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Biomedical subjects

H G Dean

Publications and source records attributed to H G Dean.

31 records · Page 2Linked to original sources
PubMed1985

Plasma catecholamines during endotoxin infusion in conscious unrestrained rats: effects of adrenal demedullation and/or guanethidine treatment.

We have examined the effect of E coli endotoxin infusion (41 micrograms kg-1 min-1 iv for 4 h) on plasma concentrations of epinephrine (E), norepinephrine (NE), and dopamine (DA) in the conscious unrestrained rat. Saline infusion did not change catecholamine concentrations from the preinfusion values of 230.8 +/- 32.9 pg ml-1 (E), 456.8 +/- 104.9 pg ml-1 (NE), and 49.0 +/- 19.9 pg ml-1 (DA). Endotoxin produced marked elevations in all three catecholamines. At 1 h, the plasma concentrations were 3,279 +/- 494.6 pg ml-1 (E), 1,670 +/- 137.0 pg ml-1 (NE), and 191.5 +/- 13.7 pg ml-1 (DA). Thereafter, concentrations of E decreased whereas concentrations of NE and DA increased. These increases were prevented by a combination of adrenal demedullation (28 days previously) and treatment with guanethidine (25 mg kg-1 iv, -24 h) ("sympathectomy"). Guanethidine alone markedly reduced the peak NE concentrations without affecting the E concentrations or the 1-h NE concentrations. Demedullation alone prevented the increase in E and reduced the 1-h NE concentrations. Survival in such "sympathectomized" animals was markedly reduced (survival at 4 h in rats receiving endotoxin alone, 100%: in "sympathectomized" animals receiving endotoxin, 12.5%). The tachycardia produced by endotoxin was attenuated in "sympathectomized" rats and mean arterial blood pressure fell rapidly. Endotoxin-induced hyperglycemia was prevented by "sympathectomy" and hypoglycemia was evident as early as 1 h after commencing the infusion. Endotoxin produced hypoinsulinemia in normal rats but did not change plasma insulin values in "sympathectomized" animals, although these animals showed a pre-endotoxin fasting hyperinsulinemia. An important protective role for catecholamines is suggested, especially in the early stages of shock.

Adrenal Medulla↗
PubMed1984

Recurrence of asthma following removal of a noradrenaline-secreting phaeochromocytoma.

A patient with asthma and a phaeochromocytoma is described. At about the time she was first noted to be hypertensive her asthma resolved spontaneously but bronchospasm returned with some severity when the tumour was removed. The phaeochromocytoma was of the noradrenaline secreting variety. Possible mechanisms through which this catecholamine might have produced the observed alleviation of asthma are considered.

Adrenal Gland Neoplasms↗
PubMed1981

Whole brain tyrosine hydroxylase activity during the development of deoxycorticosterone acetate-1% sodium chloride-induced hypertension in rats.

Water was chosen as the optimal medium for the extraction of tyrosine hydroxylase (TH) from rat brain. Determination of TH activity in crude homogenates failed to exhibit a linear relationship between enzyme concentration and measured activity, however, when a supernatant was used, a linear relationship existed. At a time when TH activity is maximally increased in the locus coeruleus after reserpine treatment (Reis et al 1975; Zigmond.1979) (2.5 mg kg-1 day-1 for 3 days, kill 24 h after last dose) we could detect no alterations in whole brain TH, however if treatment continued for 4 days and animals were killed 72 h after the last dose it was possible to detect increases in TH activity in various brain regions. These results suggest that local changes in brain TH activity are not revealed in measurements made on whole brain. The early rise in blood pressure, following the administration of deoxycorticosterone acetate (doca) and 1% NaCl to male Wistar rats, was accompanied by bradycardia. Whole brain Th activity was determined in these hypertensive animals 6-21 days after the commencement of treatment and the results failed to confirm the reported elevation of TH activity (Rylett et al 1976). The results are discussed with reference to the TH assay employed.

Animals↗
PubMed1976

Brain tyrosine hydroxylase activity and systolic blood pressure in rats treated with either deoxycorticosterone and salt or angiotensin.

The hypertension induced in adult male rats by doca/salt was found to be accompanied by a significant rise in whole brain tyrosine hydroxylase (TH) activity. A smaller hypertensive effect, produced by angiotensin (750 ng kg-1 daily) was also accompanied by a proportional rise in whole brain TH activity. The specific antagonists spironolactone and saralasin completely blocked both responses in the doca/salt- and angiotensin-treated animals respectively and spironolactone showed a partial inhibition of the effects of angiotensin. In all the animals treated there was a clear correlation between systolic blood pressure and whole brain TH activity. The significance of these changes is discussed in the light of the central mechanism of hypertension.

Angiotensin II↗
PubMed1976

Absorption and excretion of 4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione (DA 2370) in man and dog.

The blood levels and excretion of radioactivity administered as 14C- or 3H-4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione (DA 2370) have been studied after oral administration to dogs and man. After a single dose of 14C- or 3H-DA 2370 (10 mg/kg) to dogs the daily loss of radioactivity in urine and faeces fell to less than 1% of the dose in 4 days and the plasma levels showed a biexponential decay with mean half-lives of 3.7 and 62 h. When a single 200 mg dose of 3H-DA 2370 was administered to human subjects maximum urinary excretion of radioactivity occurred during day 2 with 4% of the total during day 5. Maximum faecal excretion was on day 2-3 with 0.5% of the dose on day 7. The plasma half-life was 32.5 h. A similar dose three times a day for 3 days had a half-life of 39 h when dosing ceased; radioactivity in the urine and faeces was 2% and 2.5% of the dose, respectively, 4 days later.

Adult↗
PubMed1976

The distribution and excretion of 14C- and 3H-labelled 4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione (DA 2370) in the rat.

The distribution and excretion of radioactivity following a single or multiple oral administration of 3H-and/or 14C-4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione (DA 2370) has been determined in rats. The daily excretion of radioactivity following a single administration (3H and 14C) or multiple doses (3H) fell to less than 1% of the dose in 4 days. A similar fall was observed at the end of 10 days continuous administration. The radioactivity in plasma reached a maximum between 2 and 4 h after administration of the drug (14C). Tissue levels were found to be effectively zero 24 h after administration of the drug for up to 10 days. The very large amounts of radioactivity lost in bile were found to correlate with blood, tissue and faecal levels.

Administration, Oral↗
PubMedDate not supplied

Do alterations in prostanoid or catecholamine release influence the antiarrhythmic activity of nicergoline?

We examined the effects of nicergoline, an alpha-adrenoceptor blocking drug and an inhibitor of platelet phospholipase, on haemodynamics, blood gases, cardiac arrhythmias, and prostanoid and catecholamine release in anaesthetised greyhounds before, during, and after a 40-min occlusion of the left anterior descending coronary artery. Twenty-five minutes after commencing the intravenous infusion of nicergoline (50 micrograms kg-1 min-1) there were significant reductions in heart rate, arterial blood pressure, left ventricular dP/dtmax, and cardiac output. Nicergoline also increased the 0(2) extraction by the myocardium both before and during coronary artery occlusion. In contrast to control animals, heart rate decreased but there were no further reductions in arterial blood pressure during the occlusion period. Nicergoline improved survival (from 17 in control dogs to 50%) following the combined period of myocardial ischaemia and reperfusion and appeared to suppress the phase 1b occlusion-induced arrhythmias. The release of thromboxane B2 from the ischaemic myocardium was partially suppressed by nicergoline, and the ratio of 6-keto PGF1 alpha/thromboxane B2 (the stable breakdown products of prostacyclin and thromboxane A2, respectively) was increased. The washout of noradrenaline and adrenaline from the ischaemic myocardium following release of the occlusion was slightly enhanced by nicergoline. It is concluded that the beneficial metabolic and prostacyclin-promoting properties of nicergoline may be opposed by its action on noradrenaline washout, thus limiting its antiarrhythmic effectiveness.

6-Ketoprostaglandin F1 alpha↗