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Biomedical subjects

D B Frewin

Publications and source records attributed to D B Frewin.

144 records · Page 8Linked to original sources
PubMed1970

The effect of ethyl alcohol and chlorpromazine on the response of the hand blood vessels to cold.

1. The response of hand blood flow to a measured cold stimulus was determined using venous occlusion plethysmography in normal subjects, before and after orally administered alcohol, and in patients on chlorpromazine therapy.2. The average resting hand blood flow of the patients taking chlorpromazine, as well as the constriction of these blood vessels to cold, was the same as in the normal subjects.3. Oral alcohol caused a rise in resting hand blood flow in the normal subjects and also modified the response of the hand blood vessels to cooling.4. A patient with a completely denervated hand was also studied. Oral alcohol did not increase the blood flow through the part, but it modified the hand vascular response to cold.5. These results suggest a diminished reactivity of the hand blood vessels to cold in the presence of alcohol.

Adult↗
PubMed1969

Modification of the vasoconstrictor action of sympathomimetic agents by bretylium tosylate and tranylcypromine in man.

1. The vasoconstrictor actions of tyramine, methylamphetamine and ephedrine on the blood vessels of the human hand have been found to be potentiated by administration intra-arterially of the adrenergic neurone blocking agent, bretylium tosylate.2. One mechanism suggested for the enhancement of vasoconstriction is that bretylium possesses monoamine oxidase inhibiting activity, which, in the case of tyramine, is protective both to the sympathomimetic agent and the intra-neuronal transmitter which it releases. In the case of methylamphetamine and ephedrine, which are not substrates for the enzyme, protection of the intra-neuronal transmitter alone might occur, accounting for the lesser degree of potentiation of the effect of these amines by bretylium.3. Comparison of the influences of bretylium and the monoamine oxidase inhibitor, tranylcypromine, on the vasoconstrictor action of the sympathomimetic agents shows a similar pattern of enhancement in the presence of both these drugs.4. Tranylcypromine caused enhancement of the response of the hand vessels to noradrenaline, and this action could contribute to its potentiation of the effect of the sympathomimetic amines.5. For a monoamine oxidase inhibiting action of bretylium to be effective in potentiating the constrictor actions of the sympathomimetic agents on the hand blood vessels at a time when reflex sympathetic activity is blocked it is necessary to postulate that these drugs and reflex nerve activity act either on different compartments of the transmitter store or by different release mechanisms.

Bretylium Compounds↗
PubMedDate not supplied

Histamine levels in stored human blood.

The histamine content in plasma samples obtained from a group of healthy blood donors, from blood stored in citrate-phosphate-dextrose supplemented with adenine (CPDA) packs for up 28 days, and from the side arm of a transfusion line was measured by radio-enzymatic assay. Healthy donors had a mean plasma histamine content of 0.79 ng per ml. Blood stored in CPDA initially showed a similar histamine level (0.69 ng/ml on day 3 of storage), but there was a progressive rise with time, and at 28 days, the level was 20.5 ng per ml. The increase in histamine is best described by a positive exponential and may be explained by a process whereby the plasma histamine level increases the degree of histamine release from blood cells. The histamine levels in the blood infused into patients tended to be higher than those found in the stored units of the same age, if these packs were less than 7 days old. This may have been caused by the unit becoming warmer during transfusion. We speculate that the histamine levels in the older units of stored blood were high enough to cause or augment transfusion reactions and that the storage age of blood may have a bearing on the incidence of transfusion reactions.

Blood Preservation↗
PubMedDate not supplied

A comparative study of antipyrine pharmacokinetics in saliva and plasma using a colourimetric method of antipyrine analysis.

1. Half-life, apparent volume of distribution and metabolic clearance rate for antipyrine elimination were reliably estimated from either plasma or saliva samples. 2. Pharmacokinetic analysis of antipyrine from saliva utilizing a simple and sensitive colourimetric technique provided a convenient method for assessing the activity of hepatic microsomal drug-metabolizing enzymes.

Adult↗
PubMedDate not supplied

The influence of the renin angiotensin system on abnormal expression of nerve growth factor in the spontaneously hypertensive rat.

1. The levels of the neurotrophic factor, nerve growth factor (NGF) in the mesenteric vascular bed of the spontaneously hypertensive rat (SHR) were greater than those in the corresponding vascular bed of normotensive Wistar-Kyoto rats (WKY). 2. Administration of angiotensin II (200 ng/kg per min, by minipump) for 2 weeks to juvenile WKY rats increased the levels of NGF in the mesenteric vasculature to those seen in untreated SHR. 3. Administration of the angiotensin II receptor antagonists losartan (30 mg/kg per day, p.o.) or PD144277 (10 mg/kg per day, p.o.) to juvenile SHR for 4 weeks reduced the levels of NGF such that they were indistinguishable from the values obtained for normotensive WKY rats. 4. The results confirm the elevated level of NGF in the mesenteric vasculature of the SHR and suggest that angiotensin II may play a role in regulating the abnormal concentrations of the protein in this tissue.

Angiotensin II↗
PubMedDate not supplied

5-Hydroxytryptamine-induced contraction of the marmoset aorta is mediated by a 5-HT1-like receptor.

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5-HT2 antagonist ketanserin. The aim of the present study was to define the receptors mediating the contractile activity of 5-HT in the marmoset aorta. 2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A2 agonist U44069 in order to amplify the responses; or (ii) exposed to N(omega)-nitro-L-arginine (100 micromol/L) plus LY 53857 (0.1 micromol/L; a 5-HT2 receptor antagonist shown previously to inhibit relaxation). The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was also investigated. 3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8-hydroxy-2-(di-n-propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT3 and 5-HT4 receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase. 4. The above effects fulfill the criteria for a 5-HT1-like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT1-like receptor.

Animals↗
PubMedDate not supplied

Responses to cholecystokinin octapeptide in patients with functional abdominal pain syndromes.

Clues to the pathogenesis of functional pain syndromes may be derived from the study of stimuli that precipitate or aggravate symptoms. In this study, cholecystokinin octapeptide (CCK-8, 0.06 microgram/kg) and placebo were given by intravenous infusion (5 min) in random order to control subjects and four groups of patients with unexplained abdominal pain. Induction of pain and nausea were assessed by linear analogue scales while sympathoadrenomedullary responses were assessed by serial changes in plasma concentrations of noradrenaline, adrenaline and dopamine. Scores for pain and nausea were low after infusion of placebo. After infusion of CCK-8, pain scores were significantly higher in patients with spontaneous pain than in control subjects, but significant increases in nausea were restricted to patients with irritable bowel syndrome and a subgroup of patients with pain after cholecystectomy. Although some groups showed increases in plasma concentrations of catecholamines after the infusion of CCK-8, the size of these increases was neither consistent among patients within each group nor predictive of scores of pain and nausea in individual subjects. Pain during the infusion of CCK-8 was a feature common to patients with diverse functional pain syndromes, and did not appear to be attributable to activation of the sympathetic nervous system.

Abdominal Pain↗
PubMedDate not supplied

Identification of a nonendothelial cell thromboxane-like constrictor response and its interaction with the renin-angiotensin system in the aorta of spontaneously hypertensive rats.

Aortic ring preparations from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were treated with N omega-nitro-L-arginine (NOLA, 10(-4) M). This produced a sustained contraction in preparations from SHR but not WKY rats. A similar contraction in aortic ring preparations from the SHR was produced with methylene blue (10(-5) M) and NG-monomethyl-L-arginine (10(-5) M). The NOLA-induced contraction was reversed with indomethacin (8 x 10(-6) M), ridogrel (10(-5) M) and SQ 29548 (10(-6) M) thus confirming the involvement of thromboxane A2/prostaglandin H2 processes. Subsequent experiments demonstrated that the thromboxane-like contraction was not dependent upon the presence of endothelial cells and occurred in preparations from young, prehypertensive (5 week) and older (17 week) SHRs. The thromboxane-like contraction was markedly suppressed with chronic captopril treatment and reinstated 4 weeks after withdrawal from captopril. The addition of saralasin (10(-6) M) or captopril (10(-6) M) to aortic ring preparations did not suppress the thromboxane-like contractions. The foregoing findings support the presence of a nonendothelial cell thromboxane-like constrictor agent in the aorta of the SHR that is revealed after impairment of nitric oxide production. The activity of the thromboxane-like constrictor process is not tightly linked to prevailing blood pressure, but is reduced with chronic in vivo inhibition of the angiotensin-converting enzyme.

Animals↗
PubMedDate not supplied

Functional tolerance to alpha-adrenergic receptor blockade in the spontaneously hypertensive rat highlights the multifunctional role of vascular angiotensin II in the development of hypertension.

Treatment of spontaneously hypertensive rats (SHR) with alpha-adrenoceptor antagonists failed to alter the development of hypertension in this animal model. However, agents such as captopril (CAP) and losartan (LOS) which interfere with the renin-angiotensin system effectively prevented the development of hypertension. When tolerance occurred in the presence of doxazosin (DOX) or phenoxybenzamine, there was an enhanced sensitivity to the blood pressure lowering influence of LOS. In the presence of CAP, at a dose that did not retard the development of blood pressure in the SHR, DOX treatment significantly offset the development of hypertension in this strain. These results suggest that a functional tolerance to agents that interfere with the sympathetic nervous system is mediated by the renin-angiotensin system. Angiotensin-converting enzyme inhibition was associated with a normalization of the enhanced contraction of the mesenteric vascular bed seen in preparations from the SHR and a suppression in the development of the vascular amplifier. The results suggest that the sympathetic nervous system is unable to maintain an elevated blood pressure in the SHR during interference with the functioning of the renin-angiotensin system. Conversely, under conditions of alpha-adrenoceptor blockade, angiotensin II can maintain an elevated blood pressure in the SHR.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Idiopathic orthostatic hypotension controlled with a monoamine oxidase inhibitor and 9-alpha-fluorohydrocortisone.

A case of orthostatic hypotension with autonomic failure is presented, and the patient's clinical response to the combined regime of a monoamine oxidase inhibitor and 9-alpha-fluorohydrocortisone is discussed. This therapy provided a relatively convenient means of alleviating the patient's symptoms and appears to be of considerable value in the management of orthostatic hypotension. However, close patient supervision is essential when these drugs are used as they cause hypertension in the supine position in subjects with poor baroreceptor function.

Blood Pressure↗