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The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial.

OBJECTIVE: Benzodiazepines are the mainstay of treatment for mild-to-moderate alcohol withdrawal in outpatient settings, but they can interact with alcohol, cause motor incoordination, or be abused. This study compared the therapeutic responses of the benzodiazepine lorazepam and the anticonvulsant carbamazepine for the outpatient treatment of acute alcohol withdrawal in terms of patients' previous detoxification histories, and compared the effects of these 2 medications on drinking behaviors in the immediate postdetoxification period. DESIGN: This was a randomized double-blind trial comparing patient responses to carbamazepine and lorazepam across 2 levels of detoxification histories (0-1 or >or=2 previous medicated detoxifications). SETTING: A university medical center substance abuse clinic in Charleston, SC. PATIENTS: One hundred thirty-six patients in moderate alcohol withdrawal were randomized. Major exclusions were significant hepatic or hematologic abnormalities and use of medications that could alter withdrawal symptoms. INTERVENTIONS: Patients received 600-800 mg of carbamazepine or 6-8 mg of lorazepam in divided doses on day 1 tapering to 200 mg of carbamazepine or 2 mg of lorazepam. MAIN OUTCOME MEASURES: The Clinical Institute Withdrawal Assessment for Alcohol-Revised was used to assess alcohol withdrawal symptoms on days 1 through 5 and postmedication at days 7 and 12. Daily drinking was measured by patient report using a daily drinking log and a breath alcohol level with each visit. Side effects were recorded daily. RESULTS: Carbamazepine and lorazepam were equally effective at decreasing the symptoms of alcohol withdrawal. In the post-treatment period, 89 patients drank on at least 1 day; on average, carbamazepine patients drank less than 1 drink per drinking day and lorazepam patients drank almost 3 drinks per drinking day (P =.003). Among those with multiple past detoxifications, the carbamazepine group drank less than 1 drink per day on average and the lorazepam group drank about 5 drinks per day on average (P =.033). Lorazepam-treated patients had a significant rebound of alcohol withdrawal symptoms post-treatment (P =.007) and the risk of having a first drink was 3 times greater (P =.04) than for carbamazepine-treated patients. Twenty percent of lorazepam-treated patients had dizziness, motor incoordination, or ataxia and did not recognize their impairment. Twenty percent of carbamazepine-treated patients reported pruritus but no rash. CONCLUSIONS: Carbamazepine and lorazepam were both effective in decreasing the symptoms of alcohol withdrawal in relatively healthy, middle-aged outpatients. Carbamazepine, however, was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, especially for those with a history of multiple treated withdrawals.

Adult↗

Are there differences between older persons who screen positive on the CAGE questionnaire and the Short Michigan Alcoholism Screening Test-Geriatric Version?

OBJECTIVES: To determine (1) the extent of agreement between the CAGE (acronym for cut down, annoyed by criticism, guilty about drinking, eye-opener drinks) and the Short Michigan Alcoholism Screening Test-Geriatric Version (SMAST-G) in identifying older persons who may have possible alcohol use disorders (AUDs) and (2) whether persons identified as having possible AUDs by each of these screening measures differ in their drinking, demographic, or health-related characteristics. DESIGN: Secondary analysis of a cross-sectional study using data from a self-administered mailed survey sample. SETTING: Three organizations were surveyed: (1) members of the American Association of Retired Persons and, in southern California, (2) managed care enrollees in a large medical group and (3) attendees of a community-based senior health center. PARTICIPANTS: One thousand eight hundred eighty-nine persons aged 55 and older completing a health risk appraisal for older persons (Health Risk Appraisal for the Elderly (HRA-E)). MEASUREMENTS: The HRA-E included items on drinking behaviors (including amount of alcohol use, the CAGE, and the SMAST-G) and health and demographic characteristics. RESULTS: Twenty-six percent of all persons screened positive on the CAGE or the SMAST-G. Fewer than half of all persons screening positive on either the CAGE or the SMAST-G, screened positive on both measures. Among current drinkers, persons screening positive on the SMAST-G alone drank less than persons screening positive on the CAGE alone, and these persons drank less than those screening positive on both the SMAST-G and the CAGE. More men screened positive on the CAGE alone than on the SMAST-G alone. CONCLUSION: Fewer than half of persons screening positive on either the CAGE or the SMAST-G screened positive on both measures, suggesting that these instruments may be capturing different aspects of unsafe drinking. A screening strategy employing both brief measures may identify more AUDs among older persons having differing demographic and health characteristics.

Age Factors↗

The relationship of alcohol use to cocaine relapse in cocaine dependent patients in an aftercare study.

OBJECTIVE: To examine the relationship between alcohol use and cocaine relapse. METHOD: Ninety-eight cocaine-dependent male patients in aftercare were followed for 6 months following completion of an intensive outpatient rehabilitation program (IOP). Past and current alcohol dependence was assessed at entrance into aftercare, and drinking behavior prior to cocaine relapse and "near miss" episodes was assessed at 3- and 6-month follow-ups. Data on cocaine and alcohol use throughout the follow-up were also obtained. RESULTS: Patients who had never met criteria for alcohol dependence and those with current alcohol dependence had worse cocaine outcomes (cocaine use on 10% and 7% of the days in the follow-up, respectively) than those with past alcohol dependence (cocaine use on 3% of the days in the follow-up), although alcohol dependence status no longer predicted cocaine use outcomes when cocaine use in IOP was controlled. Alcohol use in 4 of the first 5 follow-up months significantly predicted cocaine relapse status in the next month after cocaine use in IOP and alcohol dependence diagnosis at baseline were controlled. Patients who experienced cocaine relapses were much more likely to report drinking before the onset of the episode than those who had "near misses," particularly on the day of the episode (40% vs. 6% at 3 months; 62% vs. 0% at 6 months). Alcohol did not appear to be a factor in the relapses of cocaine patients with no history of alcohol dependence, even though they did report drinking on 5% of the days in the follow-up. CONCLUSIONS: Relapse prevention efforts with cocaine abusers who have histories of alcohol dependence should include interventions designed to reduce drinking.

Adult↗

Effects of voluntary ethanol intake on the expression of Ca(2+) /calmodulin-dependent protein kinase IV and on CREB expression and phosphorylation in the rat nucleus accumbens.

To define the molecular basis of alcohol drinking behaviors, the effects of voluntary ethanol intake on the expression of Ca(2+)/calmodulin-dependent protein kinase IV (CaM kinase IV) and on the expression and phosphorylation of cAMP responsive element binding protein (CREB) [corrected] in the nucleus accumbens (NAc), central amygdala, and frontal cortex of rats were investigated. Voluntary ethanol intake significantly decreased the expression of CaM kinase IV and CREB phosphorylation but not of CREB protein levels [corrected], specifically in the shell of NAc. These changes were not observed in the core of NAc, central amygdala and frontal cortex. Mianserin treatment significantly attenuated ethanol intake and antagonized the voluntary ethanol-induced reduction in expression of CaM kinase IV and CREB phosphorylation in the shell of NAc. This is the first evidence to suggest that decreased CaM kinase IV-dependent CREB phosphorylation in the shell region of NAc may play a role in the reward mechanisms of alcohol drinking.

Alcohol Drinking↗

Mouthwash in the etiology of oral cancer in Puerto Rico.

OBJECTIVES: To determine if the risk of cancers of the mouth and pharynx is associated with mouthwash use in Puerto Rico, an area of relatively high risk. METHODS: Interviews were conducted with 342 cases of oral and pharyngeal cancer registered in Puerto Rico and diagnosed between 1992 and 1995 and with 521 population-based controls regarding mouthwash use and other factors. Mouthwash-related risks were estimated using unconditional logistic regression controlling for potential confounders. RESULTS: The adjusted odds ratio associated with using mouthwash with an alcohol content of 25% or greater was 1.0. Risks were not higher with greater frequency, years of use, or lifetime mouthwash exposure. Among tobacco and alcohol abstainers the odds ratio associated with mouthwash use was 2.8 (CI = 0.8-9.9), in contrast to 0.8 (CI = 0.4-1.7) and 0.9 (CI = 0.6-1.3) among those with light and heavy cigarette smoking/alcohol drinking behaviors, respectively. CONCLUSIONS: There was no overall increased risk of oral cancer associated with mouthwash use. An elevated, but not statistically significant, risk was observed among the small number of subjects who neither smoked cigarettes nor drank alcohol, among whom an effect of alcohol-containing mouthwash would be most likely evident. Our findings indicate the need to clarify the mechanisms of oral carcinogenesis, including the possible role of alcohol-containing mouthwash.

Adult↗

Family history of alcoholism and childhood adversity: joint effects on alcohol consumption and dependence.

Empirical studies provide substantial evidence that having a family history of alcoholism increases the risk of developing alcohol dependence; however, some of this effect may be caused by nonspecific childhood socioeconomic adversity common in families with an alcohol-dependent parent. In this study, we examine joint effects of family history and childhood adversity within a sample of 509 men and 217 women over age 40. The measures analyzed were included in routine screening assessments for participants in various studies at the University of Michigan Alcohol Research Center. About 60% of the men and 45% of the women were alcohol-dependent. About 30% reported an alcoholic parent. Degree of family history affected drinking behavior for both men and women. There were also environmental effects on the same measures for both men and women. Childhood socioeconomic adversity was reported more frequently by participants with an alcoholic parent, but adversity effects were also shown for those with a negative family history. The risk of alcohol dependence was additively increased by a positive family history and childhood socioeconomic adversity. The environmental effects identified in this study are promising evidence for nonspecific factors that moderate family history risk for development of alcohol problems.

Adult↗

Are educational aspirations associated with the risk of alcohol use and alcohol use-related problems among adolescents?

OBJECTIVE: Using prospective data, we hypothesized that public middle school students with high educational aspirations would report less alcohol use, and alcohol use-related problems in the subsequent year. METHODS: The participants for these analyses included students, ages 11 to 14 years old, participating in a longitudinal study in an urban sample of public schools (n = 1229). As part of the prospective annual assessments of the students, in 1992 (to) and 1993 (t1), data on educational aspirations and on alcohol use, and alcohol use-related problems were gathered. Latent variable modeling was used to assess the relationship between educational aspirations at baseline (to) and subsequent year drinking behavior (t1) in two separate models, one to examine the relationship of educational aspirations with self-reported alcohol use (model 1), and another to examine the association with alcohol use-related problems (model 2). Potential confounding by age, sex, race-ethnicity, alcohol use by peers, self-reported school performance, and neighborhood environment was held constant in each model. In addition, each model took into account the prior year report of alcohol use and alcohol use-related problems, respectively. RESULTS: The evidence indicated that students with high aspirations were no more nor less likely to report subsequent alcohol use [beta = 0.15, 95% confidence interval (CI) = -0.19, 0.49; p = 0.38] nor alcohol use-related problems (beta = -0.009, CI = -0.07, 0.06; p = 0.80). Other characteristics were associated with alcohol use at follow-up and included race-ethnicity (being non-Black), neighborhood environment, and having friends who drink alcohol. Characteristics associated with alcohol use-related problems at the time of the follow-up interview also included race-ethnicity, peer drinking, neighborhood environment, as well as older age. CONCLUSIONS: Findings from the current study do not support the hypothesis that educational aspirations have significant influences on alcohol consumption or drinking problems in this study population of urban, predominantly Black students. As such, this work helps to advance our understanding of suspected relationships between educational aspirations, as well as factors associated with resilience to alcohol use and the occurrence of alcohol use-related problems.

Achievement↗

Pharmacogenomics of alcohol response and addiction.

Alcoholism is a complex psychiatric disorder that has high heritability (50-60%) and is relatively common; in the US the lifetime prevalence of alcohol dependence is 20% in men and 8% in women. Current psychosocial and pharmacological therapies have relatively modest effects. Treatment is complicated by the fact that alcoholism is often co-morbid with other disorders, including anxiety, depression, and antisocial personality disorder. Approximately 80% of alcoholics smoke cigarettes and there is considerable genetic overlap between nicotine and alcohol addiction. Convergent evidence supports the classification of alcoholics into two broad categories: type 1 - later onset with feelings of anxiety, guilt, and high harm avoidance; and type 2 - early age of onset, usually men, impulsive, antisocial, and with low levels of brain serotonin. The pharmacogenomics of alcohol response is well established; genetic variants for the principal enzymes of alcohol metabolism influence drinking behavior and protect against alcoholism. Vulnerability to alcoholism is likely to be due to multiple interacting genetic loci of small to modest effects. First-line therapeutic targets for alcoholism are neurotransmitter pathway genes implicated in alcohol use. Of particular interest are the 'reward pathway' (serotonin, dopamine, GABA, glutamate, and beta endorphin) and the behavioral stress response system (corticotrophin-releasing factor and neuropeptide Y). Common functional polymorphisms in these genes are likely to be predictive (although each with small effect) of individualized pharmacological responses. Genetic studies, including case-control association studies and genome wide linkage studies, have identified associations between alcoholism and common functional polymorphisms in several candidate genes. Meanwhile, the current pharmacological therapies for alcoholism are effective in some alcoholics but not all. Some progress has been made in elucidating the pharmacogenomic responses to these drugs, particularly in the context of the type 1/type 2 classification system for alcoholics.

Alcohol Drinking↗

[Criminal responsibility in drunkenness].

Surveying government policies and programmes related to drinking problems and the means of controlling drinking behavior apart from criminal law, the author reaches the conclusion that significant resources are needed for the implementation of these policies. Regarding the state of unconscious drunkenness, the author is of the opinion that there are no serious reasons to justify holding a person criminally responsible for an action committed in a "non compos" state due to drunkenness. However, if a person becomes drunk through his own fault, he creates a situation of serious risk, which justifies holding the person responsible. The author believes that the 1948 state of affairs should have been adapted to the requirements of crime policy.

Alcohol Drinking↗

Drunk driving and the alcoholic offender: a new approach to an old problem.

Health laws in every state recognize alcoholism as a treatable disease. State drunk driving laws, however, inadequately provide for alcoholic drunk drivers. Studies show that problem drinkers make up as much as two-thirds of the DWI offender class. Alcoholic drunk drivers cannot fully conform their drinking behavior to the dictates of the law as long as their alcoholism remains untreated. This Note argues that the law should consistently treat alcoholism as a disease. This Note suggests that the most appropriate way for the legal system to deal with alcoholic DWI offenders is to suspend the offender's license until he can show that he has successfully completed an initial alcohol detoxification/rehabilitation program. In addition, because alcoholism requires lifelong treatment, alcoholic drivers should be required to present periodic documentation that their condition is under supervised treatment. Epileptic drivers are handled in a similar manner in most states.

Alcohol Drinking↗

Community prevention of alcohol problems.

Local communities have begun using policy to affect the drinking environment itself as an approach to reducing alcohol involved trauma. That is, policy is used to produce structural changes in the drinking environment. In turn, changes in the environment effect changes in drinking behavior. This paper describes an effort in three communities in two states to reduce alcohol problems at the community level, "Preventing Alcohol Trauma: A Community Trial." This trial was a 5-year research project with a goal to reduce local alcohol-involved injuries and deaths in three experimental communities with populations of approximately 100,000 each (one in northern California, one in southern California, and one in South Carolina). The communities contained racial and ethnic diversity as well as a mix of urban, suburban, and rural settings. Each of these three communities had a control community that did not receive the prevention interventions. The project used an environmental policy approach to prevention and five mutually reinforcing components were implemented: (1) community mobilization to develop community organization and support, (2) responsible beverage service to establish standards for servers and owners/managers of on-premise alcohol outlets to reduce their risk of having intoxicated and/or underage customers in bars and restaurants. (3) a drinking and driving component to increase local drunk-driving enforcement efficiency and to increase the actual and perceived risk that drinking drivers would be detected, (4) an underage drinking component to reduce retail availability of alcohol to minors, and (5) an alcohol access component to use local zoning powers and other municipal controls of outlet numbers and density to reduce availability of alcohol. Results show that the project reduced alcohol-involved crashes, lowered sales to minors, increased the responsible alcohol serving practices of bars and restaurants, and increased community support and awareness of alcohol problems.

Accidents, Traffic↗

The effects of naltrexone on alcohol and cocaine use in dually addicted patients.

Concurrent dependence on cocaine and alcohol is common among patients seeking addiction treatment. This study was undertaken to explore the effectiveness of naltrexone (150 mg) as a potential treatment for patients who are alcohol and cocaine dependent. Of 15 subjects enrolled in the 12-week, open medication trial, 7 subjects did not complete the study. Relapse to clinically significant drinking occurred in 7 subjects (47%). There was a reduction in the average daily amount of alcohol consumed from pretreatment to treatment (p < .001) and the percentage of days engaged in drinking behavior (p < .001). Similarly, there was a reduction in the average weekly amount spent on cocaine from pretreatment to treatment (p = .001) and the percentage of days using cocaine (p < .001). This preliminary study suggests that naltrexone (150 mg) may be tolerable in patients dependent upon alcohol and cocaine and may be effective in reducing both cocaine and alcohol use. The results of this study provide a rationale for a double-blind placebo-controlled study of the efficacy of naltrexone in this difficult to treat but prevalent population.

Adult↗

Interest in a stepped approach model (SAM): identification of recruitment strategies for university alcohol programs.

This study evaluates interest in a stepped approach model (SAM) of service delivery and identifies variables to enhance recruitment to alcohol programs. Subjects were 2,443 college student drinkers (1,420 men and 1,023 women) at a large midwestern university (selected by stratified systematic sampling) who completed a questionnaire on drinking behavior and interest in five intervention steps. Results indicated that there was more interest in interventions that required less time, which supports predictions of SAM. Overall lack of interest peaked at 67% for men and 65% for women and did not change significantly across the last three steps of SAM, which included traditional interventions of group and individual counseling. The data suggest that the stepped approach is more viable than conventional approaches, recruitment is unquestionably an exigent research priority because of the overwhelming lack of interest in alcohol programs, and specific variables that were identified may be important for recruiting particular subgroups.

Adolescent↗

An immunotoxin, anti-VIP antibody-ricin A chain conjugate eliminates neurons in the hypothalamic suprachiasmatic nucleus selectively and abolishes the circadian rhythm of water intake.

In mammals, a master circadian oscillator is known to be located in the suprachiasmatic nucleus (SCN) of the hypothalamus. We examined the function of SCN neurons involved in the mechanism of circadian rhythm of water intake by lesioning them with an immunotoxin, anti-vasoactive intestinal polypeptide (VIP) antibody-ricin A conjugate. We found that the immunotoxin had a specific lethal effect on cultured PC12h cells when VIP was added to the medium. When the conjugate was infused into the third cerebral ventricle of rats above the SCN, two specific types of selective lesions of neurons were observed in the SCN: selective lesions of neurons containing arginine vasopressin (AVP) (AVP-neurons), and selective lesions of neurons containing VIP (VIP neurons). The former lesions caused disappearance of the circadian rhythm of drinking behavior, whereas the latter lesions did not affect the rhythm of water intake under constant dim lighting. Lesions that did not selectively affect one of these neurochemically identified SCN cell populations were also observed after the infusion of the conjugate or normal rabbit serum immunoglobulin G-ricin A chain conjugate. If these nonspecific lesions included entire region of the SCN, the circadian rhythm of water intake was abolished. These findings suggest that SCN neurons bearing VIP receptors such as AVP neurons, but not VIP neurons, may be involved in the mechanism of the circadian rhythm of water intake.

Animals↗

Water metabolism of dairy cattle.

Lactating dairy cows metabolize large amounts of water and are affected rapidly by water deprivation. Total body water, half-life of body water, size of component pools, and exchanges among them have been quantitated in several studies. The data underscore the dynamic nature of water metabolism in lactating cows. Water is lost in milk, urine, feces, and various forms of evaporation. Sources of water include drinking, feed, and metabolic (oxidation) water. Factors that have been shown to influence drinking behavior include eating pattern, water temperature, whether water is given in a trough or water bowl, flow rates into water bowls, animal dominance if water bowls are shared, and stray voltage. Important environmental factors modulating water consumption of dairy cattle are DMI, nature of the diet, milk production, temperature, and humidity. Equations have been proposed to predict water consumption based on measures of some of these variables. Water is of paramount importance both physiologically and nutritionally; therefore, it is not surprising that its metabolism indirectly may affect many feeding and management decisions. Ample water of acceptable quality must be provided to maximize milk production.

Animal Feed↗

Alcohol-naïve alcohol-preferring (P) rats exhibit higher local cerebral glucose utilization than alcohol-nonpreferring (NP) and Wistar rats.

BACKGROUND: The present study determined local cerebral glucose utilization (LCGU) rates in alcohol-naïve alcohol-preferring (P), alcohol nonpreferring (NP), and outbred Wistar rats to test the hypothesis that innate differences in functional neuronal activity are present in limbic regions as a result of selective breeding for high-alcohol drinking behavior. METHODS: All procedures were conducted during the dark cycle. 2-[14C]deoxyglucose ([14C]2-DG; 125 microCi/kg) was injected intravenously and timed arterial blood samples were collected during the following 45 min and assayed for glucose and [14C]2-DG content. Rats were then decapitated, the brains removed and frozen to -70 degrees C, and 20 microm coronal sections were prepared for quantitative autoradiographic analysis. RESULTS: Rates of LCGU were determined in 55 regions and subregions, including limbic, cortical, and subcortical structures. LCGU rates were significantly (p < 0.01) higher in several limbic (e.g., ventral tegmental area, nucleus accumbens shell, olfactory tubercle, medial prefrontal cortex, and lateral hypothalamus), cortical (e.g., parietal, temporal, occipital, cingulate, piriform, and entorhinal), and subcortical (e.g., thalamus, habenula, preoptic area, and striatum) regions in P rats, compared with NP and Wistar rats, whereas rates in Wistar rats were higher in a few regions (e.g., CA1 and CA3 regions of the posterior hippocampus) than NP rats. CONCLUSIONS: The data suggest that selective breeding for high-alcohol drinking produces intrinsically higher functional neuronal activity in the central nervous system regions of the high-alcohol consuming P line compared with low-alcohol drinking NP or Wistar rats, although these differences may not generalize to other rat lines selectively bred for divergent alcohol drinking.

Alcoholism↗

Dose effects of human renin in rats transgenic for human angiotensinogen.

We examined the effect of chronic human renin infusion and human renin inhibition on blood pressure in a unique transgenic rat model. We infused incremental doses of human renin (1 to 500 ng/h) with minipumps for 10 days into rats harboring the human angiotensinogen gene [TGR (hAOGEN)1623]. We measured blood pressure and heart rate continuously by telemetry. We found that human renin at 5 ng/h was necessary to increase blood pressure, whereas 10 ng/h caused systolic blood pressure to increase to 215 +/- 13 mm Hg. Heart rate decreased initially but then increased by 100 beats per minute compared with basal values. Drinking behavior also increased. Doses as high as 500 ng/h did not increase blood pressure further. A linear relationship was found between the log of plasma renin activity and systolic blood pressure that increased in slope from days 2 to 9. Rat angiotensinogen levels were low and not influenced by human renin infusion. Human angiotensinogen levels remained stable until 500 ng/h human renin was infused, at which time they decreased by 50% at 9 days. Rat renin gene expression (RNase protection assay) was decreased by human renin infusion, whereas rat and human angiotensinogen gene expressions in liver and kidney as well as angiotensin-converting enzyme gene expression in kidney were not affected. The human renin inhibitor Ro 42-5892 was given by gavage repeatedly to rats receiving human renin at 40 ng/h. Ro 42-5892 lowered blood pressure promptly to basal values. High human renin hypertension in this model is dose dependent, features a steeper relationship between blood pressure and plasma renin activity over time, and is associated with tachycardia and increased drinking. We conclude that the human angiotensinogen transgenic rat offers new perspectives in the study of human renin-induced hypertension.

Angiotensinogen↗

Vasopressor responses and hyperthermia by intracerebroventricular injections of penicillin, a pyrogen, in rats: involvement of brain angiotensin II.

Because hypothalamus is a center for both the blood pressure and thermoregulation, we assumed that there is a close interrelationship between them. To prove this hypothesis, effects of intracerebroventricular (ICV) injections of a pyrogen, penicillin-G (Pc), on the blood pressure and rectal temperature (RT) were investigated. The ICV injections increased the mean arterial pressure (MAP), heart rate (HR) and the abdominal sympathetic activity (SNA) dose-dependently in urethane-anesthetized rats. In conscious rats, Pc (100 U) elicited the two components of rises in MAP (+19 +/- 1 and +20 +/- 1 mm Hg), and both the RT and HR increased corresponding to the second phase of MAP responses (+1.0 +/- 0.1 degree C and +60 +/- 7 beats/min). ICV injections of an angiotensin II (ang II) antagonist significantly decreased the MAP (-30 +/- 4 mm Hg), HR (-106 +/- 13 beats/min), and the RT (-0.9 +/- 0.1 degree C). ICV injections of Pc elicited drinking behavior (the vehicle group; 1.1 ml/90 min vs Pc group; 8.6 ml) in rats water-deprivated for 24 hours. In spontaneously hypertensive rats (SHRs), ICV injections of Pc elicited augmented responses in the first phase but diminished in the second pressor phase. ICV injections of an ang II antagonist elicited augmented effects in both the MAP (-39 +/- 1 mm Hg) and RT (-0.8 +/- 0.1 degree C) in SHRs. Thus, RT fluctuated corresponding to the blood pressure level in the latter phase, where a brain ang II mechanism may be involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗