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Biomedical subjects

T C Hamilton

Publications and source records attributed to T C Hamilton.

At least 181 records · Page 10Linked to original sources
PubMed1976

Prolonged effects of p-chlorophenylalanine on the blood pressure of conscious normotensive and DOCA/saline hypertensive rats.

1. In deoxycorticosterone acetate (DOCA) saline hypertensive rats a single dose of p-chlorophenylalanine methylester (PCPAME) (400 mg/kg i.p.) produced a significant fall in blood pressure (20-43 mmHg) which lasted for at least 8 days and was accompanied by a parallel depletion of brain stem 5-hydroxytryptamine (5-ht) but not of noradrenaline (NA). 2. In normotensive rats single doses of PCPAME (200 and 400 mg/kg i.p.) produced a significant hypotension (15-20 mmHg) after a latent period of 5 days. An initial pressor response (12 mmHg) was observed at the higher dose level only on day 3. 3. The hypotensive response to PCPAME (200 mg/kg i.p.) in normotensive rats was not modified by pretreatment with 5,6-dihydroxytryptamine (5,6-DHT; 50 mug i.c.v.) or 6-hydroxydopa (6-ohda; 3 X 250 mug intracerebroventricularly). 4. It is concluded that the hypotensive response to PCPAME in normotensive rats in independent of brain stem depletion of 5-HT and is probably not mediated by the formation of a false transmitter substance acting via central noradrenergic inhibitory pathways. The mechanism involved in the antihypertensive response to PCPAME in DOVA/saline hypertensive rats has yet to be defined.

Animals↗
PubMed1976

Hyperaemic responses in two vascular beds of the anaesthetised cat.

In the chloralosed cat reactive hyperaemia to vessel occlusion, and vascular escape associated with vasoconstriction produced by drugs, have been examined in the hindquarters and splanchnic region, and following periaterial mesenteric nerve stimulation in the splanchnic region. The hyperaemic responses were not of a purinergic nature or mediated by an acetylcholine, histamine, dopamine or beta-adrenoceptor stimulant-like substance, and were independent of adrenergic innervation. These responses may respresent a local mechanism by which the vasculature produces vasodilation in response to reduced blood flow.

Anesthesia↗
PubMed1975

Influence of anti-hypertensive drug treatment on vascular reactivity in spontaneously hypertensive rats.

1. The effect of prolonged anti-hypertensive drug treatment on the blood pressure of conscious spontaneously hypertensive rats (SH-rats), and of age-matched normotensive Sprague-Dawley rats was determined during the development of hypertension in SH-rats and in the early stages of established hypertension. A comparison of the vascular reactivity to noradrenaline (NA) and 5-hydroxytryptamine (5-HT) was also made in isolated perfused mesenteric artery preparations from treated and control SH- and Sprague-Dawley rats. 2. Chronic treatment from age 4 to 16 weeks with hydrallazine alone, or a combination of hydrallazine/hydrochlorothiazide/reserpine, ad libitum in the drinking water, prevented the development of hypertension in SH-rats and also reduced the vascular reactivity to NA and 5-HT in isolated vessel preparations from treated compared to control rats. 3. Similar drug treatments started in early established hypertension reduced blood pressure in SH-rats over the 12 week treatment period (from age 8 to 20 weeks) without affecting vascular reactivity to NA and 5-HT in the isolated vessel preparation. 4. Drug treatments had little effect on blood pressure of age-matched Sprague-Dawley rats and no effect on vascular reactivity to NA and 5-HT in the isolated perfused mesenteric artery preparation from treated compared to control rats. 5. These results indicate that the development of increased vascular reactivity and of hypertension in SH-rats occurs simultaneously and, therefore, the vascular changes may be a consequence of the structural changes induced by the raised blood pressure. 6. In established hypertension, no regression of vascular changes was observed despite prolonged reduction of blood pressure. The role of an increased vascular reactivity in the maintenance of hypertension is therefore questionable.

Animals↗
PubMed1972

Effects of dopamine on the conductance of perfused vascular beds of the chloralosed cat.

1. Dopamine produced vasoconstriction followed by secondary vasodilatation in the perfused cat hindquarters and splanchnic region. Low doses produced only vasodilatation in the splanchnic region.2. Phenoxybenzamine abolished, while despiramine and cocaine potentiated, the vasoconstrictor and secondary dilator actions of dopamine.3. After phenoxybenzamine, dopamine produced only vasodilatation in both the hindquarters and splanchnic region, being more effective in the latter.4. Haloperidol, but not propranolol, atropine or mepyramine, antagonized dopamine-induced vasodilatation.5. Dopamine differs from other catecholamines in that, while its cardiac effects are mediated by a beta-adrenoceptive mechanism, its vasodilator effects are not.6. The results support the concept of a specific receptor mediating dopamine vasodilatation.

Animals↗
PubMed1972

The effects of some phosphodiesterase inhibitors on the conductance of the perfused vascular beds of the chloralosed cat.

1. The vasoactivity of a number of phosphodiesterase inhibitors in the auto-perfused splanchnic region and hindquarters of the cat have been investigated.2. Theophylline, dipyridamole and 4-(3,4-dimethoxybenzyl)-2-imidazolidinone (Ro 7-2956) and its analogues were more potent vasodilators in the splanchnic region than in the hindquarters, whereas papaverine was a potent vasodilator in both these vascular beds.3. The vasodilator response to the phosphodiesterase inhibitors in the splanchnic region and hindquarters was not susceptible to beta-adrenoceptor blockade.4. Infusion of dibutyryl cyclic AMP into the superior mesenteric artery increased vascular conductance of the splanchnic region. This effect was enhanced by Ro 20-1724 in doses below those in which this compound affected conductance.5. These results are consistent with the hypothesis that accumulation of cyclic AMP in vascular smooth muscle mediates the vasodilator response to phosphodiesterase inhibitors.

Abdomen↗
PubMed1971

Modification of the vascular response to isoprenaline by cholinomimetic drugs.

1. Pilocarpine and other cholinomimetic drugs convert isoprenaline to a vasoconstrictor and pressor agent.2. This effect of pilocarpine was abolished by atropine; it is thus an acetylcholine-like response. It was not dependent on the integrity of the central nervous system or the adrenal glands and was not abolished by ganglionic blockade.3. The constrictor action of isoprenaline after pilocarpine was abolished by propranolol; this action of isoprenaline is thus on the beta-adrenoceptor. Another beta-adrenoceptor stimulating agent, salbutamol, resembled isoprenaline in this situation, though papaverine and acetylcholine did not.4. The constrictor action of isoprenaline after pilocarpine was abolished by phenoxybenzamine, guanethidine and cocaine; the effect did not appear after reserpine pretreatment.5. These results suggest an action of cholinomimetic drugs at adrenergic nerve endings which permits the uptake of beta-adrenoceptor stimulating agents resulting in the release of neuronal transmitter.

Acetylcholine↗
PubMedDate not supplied

Evidence for the involvement of alpha-adrenoceptor blockade in the antihypertensive action of diazoxide in the renal hypertensive rat.

The effects of diazoxide on the blood pressure and heart rate of conscious renal hypertensive rats have been investigated. The antihypertensive action of diazoxide has been studied in relation to the effects of diazoxide pretreatment on pressor responses to stimulation of the complete sympathetic outflow and to injections of noradrenaline, phenylephrine, angiotensin and serotonin in pithed rats. In pithed preparations, pressor responses to sympathetic nerve stimulation, and to injected noradrenaline and phenylephrine were significantly reduced by diazoxide pretreatment, at a time corresponding to maximal reduction of blood pressure in conscious animals. At this time there was no significant reduction of pressor responses to injected angiotensin or serotonin. These findings suggest a contribution of alpha-adrenoceptor blockade to the antihypertensive activity of diazoxide.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Ovarian cancer, Part I: Biology.

The ovary is among the more complex organs of the body and its functions are achieved by numerous cell types. All of these cell types have some tendency to undergo malignant transformation, but the vast majority of ovarian cancers are believed to be the result of malignant transformation of the ovarian surface epithelium. The concept that most ovarian cancer arises from this modified peritoneal mesothelium is credited to Sir Spencer Wells in 1872. Ovarian cancer is the most frequently fatal gynecologic malignancy, and approximately 20,000 cases per year are diagnosed in the United States. Progress in understanding the biology of this disease, including factors involved in its etiology, progression, and tendency to change from a relatively chemotherapy-sensitive tumor to one with marked drug resistance, has been slow. In this review, the complex features of the normal ovarian surface epithelial cells are considered in relation to the etiology and progression of the disease. The hypothesis that incessant or repetitious ovulation contributes to the initiation of the disease is explored in detail based on experimental data, epidemiologic information, and the potential for antioncogene inactivation in this interesting cell type. Lastly, based on the experimental data available, potential mechanisms of resistance to platinum, the cornerstone of aggressive ovarian cancer therapy, are discussed, as are approaches to overcoming drug resistance. It is hoped that the reader will be left with the feeling that the pace of our understanding of the biology of ovarian cancer is increasing at such a rate that answers to the questions of etiology and why chemotherapy often fails will be known in the foreseeable future.

Animals↗
PubMedDate not supplied

BRL 34915, a novel antihypertensive agent: comparison of effects on blood pressure and other haemodynamic parameters with those of nifedipine in animal models.

The effects of BRL 34915, (+/-) 6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl)-2H-b enzo [b]-pyran-3-ol, on blood pressure and other haemodynamic parameters in animals have been investigated in comparison with those of nifedipine. In conscious spontaneously hypertensive rats and renal hypertensive cats and dogs the oral doses of BRL 34915 lowering blood pressure are 10 to 30 times lower than those of nifedipine. Tachycardia evoked by BRL 34915 tends to be less than that produced by nifedipine in the cat and of similar magnitude in the dog. The antihypertensive response to BRL 34915 in these models is reproducible on repeat once daily dosing without rebound hypertension on cessation of dosing. In studies using electromagnetic flow probes to measure regional blood flow in anaesthetised cats the intravenous administration of BRL 34915, unlike that of nifedipine, markedly increases renal blood flow yet BRL 34915 lacks the marked effect of nifedipine on femoral blood flow. BRL 34915, a compound structurally unrelated to existing cardiovascular drugs, is a potent new antihypertensive agent having an interesting profile of activity that renders this compound of clinical interest.

Animals↗
PubMedDate not supplied

Translational research in ovarian cancer: a must.

Ovarian cancer discovered at late clinical stage continues to be a fatal disease. It seems self-evident that if we are to make an impact on the survival of advanced ovarian cancer patients, we must begin to understand the disease more completely. This should improve the diagnosis of the disease at an early stage when it is curable by surgery or develop better/targeted drug treatments. Modern molecular techniques have provided insights into many of the molecular changes that occur when ovarian cancer develops, but one must understand that changes seen in this way can only be said to correlate with disease. It would be helpful to have a way to test candidate changes for causality. In many cancer types, genetically engineered animals are beginning to be used for this purpose and as a means to study the disease process in greater detail. To date, there has been no way to study ovarian cancer by this means. Efforts to model human ovarian cancer have been delayed by a general lack of understanding both of the disease process in humans and of the cells widely believed to be the precursors of epithelial ovarian cancer, the ovarian surface epithelial (OSE) cells. Here, we present recent progress in modeling ovarian cancer using genetically modified mice.

Animals↗