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Biomedical subjects

J Harting

Publications and source records attributed to J Harting.

27 records · Page 2Linked to original sources
PubMed1986

Antagonistic effects of bisoprolol on several beta-adrenoceptor-mediated actions in anaesthetized cats.

The beta-adrenoceptor antagonistic activity of i.v. administered bisoprolol ((+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy] -3-isopropylamino-2-propanol, hemifumarate) was studied under two different sets of experimental conditions in anaesthetized cats and compared to the activity of atenolol and propranolol. The responses of several target organs to beta 2-adrenoceptor stimulation were used: inhibition of isoprenaline effects on diastolic blood pressure, hindlimb perfusion pressure, soleus muscle contractility and histamine aerosol-induced bronchoconstriction. The inhibition of isoprenaline-induced tachycardia served as indicator of beta 1-antagonism. The slopes of agonist dose ratio vs. antagonist dose effect were close to unity for propranolol but deviated from unity for atenolol and even more so for bisoprolol. In spite of the ensuing difficulty of comparisons, bisoprolol showed the most pronounced selectivity indices (10-20), followed by atenolol (1-7.5) and propranolol (0.3-1.6). Thus, bisoprolol exhibited a higher degree of beta 1-selectivity in the cat than did atenolol, regardless of the parameter used for measurement of beta 2-antagonism. Propranolol proved to be non-selective or even had a somewhat higher affinity for beta 2- than for beta 1-adrenoceptors.

Anesthesia↗
PubMed1986

Altered light/dark activity difference with aging in two rat strains.

The daily activity rhythm of adult and senescent male rats of two different strains (Iva:SDIV and Emd:Wi-AF/Han) was evaluated over several days with a capacitance-induction motility monitor. The Iva:SDIV rats were 6 to 9 or 29 to 32 months old and the Emd:Wi-AF/Han rats were 3 to 5, 16 to 18, or 31 to 39 months old at the time of testing. The rats were maintained in individual cages under a 12:12 hr light/dark regimen prior to and during this experiment. Senescent rats were much less active during the dark phase and somewhat more active during the light phase than same-strain young adult rats. This pattern of results was found for measurement of gross and fine movements combined (high sensitivity setting) and to a lesser extent for gross movements alone (low sensitivity setting). Furthermore, in the senescent rats the absolute magnitude of the light/dark activity difference was found to be positively related to the subsequent survival time.

Aging↗
PubMed1986

Avoidance acquisition in adult and senescent rats.

Male rats aged 6, 19, or 33 months were trained successively in one- and two-way avoidance tasks. The one-way avoidance test consisted of up to 30 trials given in a single session with the conditional stimulus (CS; 14-kHz tone) presented for either 3 s or for 10 s in separate groups. Senescent rats performed poorest, middle-aged rats intermediately, and young adult rats best. Failure of the longer CS to yield better acquisition than the short CS in the senescent group suggested that the age-related deficit probably did not result from slower responding. In subsequent shuttle box training there was no appreciable age difference in achieving the learning criterion. A compound visual-auditory CS was used, and in further evaluation of well-trained rats it was found that the auditory component was much more effective than the visual component in eliciting avoidance. However, this differential effect of the two stimuli was much weaker in the senescent group than in the young adult group. Nonetheless, these same senescent and adult rats readily learned to make avoidance responses using only the auditory CS, demonstrating that this was an effective stimulus for all age groups.

Aging↗
PubMed1986

Pharmacodynamic profile of the selective beta 1-adrenoceptor antagonist bisoprolol.

The pharmacodynamic activity of (+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropylamino-2- propranol- hemifumarate (bisoprolol, EMD 33 512) has been investigated under in vitro and in vivo conditions. Bisoprolol was found to be an effective beta-adrenoceptor antagonist, the pA2 values determined against isoprenaline in guinea pig atria and tracheal muscle being 7.45 and 6.41, respectively. Thus, the selectivity ratio of bisoprolol in favour of beta 1-adrenoceptors is 11. Inhibition of the isoprenaline-induced tachycardia in guinea pigs indicated a long duration of action for bisoprolol. The compound was devoid of intrinsic sympathomimetic activity as shown by the lack of effect on heart rate in anaesthetized and reserpine pretreated rats. Studies in rabbits and guinea pigs revealed a local anaesthetic activity of bisoprolol at high concentrations. Bisoprolol protected the hearts of anaesthetized dogs against the sequelae of intermittent coronary occlusions, as judged by the reduction of the ST-segment elevation in the epicardial ECG. Bisoprolol exerted a blood pressure lowering effect in conscious renal hypertensive dogs after oral administration of 30 micrograms/kg. There was no indication of any action on the CNS in monkeys following an oral dose of up to 8 mg/kg.

Adrenergic beta-Antagonists↗
PubMed1985

Drug induced hypothermia in adult and senescent rats.

Temperature regulation was evaluated in senescent (34-40 month old) and adult (8-9 month old) female Iva:WIWU and Emd:Wi-AF/Han rats. Injection of 1.5 mg/kg BW apomorphine HCl or 1.0 mg/kg BW oxotremorine sesquifumarate produced comparable maximal hypothermic responses in adult and senescent rats. However, the latency to reach maximal hypothermia after oxotremorine (but not apomorphine) was longer in senescent than in adult rats of both strains.

Aging↗
PubMed1985

Drinking by senescent and adult rats in response to regulatory challenges.

The regulation of water and electrolyte balance was elevated in senescent (greater than 31 months) and adult (5-10 months) rats of several strains. Weekly food and water intake, drinking induced by 24-hr water deprivation and drinking induced by injection of hypertonic saline were roughly the same in old and adult rats. However, senescent rats drank less after injection of the beta-adrenergic agonist isoprenaline than adult rats. There were no appreciable strain differences in drinking in response to these regulatory challenges although baselines sometimes differed between strains.

Aging↗
PubMed1976

Effects of pentobarbital and d-amphetamine on the repeated acquisition of response sequences by pigeons.

Pigeons were trained to acquire a new 4-response sequence in each session by pecking three keys in a predetermined order. The key color varied for each step under the chained schedule, but there was only one key color under the tandem schedule. Under the reset contingency, incorrect responses produced a reset of the 4-response sequence to its beginning and a short timeout. In the non-resent contingency, only the timeout was produced by incorrect responses. Under both contingencies of both schedules, low doses (3-10 mg/kg) of pentobarbital increased the response rate and the total number of errors, although the rate increases usually occurred at lower doses than did the increases in errors. A dose of 17.5 mg/kg pentobarbital eliminated almost all responding. Injection of low doseas (0.1 -0.3 mg/kg) of d-amphetamine decreased the total number of errors under both contingencies of both the chained and the tandem schedules. Higher doses of d-amphetamine sometimes increased the total number of errors and decreased the response rate.

Animals↗
PubMedDate not supplied

Beta 1-selectivity of bisoprolol, a new beta-adrenoceptor antagonist, in anesthetized dogs and guinea pigs.

The beta-adrenoceptor activity of the newly synthesized antagonist bisoprolol [+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropylamino-2- propranol, hemifumarate), has been compared with the effect of several reference compounds in anesthetized dogs and guinea pigs. In anesthetized, bivagotomized dogs, isoprenaline dose-response relations for increase in heart rate and decrease in diastolic blood pressure were established. Bisoprolol had the largest beta 1/beta 2 ratio, i.e., 147 (102-292). Practolol showed a beta 1/beta 2 ratio greater than 17; betaxolol 6-15; acebutolol, atenolol, and metoprolol 1.1-3.2; mepindolol 0.6-1 and propranolol 0.2. In artificially ventilated guinea pigs, the activity of bisoprolol on histamine-induced increase in tracheal lateral pressure (TLP) and basal heart rate (HR) was tested: using doses taken at TLP (30 mm Hg) and HR (250 beats/min), bisoprolol exhibited the most pronounced ratio TLP/HR of 124 +/- 59, followed by atenolol 33 +/- 23, metoprolol 25 +/- 15, betaxolol 12 +/- 4, propranolol 1 +/- 0.3, and celiprolol 0.23 +/- 0.19. These experiments indicate that bisoprolol possesses a pronounced beta 1-selectivity, which seems to be superior to that of known beta 1-selective antagonists.

Adrenergic beta-Antagonists↗