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Biomedical subjects

B A Berkowitz

Publications and source records attributed to B A Berkowitz.

At least 91 records · Page 5Linked to original sources
PubMed1984

Effects of the leukotrienes on the vasculature and blood pressure of different species.

We have examined in these studies the contractile activity of leukotrienes (LTs) C4, D4 and E4 on vascular ring segments obtained from several species and demonstrated that the distal segment of the guinea-pig pulmonary artery is a useful and convenient preparation for the study of LT vascular pharmacology. In vitro, LTs had no effect on aortic rings from rats, rabbits or guinea pigs. In contrast, LTs produced significant contraction of the distal portion of the pulmonary artery of the guinea pig. The rank of the contractile effects of LT was LTD4 = LTC4, greater than LTE4, with ED40 (molar) values of 6.1 X 10(-9), 1 X 10(-8) and 1.4 X 10(-6), respectively. Norepinephrine, serotonin and histamine were at least 50- to 100-fold less potent. Partial tolerance developed to the contractile action of LT in vitro. Vascular contraction produced by LTD4 was antagonized by a selective LT antagonist. No evidence for a relaxant action of LT was obtained as LTD4 and LTC4 failed to relax rabbit aorta or guinea-pig pulmonary arterial rings. The effects of LTD4 on hemodynamics in vivo were studied in anesthetized guinea pigs. LTD4 (0.1-10 micrograms/kg) significantly decreased cardiac output but increased pulmonary vascular resistance. To assess the activity of LTs in another species, the in vitro contractile response of monkey pulmonary artery was determined. LTD4 was also a potent contractile agent in this species with significant contraction obtained at 1 X 10(-9) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Catecholamine mechanisms in the stimulation of mouse locomotor activity by nitrous oxide and morphine.

Nitrous oxide, like morphine, produces a significant increase in mouse locomotor activity. This stimulation of locomotor activity is antagonized by the narcotic antagonist naloxone (10 mg/kg). The catecholamine synthesis inhibitor alpha-methyl-p-tyrosine (300 mg/kg) also significantly reduced the nitrous oxide stimulation of mouse locomotor activity. Administration of naloxone (10 mg/kg) to mice previously treated with alpha-methyl-p-tyrosine resulted in a further decrease in nitrous oxide stimulated activity levels. Haloperidol (0.08-0.64 mg/kg), a potent dopamine receptor antagonist, dose dependently reduced the activity stimulation resulting from exposure to nitrous oxide. Administration of haloperidol (0.08 mg/kg) in conjunction with naloxone (10 mg/kg) further reduced the nitrous oxide effect. In view of the fact that morphine's activity stimulating effects are reduced by alpha-methyl-p-tyrosine and haloperidol, the results reported here suggest additional similarities in the pharmacology of morphine and nitrous oxide. The stimulation of mouse locomotor activity produced by nitrous oxide appears to be mediated by both endogenous opioid and catecholamines.

Animals↗
PubMed1983

Dopamine and dopamine receptors as target sites for cardiovascular drug action.

It is controversial whether dopamine (DA) is a peripheral neurotransmitter in the cardiovascular/renal system. The endogenous concentration of DA in the heart and blood vessels is generally only a fraction (5%) of that of norepinephrine (NE). With perhaps the exception of the kidney, the majority of the evidence suggests a precursor role for this amine rather than that of a neurotransmitter. The main weakness of arguments favoring DA as a vascular neurotransmitter is relative lack of data showing selective DA release and lack of effects of selective DA antagonists on neural stimulation. However, DA receptors have been characterized in cardiovascular tissues and are of two types: DA1 receptors located on vascular smooth muscle (postjunctional), which appear to mediate relaxation of the muscle, and DA2 receptors located on sympathetic nerves (pejunctional), which inhibit NE release. These receptors are interesting and potential target sites for novel cardiovascular drug action for the treatment of hypertension and renal ischemia. Moreover, selective DA receptor agonists will be important tools in understanding the role of DA receptors in normal and disease states.

Animals↗
PubMed1982

Lack of an opiate response to nitrous oxide in mice resistant to the activity-stimulating effects of morphine.

Nitrous oxide, like morphine, stimulates locomotor activity in the CD-1, C-57 and C-3H mouse strains. This stimulation of locomotor activity is antagonized by the narcotic antagonist naltrexone (3 and 30 mg/kg). There are several strains (A/J and DBA/2J) of mice in which morphine does not stimulate locomotor activity. Mice resistant to this behavioral effect of morphine show a stimulation of locomotor activity in response to nitrous oxide which is not blocked by naltrexone. These results provide new data linking the effects of morphine and nitrous oxide. The opiate-like stimulation of activity produced by nitrous oxide may result from the release of endogenous opiate-like substances. Nitrous oxide causes a displacement of [3H]naloxone from brain opiate receptors labeled in vivo in the CD-1 mouse strain. In marked contrast to these results, nitrous oxide administration to the A/J and DBA/2J morphine-resistant strains failed to displace [3H]naloxone from opiate receptors labeled in vivo. Thus, variations in the response to nitrous oxide may not only be strain-dependent but possibly related to deficits in the response of or interaction with the endogenous opiate system.

Animals↗
PubMed1982

Characterization of vasopressin analgesia.

Vasopressin produced analgesia in mice as estimated by using abdominal constriction tests (ED50 8.5 micrograms/kg i.v.) or hot plate method (ED50 63 micrograms/kg i.v.). However, vasopressin (10 micrograms/kg i.v.) produced no depression of locomotor activity in mice. Vasotocin had slight analgesic action; oxytocin or norepinephrine had none and there was no direct correlation between pressor response and analgesia. The analgesic action was nonopiate in nature as it was uninfluenced by the narcotic antagonist naltrexone at 5 to 15 mg/kg, but it was reserved by a vasopressin antagonist. Intraventricular administration of vasopressin (1-10 micrograms/kg) to mice produced no significant analgesia, suggesting a primarily peripheral locus of analgesic action. Vasopressin may play a role as an endogeneous pain regulating substance.

Analgesics↗
PubMed1982

Catecholamines in the vasculature of the rat and rabbit: dopamine, norepinephrine, epinephrine.

A highly sensitive radioenzymatic assay for the measurement of catecholamines in small blood vessels was applied to the measurement of the levels of norepinephrine (NE), dopamine (DA) and epinephrine (E). The results showed the presence of NE, E and DA in all segments of rat or rabbit vascular tissue analyzed. The predominant catecholamine in the vasculature from both species was NE, and the contents of E and DA were similar for most vessels. Unexpectedly large concentrations of E were associated with rabbit blood vessels.

Animals↗
PubMed1980

Altered disposition of vascular catecholamines in hypertensive (DOCA-salt) rats.

The levels of norepinephrine (NE), dopamine (DA) and epinephrine (E) in the vasculature of hypertension (DOCA-SALT) and normotensive rats were determined by radioenzymatic assay. Significant decreases in the NE content of the mesenteric artery, renal artery and cardiac tissue from DOCA-Salt treated rats were found. In contrast the NE content of the inferior vena cava, abdominal aorta and mesenteric vein were not significantly decreased in the DOCA-Salt treated rats. There was no evidence of an altered disposition of DA and E in the vasculature of DOCA-Salt treated rats. The results of the study indicate that NE is selectively depleted in the cardiovascular system of this model of experimental hypertension and it is proposed that this property reflects different functional roles of individual elements of the vasculature in the DOCA-Salt hypertensive rat.

Animals↗
PubMed1980

Experimental diabetes: alterations in circulating dopamine-beta-hydroxylase and norepinephrine.

Dopamine-beta-hydroxylase (DBH) activity is increased at least 5-fold in the serum of rats with experimental diabetes produced by Streptozotocin or Alloxan. The increased DBH activity persisted for 7 months. Dialysis did not reduce the elevated activity. Based on a large increase in the maximal velocity of the enzyme reaction and immunoprecipitation studies, there appears to be increased amounts of DBH in the serum of diabetic rats. Thyroxin and triiodothyronine concentrations were reduced in diabetic serum but replacement doses of these hormones did not correct the high DBH activity. In contrast, adrenalectomy or insulin administration prevented the diabetes and elevations of circulating DBH. Circulating norepinephrine levels in arterial and venous blood were measured at 4 and 16 weeks after the onset of diabetes and elevated only in venous blood at the early time interval. In summary, circulating DBH levels were increased in experimental diabetes but did not correlate with circulating norepinephrine levels. Further studes are required to differentiate between the possibilities of increased sympathetic nervous system activity and altered DBH turnover in experimental diabetes.

Adrenalectomy↗
PubMed1979

Tolerance to nitrous oxide analgesia in rats and mice.

The purpose of these experiments was to characterize the nature of tolerance to the analgesic action of nitrous oxide. Analgesia was assessed in rats using a tail-flick latency test and in mice using an abdominal constriction test. Rats and mice were exposed to nitrous oxide, 75 per cent, the balance oxygen, continuously for 16--18 hours. On re-exposure to nitrous oxide 30 min later, these animals were found tolerant to nitrous oxide in that the analgesic response was decreased by at least 50 per cent. Animals tolerant to nitrous oxide were not tolerant to morphine. Morphine (0.25--1.5 mg/kg) produced equal degrees of analgesia in control and nitrous oxide-tolerant mice and rats. In contrast, rats made tolerant to morphine by repeated daily injections of as much as 400 mg/kg subcutaneously or by subcutaneous implantation of morphine pellets (75 mg, twice) showed a decreased analgesic response to nitrous oxide. Thus the cross-tolerance between nitrous oxide and morphine appears unique in that it is unidirectional.

Anesthesia, General↗
PubMed1978

Vascular relaxation, aging and thyroid hormones.

Previous work indicates vascular can be studied in vitro and that there is a marked age-associated decrease in the ability of rat aortic strips to relax in response to beta-adrenergic agonists. The present studies were aimed at better understanding the role of thyroid hormones in vascular relaxation and aging. Removal of the thyroid gland from young rats resulted in a decrease in the ability of isoproterenol to relax the aorta. Relaxation caused by nitroglycerin, a non-specific relaxant, was not impaired by thyroidectomy. In 22-month-old rats, isoproterenol caused no relaxation unless exogenous thyroid hormones were administered. Hypophysectomy seven months prior to testing improved the ability of thyroid hormones to restore isoproterenol relaxation of the aorta. The loss of relaxation with age could be due in part to a pituitary mediated loss of responsiveness of aortic tissue to thyroid hormones. The data provide new evidence for the importance of thyroid hormones in beta-adrenergic receptor mediated vascular relaxation and demonstrate that the loss of aortic relaxation with aging can be reversed.

Aging↗
PubMed1978

Adrenal origin of plasma catecholamines after decapitation: a study in normal and diabetic rats.

The concentrations of catecholamines and the activities of dopamine-beta-hydroxylase were measured in blood obtained from decapitated diabetic and aged-matched control rats. The activity of dopamine-beta-hydroxylase in blood from diabetic rats was much greater (5 fold) than that seen for control rats. For both diabetic and control rats, decapitation was accompanied by an increase in levels of adrenaline and noradrenaline with no change in the activity of plasma dopamine-beta-hydroxylase. The results are consistent with a predominantly adrenal origin of catecholamines and extra-adrenal origin of dopamine-beta-hydroxylase. The high activity of dopamine-beta-hydroxylase in diabetes indicates either an increased activity of the sympathetic nervous system or changes in dopamine-beta-hydroxylase turnover.

Adrenal Glands↗