inhibitor, carbidopa (6.5 mg/kg s.c.), prevented the increase in PRA associated with administration of 5-HTP. This suggests that 5-HTP must be converted to serotonin peripherally to increase PRA. At the doses used, serotonin decreased mean blood pressure and colonic temperature of unanesthetized rats while 5-HTP was without effect. The increase in PRA induced by 5-HTP does not appear, therefore, to be a response to either hypotension or a decrease in colonic temperature. Since 5-HTP must be converted to serotonin to initiate both a drinking response and an increase in PRA, the results suggest that the decrease in blood pressure and colonic temperature following administration of serotonin may not be important in induction of the drinking response and the increase in PRA. The mechanism by which activation of the renin-angiotensin system occurs following peripheral administration of either 5-HTP or serotonin remains for further study.

5-Hydroxytryptophan↗

PubMed1981

Thermoregulatory responses of tailed and tailless rats to isoproterenol.

Colonic temperatures were measured in tailed and tailless rats at an ambient temperature (Ta) of 26 degrees C prior to and following administration of isoproterenol, a beta-adrenergic agonist, at doses of 0, 12.5, 25.0, 50.0, and 100.0 micrograms.kg-1. There was no significant difference between the colonic temperatures of tailed and tailless rats before drug injection. However, mean colonic temperature of tailless rats increased to a maximal level approximately 0.3 degrees higher than that of tailed rats after injection of 25.0, 50.0, and 100.0 micrograms isoproterenol per kilogram. The duration of the hyperthermic response was 50-60 min longer in tailless than tailed rats after administration of 50 and 100 micrograms isoproterenol per kilogram. The rate of oxygen consumption (heat production) increased by 4.5 mL.min-1.kg-0.75 in both tailed and tailless rats after administration of 50 micrograms isoproterenol per kilogram, the only dose tested. Mean colonic temperature of tailless rats was significantly higher, by 0.2-0.5 degrees than that of tailed rats during the initial 60 min of exposure to Ta 36 degrees C and during the first 40 min following removal from Ta 40 degrees C to Ta 28 degrees C. These results suggest that the tail of the rat is required for short-term maintenance of colonic temperature during both external and internal heat stresses.

Animals↗

PubMed1981

Metabolic responsiveness of spontaneously hypertensive rat to isoproterenol.

The metabolic responsiveness of spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) normotensive rats to administration of the beta-adrenergic agonist, isoproterenol, was assessed by changes in tail-skin temperature, heart rate, and plasma glucose concentration after administration of graded doses of isoproterenol. The increases in mean tail-skin temperature accompanying administration of isoproterenol at doses of 5, 10, and 40 micrograms/kg sc were significantly (P less than 0.05) greater for SH than for WKY rats. Resting colonic temperatures of the SH rats were also significantly (P less than 0.01) higher than those of the WKY normotensive rats. Mean maximal heart rates of unanesthetized SH rats after administration of isoproterenol at doses of 5, 10, and 20 micrograms/kg sc increased to levels significantly (P less than 0.05-0.01) higher than those of WKY normotensive rats. Resting heart rates were similar in both groups. Increases in plasma glucose concentration after administration of isoproterenol at doses of 5, 10, and 20 micrograms/kg sc were significantly (P less than 0.05) greater in the SH rats compared with the WKY rats. These results suggest that the SH rat has a significantly greater metabolic responsiveness to beta-adrenergic stimulation, as assessed by three separate tests of beta-adrenergic function, than does the WKY rat.

Animals↗

PubMed1981

Prostaglandins and temperature regulation in the rhesus monkey.

The role of prostaglandins in nonfebrile temperature regulation in the rhesus monkey (Macaca mulatta) was investigated, Indomethacin, a potent inhibitor of prostaglandin synthesis, produced only a slight (less than 0.8 degrees C) fall in core temperature when administered intravenously (2-4 mg/kg) to warm-, cold-, and nonacclimated afebrile rhesus monkeys at ambient temperatures of 18, 27, and 33 degrees C. The fall in the core temperature was independent of the state of temperature acclimation and was brought about by nonregulated means. In addition, cold acclimation in the rhesus monkey was not associated with any change in hypothalamic sensitivity to the hyperthermic effects of exogenous prostaglandin E1. The results indicate that hypothalamic prostaglandins are not involved in normal temperature regulation of the monkey or in the process of temperature acclimation.

Adaptation, Physiological↗

PubMed1981

Proposed mechanism for increased thyroxine deiodination in cold-acclimated rats.

Groups of male rats were administered isoproterenol (ISO), thyroxine (T4), or both (ISO + T4) daily for 20 days in an attempt to mimic the effect of cold acclimation on the rate of outer-ring deiodination of T4 to triiodothyronine (T3) by 2,000-g supernatants of homogenates of liver and kidney. The rates of hepatic and renal deiodination of T4 to T3 in an additional group of rats exposed to 4 +/- 1 degree C for 20 days were 53 and 71% higher, respectively, than control. Administration of ISO (100 micrograms . kg-1 . day-1) did not affect the rate of deiodination of T4 to T3 by either hepatic or renal tissue. Administration of T4 (50 micrograms . kg-1 . day-1) resulted in rates of hepatic and renal deiodination of T4 that were 297 and 222% higher, respectively, than control. Administration of ISO + T4 resulted in a rate of conversion of T4 to T3 not significantly different from that observed when T4 was administered alone. Serum concentration of T4 was elevated after administration of both T4 and ISO + T4, whereas serum concentration of T3 was elevated significantly above that of control only in the cold-acclimated group. These results suggest that the increased rate of 5'-monodeiodination of T4 by hepatic and renal homogenates from cold-acclimated rats is not a result of increased beta-adrenergic activity but can be accounted for by the increase in thyroid activity observed in these animals.

Acclimatization↗

PubMed1981

Dipsogenesis in cold-acclimated rats.

Water intakes of control rats kept at 25 degrees C and cold-acclimated rats kept at 6 degrees C for at least 4 weeks were compared when both groups were at 25 degrees C. Cold-acclimated rats exhibited an increase in water intake (thermogenic drink) during the first but not the second hour after removal from the cold. Cold-acclimated rats, administered the dipsogenic agents angiotensin I, angiotensin II, isoproterenol or serotonin, had water intakes not significantly different from control rats. Administration (1% of body weight) of several different doses of hypertonic NaCl (0.25 to 1.00M) intraperitoneally increased water intake to the same level in both control and cold-acclimated rats. Water deprivation for 24 h, initiated either 2 or 24 h after removal of cold-acclimated rats from the cold, resulted in water intakes not significantly different between cold-acclimated and control rats. In spite of an initial thermogenic drink on removal of cold-acclimated rats from cold, cold-acclimation does not appear to alter the dipsogenic responsiveness of rats to either extracellular or intracellular dipsogenic stimuli, or to a dipsogenic stimulus (dehydration) involving both.

Acclimatization↗

PubMed1980

beta-adrenergic responsiveness of rats treated chronically with isoproterenol.

The effect of chronic administration of isoproterenol on isoproterenol-induced thirst and isoproterenol-induced changes in heart rate and selected organ weights of male rats was studied. Administration of 25 micrograms isoproterenol/kg, s.c., in saline daily for 10 days was accompanied by a significant attenuation of the characteristic increase in water intake following a challenging dose of isoproterenol (25 micrograms/kg, s.c.) on the 11th day. Administration of 25 micrograms isoproterenol/kg, s.c., every 2nd, 3rd or 4th day for 10 days was without significant effect on water intake following isoproterenol (25 micrograms/kg, s.c.) on the 11th day. Administration of 25 micrograms isoproterenol/kg, s.c., every day for 10 days led to a slight increase in cardiac responsiveness to a challenging dose of isoproterenol (25 micrograms/kg) on the 11th day. Chronic treatment with this low dose of isoproterenol for 10 days was also accompanied by a significant increase in the ratio of heart weight to body weight but no significant changes in the ratio of kidney, adrenal, thyroid, spleen, or interscapular brown fat to body weight. Thus, daily administration of the beta-adrenergic agonist isoproterenol for 10 days can alter beta-adrenergic responsiveness in the rat with beta 1 (heart rate) and beta 2 (thirst) mediated responses showing opposite effects. In addition, the results suggest that tests of beta-adrenergic responsiveness must be assessed in terms of the frequency of administration of the agonist.

Animals↗

PubMed1980

Changes in beta-adrenergic responsiveness of rats during chronic cold exposure.

Administration of isoproterenol (50 micrograms/kg sc) to rats that had been exposed to cold (6 degrees C) for 10, 15, and 25 days was accompanied by a greater increase in tail skin and colonic temperatures than in controls kept at 25 degrees C. Administration of isoproterenol (8 micrograms/kg sc) to cold-treated rats (1, 3, 5, 7, 14, and 28 days) increased heart rates above that of controls. However, resting unstimulated heart rates of cold-treated rats were also increased above that of controls after 1, 3, 5, and 7 days of cold exposure but were not different from controls after 14 and 28 days. Cold exposure also led to time-dependent increases in the weights of heart, adrenals, and interscapular brown fat. Thus, chronic exposure of rats to cold is accompanied by an increase in responsiveness of both heart rate and tail skin and colonic temperatures to beta-adrenergic stimulation. The results also suggest that increases in responsiveness to a beta-adrenergic agonist may not occur at the same time for the different beta-adrenergic-mediated metabolic and cardiovascular responses in cold-treated rats.

Acclimatization↗

PubMed1980

The effect of acute administration of an angiotensin converting enzyme inhibitor, captopril (SQ 14,225), on experimentally induced thirsts in rats.

In order to assess the role of angiotensin in the genesis of certain types of thirst, rats were administered the angiotensin converting enzyme inhibitor, captopril, in an attempt to block the increased water intake induced either by water deprivation or by i.p. administration of hypertonic saline. Water deprivation for 24 hr resulted in an increased water intake. Acute administration of 50 mg of captopril per kg i.p. at 45 or 60, but not at 15 or 30, min before return of water to the dehydrated rats significantly attenuated the drinking response. Rats administered 1% b.wt. i.p. of 0.25, 0.50, 0.75 or 1.00 M NaCl solution increased proportionately their water intake. Acute administration of 35 mg of captopril per kg b. wt. i.p. 15 min before loading with NaCl solution at any of the above concentrations had no effect on the increased thirst induced. These findings suggest that hypertonic saline-induced thirst is not mediated by angiotensin II receptors while water deprivation-induced thirst may involve both osmoreceptors and angiotensin II receptors.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1979

Effect of an angiotensin converting enzyme inhibitor (SQ 14,225) on beta-adrenergic and angiotensin-induced thirsts.

The effect of acute administration of SQ 14,225, a new angiotensin converting enzyme inhibitor, on the drinking response of female rats administered either isoprenaline, angiotensin I, or angiotensin II was studied during 2 h after treatment. Administration of isoprenaline (25 micrograms/kg body wt) was accompanied by a significant increase in water intake when compared with saline-treated controls. Acute administration of a constant dose of isoprenaline (25 micrograms/kg body wt) and increasing doses of SQ 14,225 (5--50 mg/kg) was accompanied by a dose-related, linear decrease in water intake. Acute administration of either angiotensin I or angiotensin II (200 micrograms/kg body wt) was accompanied by a significant increase in water intake. The dipsogenic response to angiotensin II was not affected by acute administration of 35 mg SQ 14,225/kg body wt. However, at the same dose of SQ 14,225, angiotensin I-induced thirst was attenuated. Since isoprenaline-induced and angiotensin I-induced, but not angiotensin II-induced, thirsts are blocked by SQ 14,225, the results suggest that isoprenaline-induced thirst is mediated by way of the renin--angiotensin system.

Angiotensin I↗

PubMed1979

The effect of ambient temperature on beta-adrenergic responsiveness in rats.

The responses of tail skin and colonic temperatures of female rats to ambient temperatures of 20, 22, 24, 26, 28, and 30 degrees C were measured. Within this range, colonic temperature was stable while tail skin temperature increased linearly with increasing ambient temperature. Administration of the beta-adrenergic agonist, d,l-isoproterenol, at 10.0, 25.0, and 62.5 micrograms/kg, sc, at each ambient temperature was accompanied by increases in tail skin and colonic temperatures that were dependent on both the dose of isoproterenol administered and the ambient temperature. The integrated responses of tail skin temperature following administration of the three doses of isoproterenol were maximal at an ambient temperature of 26 degrees C while the integrated responses of colonic temperature were maximal at 30 degrees C. The results suggest that tests of beta-adrenergic responsiveness using this technique should be performed at an ambient temperature of 26 degrees C for maximal sensitivity.

Animals↗

PubMed1979

Effect of chronic treatment with desoxycorticosterone on the dipsogenic response of rats to isoproterenol and angiotensin.

Administration of desoxycorticosterone (DOC) at a dose of 0.5 mg/kg/day to male rats for 6 weeks attenuated significantly the drinking response to acute subcutaneous administration of 5, 10 and 20 microgram isoproterenol/kg body weight. Chronic administration of DOC did not prevent the drinking response to acute intraperitoneal administration of angiotensin II (200 microgram/kg body weight). In contrast, the drinking response was enhanced compared with that of control rats given angiotensin II acutely. While attenuation of the drinking response to isoproterenol in DOC-treated rats may be attributed to depletion of renin from their kidneys, the mechanisms responsible for the enhanced drinking response to angiotensin II are not clearly understood.

Angiotensin II↗