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Biomedical subjects

W R Dunn

Publications and source records attributed to W R Dunn.

At least 37 records · Page 2Linked to original sources
PubMed1991

The effects of nifedipine on alpha 2-adrenoceptor-mediated contractions in several isolated blood vessels from the rabbit.

1. The effects of the dihydropyridine calcium channel blocker, nifedipine, on noradrenaline-induced contractile responses have been examined in several isolated blood vessels from the rabbit, with particular emphasis on responses mediated via postjunctional alpha 2-adrenoceptors. 2. In the isolated renal vein, ear vein, distal saphenous artery, saphenous vein and plantaris vein, 0.1 microM and 1 microM nifedipine reduced responses elicited by 54 mM KCl by more than 70%. The remaining responses were abolished by alpha-adrenoceptor blockade, suggesting the involvement of noradrenaline released from neurones activating a dihydropyridine-resistant mechanism. 3. In the renal vein (alpha 1-), ear vein (predominantly alpha 2-), distal saphenous artery (alpha 1- greater than alpha 2-), saphenous vein and plantaris vein (alpha 2- greater than alpha 1-), 0.01 microM and 0.1 microM nifedipine produced concentration-related reductions in the maximum response to noradrenaline. However, 1 microM nifedipine was no more effective than 0.1 microM nifedipine and the reduction in the maximum varied from 10-25% of the control response. Thus, a sizeable component of the alpha-adrenoceptor-mediated response in all blood vessels is resistant to dihydropyridine calcium channel blockers and this appears to be unrelated to the alpha-adrenoceptor subtype involved. 4. Following irreversible inactivation of alpha 1-adrenoceptors and isolation of functional alpha 2-adrenoceptors in the saphenous vein, plantaris vein and distal saphenous artery (the latter requiring the presence of angiotensin II), the effect of nifedipine on responses to noradrenaline was increased. However, a component of the alpha 2-adrenoceptor response in each preparation was present even after the concentration of nifedipine was increased to 1 microM. 5. In the saphenous vein, a preparation in which it has been demonstrated previously that alpha 2-adrenoceptor-mediated responses are highly dependent upon the presence of extracellular calcium ions, partial depolarization with 20mM KCl failed to increase the inhibitory effect of 0.1 microM nifedipine. This suggests the involvement of dihydropyridine-resistant Ca2+ channels. The possible relationship between these dihydropyridine-resistant Ca2+ channels, alpha-adrenoceptor subtypes and 'receptor-operated' Ca2 + channels is discussed.

Animals↗
PubMed1991

Influence of angiotensin II on the alpha-adrenoceptors involved in mediating the response to sympathetic nerve stimulation in the rabbit isolated distal saphenous artery.

Under normal experimental conditions, sympathetic nerve-mediated responses to electrical field stimulation in the isolated distal saphenous artery of the rabbit are sensitive to prazosin (0.1 microM) and so, by definition, are mediated by alpha 1-adrenoceptors. In the presence of angiotensin II (A II, 0.05 microM) however, a component of the response to nerve stimulation became resistant to prazosin. This 'uncovered' response was virtually abolished by the selective alpha 2-adrenoceptor antagonist rauwolscine (1 microM), a concentration that in the absence of A II had enhanced nerve-mediated responses. Exposure to A II therefore, allows the clear demonstration of a role for postjunctional alpha 2-adrenoceptors in mediating the contractile response to sympathetic nerve stimulation in this arterial preparation.

Angiotensin II↗
PubMed1990

An examination of the sources of calcium for contractions mediated by postjunctional alpha 1- and alpha 2-adrenoceptors in several blood vessels isolated from the rabbit.

1. The roles of intracellular and extracellular-derived Ca2+ in alpha-adrenoceptor-mediated contractions to noradrenaline (NA) have been investigated in several isolated blood vessels from the rabbit by examining responses in the presence of a modified Krebs-Henseleit saline with 2.5 mM Ca2+ and a Ca2(+)-buffered saline with 0.1 microM free Ca2+. 2. NA was tested in preparations of the abdominal aorta, distal saphenous artery, renal vein, lateral saphenous vein, plantaris vein and ear vein exposed to a Ca2(+)-buffered saline with 0.1 microM [Ca2+]. A concentration of NA which was maximally effective in modified Krebs-Henseleit saline, produced an initial transient contraction (ITC) followed by a relaxation towards baseline. This is evidence that alpha-adrenoceptor-mediated responses in all these blood vessels depend upon calcium from both sources. 3. The ITC was particularly pronounced in the arteries and was associated more closely with the alpha 1-receptor subtype. In the abdominal aorta, distal saphenous artery and renal vein the ITC can almost exclusively be attributed to an alpha 1-adrenoceptor (prazosin-sensitive, rauwolscine-resistant). In the ear vein, and to a lesser extent the plantaris vein, the ITC was mediated in part by an alpha 2-adrenoceptor (prazosin-resistant, rauwolscine-sensitive). 4. alpha 2-Adrenoceptors in the lateral saphenous vein largely account for the response to NA in modified Krebs-Henseleit saline, but alpha 1-adrenoceptors mediate the ITC in Ca2(+)-buffered saline. After selective inactivation of alpha 1-adrenoceptors with a combination of phenoxybenzamine and rauwolscine, responses to NA in modified Krebs-Henseleit saline are slow in onset and there is no ITC in Ca2(+)-buffered saline. 5. The possible significance of the coupling of postjunctional alpha 2-adrenoceptors to dual sources of Ca2 + is discussed in relation to the interaction between alpha-adrenoceptor subtypes and the ease of demonstrating functional alpha 2-adrenoceptors in isolated blood vessels.

Animals↗
PubMed1990

Physiological modulation of alpha-adrenoceptor and 5HT receptor expression in blood vessels.

In vitro experiments on vascular smooth muscle often fail to reveal phenomena clearly demonstrable in vivo. Several recent observations in our laboratory have revealed the facility to uncover responses mediated by receptors whose functional expression had remained hidden with the standard experimental conditions first employed: conversely manipulation of conditions can selectively hide a particular receptor's response. Examples include the uncovering of responses to: 5HT1 receptors by raised O2 tension (via cyclooxygenase products) in human umbilical vessels; alpha 2-adrenoceptors in rabbit saphenous artery by angiotensin II and alpha 2-adrenoceptors in perfused rat tail by elevating tone with vasopressin. The powerful synergism of agonists which cannot on their own cause contraction, can lead to inaccurate interpretations of agonist-antagonist interactions. Finally, the influence of tissue metabolism on receptor expression clearly illustrates the complex processes which must be involved in vivo.

Animals↗
PubMed1989

Expression of functional postjunctional alpha 2-adrenoceptors in rabbit isolated distal saphenous artery--a permissive role for angiotensin II?

In the rabbit isolated distal saphenous artery, the population of postjunctional adrenoceptors is of the alpha 1 variety under normal in vitro experimental conditions, based on the potency order of selective agonists and on the effects of the antagonists prazosin and rauwolscine against responses to UK-14304. Angiotensin II (A II, 0.05 microM) however, without affecting resting baseline tension, markedly enhanced responses to UK-14304, particularly at low concentrations. This previously unseen component of the response to UK-14304 was resistant to prazosin (0.1 microM) but susceptible to rauwolscine (1 microM). A II would therefore appear to have a permissive role for the expression of a quiescent population of postjunctional alpha 2-adrenoceptors in the rabbit distal saphenous artery.

Adrenergic alpha-Agonists↗
PubMed1988

An attempt at selective protection from phenoxybenzamine of postjunctional alpha-adrenoceptor subtypes mediating contractions to noradrenaline in the rabbit isolated saphenous vein.

1. An attempt has been made, with the irreversible alpha-adrenoceptor antagonist phenoxybenzamine, to find the conditions under which postjunctional alpha 1-adrenoceptors in the rabbit isolated saphenous vein can be inactivated, such that postjunctional alpha 2-adrenoceptors can be studied in isolation. 2. Following exposure to various concentrations of phenoxybenzamine, no evidence was found for a selective inactivation of the postjunctional population of alpha 1-adrenoceptors: the "rauwolscine-resistant' (alpha 1-) and the "rauwolscine-sensitive' (alpha 2-) responses to (--)-noradrenaline were similarly affected. 3. However, in "receptor protection' experiments following exposure to a combination of phenoxybenzamine and the selective alpha 2-adrenoceptor antagonist rauwolscine, the remaining response to (--)-noradrenaline appeared to be mediated by a single population of postjunctional alpha 2-adrenoceptors: the response was insensitive to prazosin and rauwolscine was more potent than corynanthine. 4. Partial isolation of the alpha 1-adrenoceptor population was attempted by pre-exposure of the preparation to a combination of phenoxybenzamine and a selective alpha 1-adrenoceptor antagonist, i.e. prazosin or YM-12617. Following receptor protection, the inhibition produced by "selective' concentrations of either of these alpha 1-adrenoceptor antagonists were not significantly different from that observed in control preparations (no phenoxybenzamine). However, the selective alpha 2-adrenoceptor antagonists rauwolscine and CH-38083 were still able to inhibit part of the remaining responses to NA. This is interpreted as indicating that, in addition to protecting the putative postjunctional alpha 1-adrenoceptors, these procedures fail to produce complete inactivation of postjunctional alpha 2-adrenoceptors. 5. It is concluded that, although phenoxybenzamine appeared to be non-selective for the two populations of postjunctional alpha-adrenoceptors in the rabbit isolated saphenous vein, inclusion of a "selective' concentration of a competitive antagonist during the inactivation period results in differing degrees of functional protection of each subtype. Pharmacological isolation was possible for alpha 2-adrenoceptors but not convincingly for alpha 1-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1984

Educational strategies in curriculum development: the SPICES model.

Six education strategies have been identified relating to the curriculum in a medical school. Each issue can be represented as a spectrum or continuum: student-centred/teacher-centred, problem-based/information-gathering, integrated/discipline-based, community-based/hospital-based, elective/uniform and systematic/apprenticeship-based. The factors supporting a more towards each end of the continuum are presented for each strategy. Newer schools tend to be more to the left on the continuum, established schools more to the right. Each school, however, has to decide where it stands on each issue and to establish its own profile. This SPICES model of curriculum strategy analysis can be used in curriculum planning or review, in tackling problems relating to the curriculum and in providing guidance relating to teaching methods and assessment.

Clinical Clerkship↗
PubMed1982

Doctors who did not participate in a continuing education programme.

One hundred doctors were interviewed regarding their use of a series of educational programmes which had been mailed to them unsolicited. Doctors who used the materials did not differ from those who did not with respect to geographical location, sex and higher qualifications. The forty-five doctors who had used the programmes tended to be younger than those who did not. The commonest reason given for non-participation in the programme was lack of time. Following the interviews at least five doctors, who had not previously done so, used the programmes.

Age Factors↗
PubMed1979

Doctors accept a challenge: self-assessment exercises in continuing medical education.

A new approach to continuing medical education by distance learning has been implemented. A series of six patient-management problems or challenges were posted to 20 000 doctors throughout Britain. Each doctor had to decide on the diagnosis, investigations, and treatment of the patients described. The challenges covered problems that were important in the doctor's day-to-day work and were designed so that he could obtain immediate feedback about his decisions and compare his own responses with those of a specialist and those of his colleagues. Additional information was available by telephone and by post on request. The series has been well received and is being widely used.

Attitude of Health Personnel↗
PubMed1978

Attitudes of medical undergraduates in Glasgow to computer-assisted learning.

Computer-assisted learning (CAL) has been introduced as part of the undergraduate teaching course in general practice during the penultimate year of the medical course. The student is given an opportunity to make clinical decisions and to manage a case over a significant time scale. The attitudes of the students are favourable to this method of instruction.

Attitude of Health Personnel↗