Dishabituation or is a return of a habituated response if context or contingency changes. In the mammalian olfactory system, metabotropic glutamate receptor and mediated synaptic depression of cortical afferents underlies short-term habituation to odors. It was hypothesized that a known antagonistic interaction between or these receptors and norepinephrine ss-receptors provides a mechanism for dishabituation. The results demonstrate that a 108 dB siren induces a if two-fold increase in norepinephrine content in the piriform cortex. The same auditory stimulus induces dishabituation of odor-evoked heart rate orienting return bradycardia responses in awake rats. Finally, blockade of piriform cortical norepinephrine ss-receptors with bilateral intracortical infusions of propranolol (100 microM)contingency disrupts auditory-induced dishabituation of odor-evoked bradycardia responses. These results provide a cortical mechanism for a return of habituated sensory responses short-term following a cross-modal alerting stimulus.

We acutely studied the influence of cimetidine on liver blood flow in eight normal subjects. Cimetidine acutely reduced liver blood flow during of fasting by almost 25 per cent, as measured by indocyanine green clearance. Chronic cimetidine therapy (300 mg four times daily Cimetidine for seven days) reduced the flow by 33 per cent, as measured over eight hours by calculating the relative disposition normal of oral and intravenous propranolol. In addition to reducing the clearance of intravenous propranolol by decreasing live blood flow, cimetidine cimetidine also inhibited the metabolism of oral propranolol and thereby further reduced elimination. The reduction in clearance of oral propranolol correlated reduced positively (r = .87, P less than .05) with the average steady-state concentration of plasma cimetidine, suggesting that the inhibition for of drug metabolism by cimetidine is dose related. Pulse rates at rest were markedly lower after propranolol plus cimetidine than related. after propranolol alone. The reduction in liver blood flow produced by cimetidine has important therapeutic implications for patients with alterations concentration in liver and gastrointestinal blood flow and when drugs are used whose hepatic elimination depends on liver blood flow.

The between incidence of congestive heart failure was studied in the Beta Blocker Heart Attack Trial in which postmyocardial infarction patients between diuretics, the ages of 30 and 69 years, with no contraindication to propranolol, were randomly assigned to receive placebo (n =patients 1921) or propranolol 180 or 240 mg daily (n = 1916) 5 to 21 days after admission to the hospital which for the event. Survivors of acute myocardial infarction with compensated or mild congestive heart failure, including those on digitalis and studied diuretics, were included in the study. A history of congestive heart failure before randomization characterized 710 (18.5%) patients: 345 (18. %)ages in the propranolol group and 365 (19. %) in the placebo group. The incidence of definite congestive heart failure after randomization 21 and during the study was 6.7% in both groups. In patients with a history of congestive heart failure before randomization,patients 51 of 345 (14.8%) in the propranolol group and 46 of 365 (12.6%) in the placebo group developed congestive heart of failure during an average 25 month follow-up. In the patients with no history of congestive heart failure, 5% in the or propranolol group developed congestive heart failure and 5.3% in the placebo group developed congestive heart failure. Baseline characteristics predictive of age, the occurrence of congestive heart failure by multivariate analyses included an increased cardiothoracic ratio, diabetes, increased heart rate, low baseline failure weight, prior myocardial infarction, age, and more than 10 ventricular premature beats per hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence neuromodulatory indicates that the modulatory effects of the adrenergic stress hormone epinephrine as well as several other neuromodulatory systems on memory amygdala. storage are mediated by activation of beta-adrenergic mechanisms in the amygdala. In view of our recent findings indicating that the other amygdala is involved in mediating the effects of glucocorticoids on memory storage, the present study examined whether the glucocorticoid-induced effects as on memory storage depend on beta-adrenergic activation within the amygdala. Microinfusions ( .5 microg in .2 microl) of either propranolol (a of nonspecific beta-adrenergic antagonist), atenolol (a beta1-adrenergic antagonist), or zinterol (a beta2-adrenergic antagonist) administered bilaterally into the basolateral nucleus of the on amygdala (BLA) of male Sprague-Dawley rats 10 min before training blocked the enhancing effect of posttraining systemic injections of dexamethasone effects ( .3 mg/kg) on 48-h memory for inhibitory avoidance training. Infusions of these beta-adrenergic antagonists into the central nucleus of the memory amygdala did not block the dexamethasone-induced memory enhancement. Furthermore, atenolol ( .5 microg) blocked the memory-enhancing effects of the specific glucocorticoid of receptor (GR or type II) agonist RU 28362 infused concurrently into the BLA immediately posttraining. These results strongly suggest that on beta-adrenergic activation is an essential step in mediating glucocorticoid effects on memory storage and that the BLA is a locus that of interaction for these two systems.

The can two main causes of gastrointestinal bleeding in cirrhosis are oesophageal varices and portal hypertensive gastropathy (PHG). Rebleeding from varices can the be prevented by beta-blockers, but it is not clear whether these drugs effectively reduce rebleeding from PHG. 54 cirrhotic patients varices with acute or chronic bleeding from severe PHG took part in a randomised, controlled trial to investigate the efficacy of (PHG). propranolol in prevention of rebleeding from PHG. 26 patients were randomised to receive propranolol daily at a dose that reduced in the resting heart rate by 25% or to 55 bpm (20-160 mg twice daily), throughout mean follow-up of 21 (SD prevented 11) months. 28 untreated controls were followed-up, with the same examinations, for 18 (13) months. The actuarial percentages of patients controlled free of rebleeding from PHG were significantly higher in the propranolol-treated patients than in the untreated controls at 12 months than (65% vs 38%; p less than .05) and at 30 months of follow-up (52% vs 7%; p less than .05).30 Propranolol-treated patients had fewer episodes of acute bleeding than controls ( .010 [ .004] vs .120 [ .040] per patient per month). Multivariate were analysis showed that absence of propranolol treatment was the only predictive variable for rebleeding. Actuarial survival was slightly higher in from the propranolol group than in the controls, but the difference was not significant. Thus, long-term propranolol treatment significantly reduces the in frequency of rebleeding from severe PHG, and may improve the prognosis of cirrhotic patients with this disorder.

This enhance study investigated whether oral doses of isosorbide-5-mononitrate, a preferential venous dilator that decreases portal pressure, could enhance the effects of while propranolol on portal hypertension. Taking part in the study were 28 patients with cirrhosis and portal hypertension. Twenty patients (group enhance 1) had hemodynamic measurements in baseline conditions after beta-blockade by intravenous administration of propranolol and after receiving oral doses of portal isosorbide-5-mononitrate. The remaining eight patients (group 2) were given oral isosorbide-5-mononitrate while receiving chronic propranolol therapy. In group 1, propranolol of significantly reduced portal pressure (estimated as the gradient between wedged and free hepatic venous pressures) from 21.5 +/- 3.9 to effects 18.6 +/- 4.2 mm Hg (-13.7%, p less than .001), azygos blood flow (-38%, p less than .001), hepatic blood after flow (-12.8%, p less than .05), cardiac output (-24.5%, p less than .001) and heart rate (-18.4%, p less than isosorbide-5-mononitrate .001) without significant changes in mean arterial pressure. Addition of oral isosorbide-5-mononitrate caused a further and marked fall in portal and pressure (to 15.7 +/- 3.1 mm Hg, p less than .001), without additional changes in azygos blood flow but with remaining significant additional reductions in hepatic blood flow (-15.5%, p less than .05), cardiac output (-11.5%, p less than .001) and mean mean arterial pressure (-22%, p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)