Antihypertensive therapy and quality of life: a comparison of atenolol, captopril, enalapril and propranolol.

This randomized, double-blind parallel study compared the effects of atenolol, captopril, enalapril and propranolol in 360 men with mild-to-moderate essential hypertension. Patients were titrated until diastolic blood pressure (Korotkoff phase V) decreased by at least 10 mmHg or to 90 mmHg or less. Quality of life assessments, based on validated psychometric questionnaires and objective measurements of cognitive function, occurred after three study phases: placebo run-in (3-5 weeks), titration (1-4 weeks), and maintenance (4 weeks). After four weeks of maintenance therapy, atenolol, captopril and enalapril generally had equivalent effects on quality of life, as measured by psychometric questionnaires, whereas propranolol consistently evidenced worsening or less improvement. Global scores of distressing psychological symptoms differed as a function of specific treatment (P = 0.01), with improvements significantly better for the atenolol, captopril and enalapril groups as compared with the propranolol group. There were no statistically significant differences among treatments for changes in cognitive function at maintenance. Thus, the quality of life questionnaires differentiated among drugs of the same class, indicating that selection among antihypertensive drugs should be based on their specific qualities, not on general class characteristics.

Foraging choice in laboratory rats: Constant vs. variable delay.

Deprived animals choosing between a variable delay (with mean t ) and a constant delay of t s prior to availability of food usually prefer the variable delay. Models of discounted future rewards predict such preference. For comparison we write a model assuming that a forager minimizes the probability that its total food intake falls short of a fixed requirement. This model predicts preference for the constant delay at sufficiently high average feeding rates. In a test of the models, laboratory rats (Rattus norvegicus ) chose between a constant t s delay and a variable option with equiprobable delays of 1 and (2t -1)s. Each subject was presented with the same sequence of mean delays. Each delay was experienced by the subjects for seven consecutive test days. Between the first and the fourth test day, a subject's body weight was decreased from 85 to 75 percent of free- feeding weight. Between the fourth and the seventh test day, a subject's body weight was increased to 85 percent of free-feeding weight. As t increased from 5 to 50 s, subjects first preferred the constant delay and then came to prefer the variable delay. Thereafter, as t was decreased to 5 s, subjects retained preference for the variable delay, but the strength of that preference declined at t decreased. Short-term variation in body weight, at a given value of t , did not influence preference significantly. Despite the rats' initial preference for constant delays, we tentatively conclude that our results appear more consistent with the discounting model than with the energy budget model.

Visual function measured by reflex modification in rats with inherited retinal dystrophy.

Developmental changes in visual function were studied in the Royal College of Surgeons (RCS) rat with inherited retinal degeneration by examining the inhibition of acoustic startle reflexes by visual prestimuli. Compared with a congenic strain of nondystrophic rat, the RCS rats showed an increase in the interstimulus interval between the inhibitory prestimulus and the eliciting stimulus that produced maximal inhibition, a result suggesting a decrease in the speed of processing. The amount of inhibition also decreased over time, which suggests a progressive loss of visual function. Simultaneous presentation of auditory and visual prestimuli was used to demonstrate that the changes in inhibition were related to alterations in visual function and that auditory function was not impaired in these rats. The results show that reflex modification is a suitable test for evaluating visual dysfunction in rats.

Reflex modification as a test for sensory function.

Reflex modification is a versatile procedure for the assessment of sensory function because it can provide information about the responses of several sensory systems to both weak and intense stimuli. The procedure has two elements: The elicitation of some reflex, such as the acoustic startle reflex, and the modification of that reflex by preliminary stimuli. In these experiments we used reflex modification and reflex elicitation procedures to examine the normal development of auditory function in rats and to evaluate alterations in auditory function produced by physical and toxic insult. Adult rats exposed to octave bands of noise demonstrated frequency-specific deficits on a test of reflex modification, but not reflex elicitation. In the studies of developing rats, reflex elicitation appeared by postnatal day 12 and modification around day 14. Frequency-specific increases in both measures suggested that the phenomena were sensitive to auditory development and, not simply, motor development. Exposure to kanamycin on postnatal days 8 to 16 produced dose-related deficits in the ability to detect stimuli at 32 and 16 kHz, but not 4 and 0.8 kHz. These effects were observed in the absence of changes in reflex elicitation. The results demonstrate that reflex modification procedures provide more sensitive and specific information than that provided by the use of reflex elicitation alone.

Cutaneous and auditory function in rats following methyl mercury poisoning.

Rats were given a total dose of 50 mg/kg (Exp. 1), 13.3 or 40 mg/kg (Exp. 2), or 40 mg/kg (Exp. 3) of methyl mercury chloride subcutaneously over a course of 5 days. At varying times after the toxic exposure, up to 1 year, their sensory functioning was assessed by reflex modulation methods: stimuli of interest were presented just before an intense tone which elicited the startle reflex, and stimulus reception was measured by the inhibitory control of the stimuli over the amplitude of the reflex. In Experiment 1 cutaneous prestimuli (electric shock to the tail) and brief acoustic transients (silent periods in noise) were less effective inhibitors of reflex activity in poisoned animals, compared to controls, indicating that the poisoned animals had impairments in cutaneous sensitivity and audition. In Experiment 2 the time course of sensory loss and subsequent recovery was studied. Impaired auditory function was shown further by a deficit in the effectiveness of weak noise pulses, and, in addition, the cutaneous deficit for weak tail shocks was accompanied by an exaggerated or hyperpathic response to more intense tail shocks. Experiment 3 confirmed the finding that the loss of sensitivity to weak shock was accompanied by an enhancement of the response to more intense shock. These data were related to peripheral neuropathy and shown to be analogous to certain clinical symptoms of Minamata disease reported in humans.

Acute exposure to methyl or ethyl alcohol alters auditory function in the rat.

Effects of alcohol on audition were studied in the rat by examining the modification of acoustic startle reflexes by pure tone pulses and by gaps in white noise. Systematic inhibition of the startle reflex by variation in pulse intensity provides an objective measure of loudness perception, while variation in gap duration assesses temporal acuity. Groups of rats (n = 8) received four injections of 0.0, 0.25, 1.00, and 2.00 g/kg of either methyl or ethyl alcohol in increasing order at 1-hr intervals. One-half hour after the administration of each dose, loudness perception or temporal acuity was measured. Blood alcohol levels (mM) for the two alcohols obtained in control animals were equivalent following the final dose. Alcohol produced a dose-dependent reduction in baseline startle amplitude that was greater during exposure to ethanol than during methanol. Loudness functions associated with pulse intensity were not diminished by alcohol; however, inhibition produced by a gap in noise was reduced following the highest dose of either alcohol. These data are consistent both with behavioral studies that have suggested that alcohol does not affect loudness perception, and with electrophysiological experiments which indicate that alcohol disrupts temporal relationships along the primary auditory pathway.

Interrelationships among activity, food intake and weight gain in genetically obese and lean Zucker rats.

In Experiment 1, food deprivation resulting in a 30% reduction in body weight produced significant increases in wheel running in both obese and lean female Zucker rats. In Experiment 2, a new technique, food contingent activity (FR, VI), dramatically increased wheel running in both obese and lean female Zucker rats. This increase in activity was achieved primarily during the dark period. Regardless of changes in activity levels, food intake and body weight gain remained similar to controls. When food was again available ad lib, activity levels rapidly decreased for obese but not lean rats. These results indicate that behavioral interventions alone are not sufficient to correct the obesity of the genetically obese rat.