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Biomedical subjects

T C Hamilton

Publications and source records attributed to T C Hamilton.

At least 163 records · Page 9Linked to original sources
PubMed1981

Involvement of the adrenal glands in the hypotensive response to bromocriptine in spontaneously hypertensive rats.

1 The dopamine agonist, bromocriptine, produced a hypotensive response following oral administration to conscious normotensive and spontaneously hypertensive (SH)-rats. 2 In SH-rats the dose-related falls in blood pressure to bromocriptine, 3 to 30 mg/kg orally or intraperitoneally, were biphasic, an initial fall at 1 h being followed by some recovery at 2 h and a subsequent fall in blood pressure at 4 and 6 h. 3 The dopamine antagonists, metoclopramide, sulpiride, haloperidol and pimozide, had little or no effect on the hypotensive response to bromocriptine, 10 mg/kg orally, in SH-rats. 4 Pretreatment with alpha-methyl-p-tyrosine augmented the hypotensive response to bromocriptine, 10 mg/kg orally, in SH-rats. 5 In adrenal demedullated SH-rats, the hypotensive response to bromocriptine, 3 to 30 mg/kg orally, was abolished. 6 In SH-rats the hypotensive response to bromocriptine, 10 mg/kg orally, was prevented by the beta-adrenoceptor blocking drugs, propranolol and oxprenolol, but was unaffected by (+)-propranolol and by the cardio-selective beta-adrenoceptor blocking drug, atenolol. 7. In SH-rats pretreated with bromocriptine, 10 mg/kg orally, and then anaesthetized, the pressor responses to low doses of intravenous adrenaline were reversed to depressor, indicating that bromocriptine possesses alpha-adrenoceptor blocking activity. 8 The results suggest that hypotensive response to bromocriptine in conscious SH-rats is mediated by adrenaline released from the adrenal medullae which, in the presence of alpha-adrenoceptor blockade, stimulates vascular beta-adrenoceptors producing vasodilatation.

Adrenal Glands↗
PubMed1981

Androgen and oestrogen binding in cytosols of human ovarian tumours.

The specific retention of androgens and oestrogens by cytoplasmic components of human ovarian tumours was investigated. High-affinity, low-capacity binding of androgens was observed in 88% of tumour specimens and oestrogen binding in 32%. Retention of oestrogens did not occur in the absence of androgen binding. The androgen-binding component, of sedimentation coefficient 7.5-8.5S, showed specificity for 5 alpha-dihydrotestosterone and 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-trien-3-one (R1881). In some instances, competition for R1881-binding sites indicated the presence of progesterone receptor-like binding. The data presented suggest strongly the existence of androgen and oestrogen receptors in some ovarian tumours and may be relevant to histopathological classification and therapeutic rationales.

Androgens↗
PubMed1980

Cyclic nucleotides and central cardiovascular control in the conscious cat.

When infused into the third ventricle of the brain of the conscious cat, the phosphodiesterase inhibitors, papaverine and aminophylline, increased blood pressure and heart rate whilst the phosphodiesterase stimulator, imidazole-4'-acetic acid, decreased blood pressure. Administered intravenously, these compounds caused the opposite effects indicating that the responses after third-ventricular administration were centrally mediated. Infused of dibutyryl cyclic 3',5'-AMP into the third ventricle increased blood pressure and heart rate, whereas dibutyryl cyclic 3',5'-GMP had little effect and antagonised and pressor response to dibutyryl cyclic 3',5'-AMP. ATP, 5'-AMP and adenosine induced similar changes to dibutyryl cyclic 3',5'-AMP, although the pressor responses to these compounds were of different onset and/or duration. When administered into the third ventricle both alpha- and beta-adrenoceptor blocking agents reduced the pressor response caused caused by the phosphodiesterase inhibitor, papaverine, given by the same route. These results demonstrate a central effect of adenosine and adenosine nucleotides to raise blood pressure. The possibility of a specific role for cyclic 3',5'-AMP in the central control of blood pressure is discussed.

Adrenergic alpha-Antagonists↗
PubMed1980

Comparison of the anti-hypertensive response to beta-adrenoceptor blocking drugs in intact and adrenal-demedullated spontaneously hypertensive rats.

1 The beta-adrenoceptor blocking drugs atenolol, metoprolol, practolol, propranolol, timolol and oxrenolol (as racemates) were administered acutely at three dose levels (0.01, 0.03 and 0.1 mmol/kg i.p. or s.c.) to spontaneously hypertensive rats with intact adrenal glands (SH-rats) and following unilateral adrenalectomy and contralateral adrenal-demedullation (SHAD-rats). Changes in mean arterial pressure and heart rate were determined via an indwelling aortic catheter, with the animals placed in a quiet environment. 2 All drugs significantly lowered the blood pressure of SHAD-rats, and these responses were not always associated with changes in basal heart rate. 3 With the exception of metoprolol and atenolol, the beta-adrenoceptor blocking drugs were less effective as anti-hypertensives in SH- than in SHAD-rats. Notably, timolol and oxprenolol lowered the blood pressure of SH-rats at low doses only, whereas propranolol evoked a pressor response in this model. 4 Whilst (+)-propranolol lowered the blood pressure of SHAD-rats only at a dose which caused myocardial depression, the anti-hypertensive response to (--)-propranolol did not parallel changes in heart rate and was preceded by a pressor response. 5 The results imply that adrenal catecholamine release contributes towards masking the anti-hypertensive effects of some beta-adrenoceptor antagonists in SH-rats.

Adrenal Medulla↗
PubMed1979

Ribonucleic acid in plasma from normal adults and multiple myeloma patients.

Reports of the presence of RNA in human plasma have been numerous, often suggesting that RNA in plasma is correlated with human disease. We critically examined the methods for determination of RNA in plasma. Lack of method specificity has caused previous workers to overestimate plasma RNA concentrations by more than 50-fold. To isolate RNA from plasma, we used both a phenol-chloroform extraction and a modified Schmidt-Thannhauser procedure. We show that RNA in plasma can be identified and quantified by alkaline hydrolysis of the plasma extract and subsequent separation of the resulting 2'- and 3'-mononucleotides by "high-performance" liquid chromatography. We could not detect RNA in plasma from either apparently healthy, normal adults or multiple myeloma patients, but found 1.1 mg/L in the plasma of a patient with Waldenström's macroglobulinemia. Our method is useful for the specific determination of RNA in plasma and will detect as little as 600 micrograms/L.

Chromatography, High Pressure Liquid↗
PubMed1978

Diminishing hypotensive effect of increasing doses of pindolol in DOCA/saline hypertensive rats.

In DOCA-saline hypertensive rats, pindolol (4, 20 or 50 mg/kg orally) produced a hypotensive effect which was inversely related to dose. Following adrenal demedullation, a hypotensive response to the highest dose of pindolol was unmasked and the magnitude of the responses to lower doses was increased. The results suggest that adrenal catecholamines moderate the hypotensive effects of high doses of pindolol.

Adrenalectomy↗
PubMed1977

Measurements of contraction latencies to mechanical and electrical stimulation of the protozoan, Spirostomum ambiguum.

Measurements made on contraction latencies in Spirostomun suggest that mechanical stimulation causes contractions to be initiated by the release of small amounts of calcium from a store tightly coupled to the contractile apparatus. Contraction to electrical stimulation appears to result from the gross electrophoretic mobilization of large amounts of calcium from a loosely coupled store. Contraction latencies to mechanical stimulation were three milliseconds and were independent of stimulus strength, previous stimulation, and contraction probability. For 0.5-millisecond biphasic electrical stimulation the contraction latencies varied widely. Latencies to initial contractions were dependent on stimulus strength: from 1.0 milliseconds for a stimulus that caused a 100% probability of contraction to 2.0 milliseconds for a stimulus that caused a 10% probability of contraction. Latencies of contraction to electrical stimulation were also dependent upon previous stimulation, lengthening to over 300 milliseconds after ten minutes of stimulation. Initial contraction latencies were not affected by previous stimulation to the other (electrical or mechanical) stimulus modality. Repeated electrical stimulation also reduced the animal's resting length and slowed the rate of post contraction re-extension, whereas mechanical stimulation did not have these effects.

Animals↗
PubMed1977

Electron microbeam analysis of calcium distribution in the ciliated protozoan, Spirostomum ambiguum.

Electron microprobe analyses of calcium distribution in the ciliated protozoan, Spirostomum ambiguum, indicated several calcium rich sites. One site was an endoplasmic distribution of calcium coincident with phosphorus which corroborates previous findings of hydroxyapatite deposits within Spirostomum. These apatite deposits were distributed throughout the endoplasm, but not within the nuclei or the contractile vacuole. Calcium was also detected within the cortical region. Cortical calcium was in greater concentration in the anterior portion of the organism and decreased towards the posterior end (region containing the contractile vacuole). Phosphorus and potassium were also detected as gradients from the anterior end, whereas magnesium was detected in the same density throughout the cortical region. Line scans of cortical regions suggested (1) distributions of calcium within mitochondria and/or vesicles, and (2) calcium associated with bundles of microfilaments.

Animals↗
PubMed1977

Studies on the cardiovascular effects of pindolol in DOCA/saline hypertensive rats.

1 A hypotensive response to orally administered pindolol in conscious normotensive and deoxycorticosterone acetate (DOCA)/saline hypertensive rats (DS-rats) is described. In DS-rats, pindolol (10-50 mug/kg) produced a dose-dependent fall in blood pressure and elevation of resting heart rate.2 The hypotensive response and tachycardia produced by oral pindolol (50 mug/kg) in DS-rats were prevented by propranolol (5 mg/kg), suggesting that pindolol's effects are mediated by beta-adrenoceptor stimulation.3 After mecamylamine (10 mg/kg), oral pindolol (50 mug/kg) produced a further fall in blood pressure in DS-rats, suggesting that its hypotensive effects are probably mediated in the peripheral vasculature.4 Pretreatment with oral pindolol (10 or 50 mug/kg) resulted in a reduction of neuronally-induced tachycardia in pithed DS-rats; neuronally-evoked pressor effects were also antagonized by pindolol (50 mug/kg, orally).5 Whereas pindolol, 50 mug/kg orally or intraperitoneally, produced a marked and progressive hypotensive response of rapid onset (20 min) in DS-rats the same dose intravenously produced a smaller response of delayed onset (80 minutes).6 In anaesthetized DS-rats, an equivalent degree of cardiac beta-adrenoceptor blockade was produced by pretreatment with pindolol, 50 mug/kg orally (2 h previously) or intravenously (1 h previously).7 After administration of pindolol, 2 mg/kg intravenously, to conscious DS-rats, the tachycardia produced by intravenous isoprenaline, 3 mug/kg, was almost abolished for the first 60 min of the study, whereas a hypotensive response to pindolol was delayed in onset (100 minutes).8 The hypotensive response and tachycardia produced by oral pindolol 50 mug/kg, in DS-rats were prevented by inhibition of metabolic enzyme activity by pretreatment with Proadifen (SKF 525-A), 80 mg/kg.9 The results suggest that pindolol's effects on blood pressure and heart rate in the conscious DS-rat are mediated by a metabolite(s) acting by stimulation of peripheral beta-adrenoceptors.

Administration, Oral↗
PubMed1977

Bufuralol, a new beta-adrenoceptor blocking agent in a series of benzofuran-2-ethanolamines. Part 2: pharmacology.

1-(7-Ethylbenzofuran-2-yl)-2-tert.-butylamino-1-hydroxyethane hydrochloride (bufuralol) is a non-selective beta-adrenoceptor blocking agent which closely resembles propranolol in its properties, including potency. Bufuralol is devoid of alpha-adrenoceptor blocking activity but possesses beta-adrenoceptor agonist activity. beta-Adrenoceptor blocking activity resides mainly in the (-)-isomer though membrane stabilising properties are associated with both optical isomers.

Adipose Tissue↗
PubMed1976

Effect of intracerebroventricular 5,6-dihydroxytryptamine on blood pressure of spontaneously hypertensive rats.

The effects of intracerebroventricular injections of 5,6-DHT on the development and maintenance of hypertension in spontaneously hypertensive rats has been investigated. 5,6-DHT, injected into 6 week old rats, retarded the development of hypertension for at least 6 weeks; this effect was not accompanied by inhibition of the pressor response produced by stimulation of the total peripheral sympathetic outflow. 5,6-DHT, injected into 14-15 week old rats with established hypertension, produced a short-lived fall in blood pressure. These findings suggest that central 5-HT neurones are involved in the development of hypertension in spontaneously hypertensive rats.

5,6-Dihydroxytryptamine↗
PubMed1976

Hypotensive responses following oral adminstration of beta-adrenoceptor blocking drugs to the conscious cat.

On oral administration, the non-selective beta-adrenoceptor blocking drugs (+/-)-bufuralol, (-)-bufuralol, propanolol, oxprenolol, pindolol and alprenolol produced hypotensive responses in the conscious cat; (+)-bufuralol was without effect. The selective beta-adrenoceptor blocking drugs practolol and atenolol had no effect on blood pressure but tolamolol elicited a hypotensive response. All the drugs tested reduced the tachycardia due to intravenous isoprenaline in the conscious cat; however, not all doses of these drugs reduced blood pressure. (+)-Bufuralol was devoid to beta-adrenoceptive blocking activity. Only tolamolol reduced the pressor response to i.v. phenylephrine in the conscious cat, indicating that alpha-adrenoceptive blocking activity may contribute to its hypotensive action. The results suggest that beta-adrenoceptive blocking activity is necessary for the hypotensive responses of these drugs. However, for the different drugs, there was no correlation between peripheral beta-adrenoceptive blocking activity and hypotensive response.

Adrenergic alpha-Antagonists↗