Biomedical subjects

B Jarrott

Publications and source records attributed to B Jarrott.

203 records · Page 12Linked to original sources

PubMedDate not supplied

Tissue distribution and hypotensive effect of prazosin in the conscious rat.

We investigated the hypotensive effect and tissue distribution of prazosin (1 mg/kg i.v.) in conscious rats. This dose caused an immediate fall in blood pressure, associated with a nonsignificant increase in heart rate. Blood pressure then gradually rose to control over a 2-h period. Prazosin was measured in plasma and tissue samples by high-pressure liquid chromatography. Highest concentrations of drug were found in liver and kidney and the lowest in brain. The rate of decline of prazosin from plasma was similar to its decline from the tissues, indicating a rapid equilibrium. This rate of disappearance was also similar to the decay of the hypotensive response and suggests that prazosin in plasma may be in equilibrium with prazosin at its site of action.

Animals↗

PubMedDate not supplied

Effects of blockade of extraneuronal uptake on responses to isoprenaline in perfused rat heart.

1. Isolated rat hearts accumulated 102 pmol/g wet wt/min of isoprenaline when perfused for 5 min with 0-6 muM (+/-)-3H-isoprenaline. 2. The 3-methoxy derivative of isoprenaline ('methoxy isoprenaline') (10 muM) significantly inhibited this uptake by 57%, metanephrine (10 muM) by 29% and normetanephrine (10 muM) by 21%. 3. (+/-)-Isoprenaline (0-6 muM) infused into isolated perfused rat hearts for 5 min activated glycogen phosphorylase 2-4-fold. Normetanephrine (10 muM) or metanephrine (10 muM included in the perfusate significantly potentiated this activation, but 3-0-methyl isoprenaline (10 muM significantly reduced it. However, 3-0-methyl isoprenaline potentiated the ability of 4-8 muM isoprenaline to stimulate phosphorylase. 4. Neither metanephrine (10 muM) nor normetanephrine (10 muM) altered peak inotropic responses to injections of (+/-)-isoprenaline into the solution perfusing isolated rat hearts. 3-0-methyl isoprenaline (10 muM) shifted the isoprenaline dose-response curve to the right, but did not affect the inotropic responses to CaCl2, confirming that 3-0-methyl isoprenaline possess beta-adrenoceptor antagonist activity. 5. Inotropic responses to isoprenaline were significantly prolonged by both 3-0-methyl isoprenaline and normetanephrine (10 muM). 6. These results indicate that blockade of extraneuronal accumulation of catecholamines causes potentiation of both metabolic and mechanical beta-adrenoceptor-mediated responses of the heart to isoprenaline. It is suggested that Uptake2 and the cardiac beta-adrenoceptor are separate entities, and that the beta-adrenoceptor is localized in the sarcolemma. The physiological function of Uptake2 may be to help clear the sympathetic synaptic gap of liberated neurotransmitter.

Animals↗

PubMedDate not supplied

Haemodynamic effects of a single low dose of prazosin in patients with chronic congestive cardiac failure correlations with pharmacokinetics.

The haemodynamic effects and pharmacokinetics of a single orally administered dose of 0.5 mg of prazosin have been compared in six patients with stable severe congestive cardiac failure. Administration of prazosin induced significant decreases in mean pulmonary capillary wedge pressure (from 27.5, s.e.m. = 4.5 to 19.4, s.e.m. = 5.1 mmHg; P less than 0.001), mean arterial blood pressure (from 94.5, s.e.m. = 6.0 to 85.4, s.e.m. = 5.0 mmHg; P less than 0.01), and systemic vascular resistance (from 1690, s.e.m. = 360 to 1420, s.e.m. = 200 dyn. s/cm5; P less than 0.05) and a rise in cardiac index from 1.98 (s.e.m. = 0.07) to 2.28 (s.e.m. = 0.16) litres/min per m2 (P less than 0.05). There was a non-significant fall in heart rate. Pharmacokinetic analysis revealed maximum plasma prazosin concentrations of 4.1 (s.e.m. = 1.4) ng/ml, occurring 2.1 (s.e.m. = 0.4) h after drug ingestion. The mean elimination half-life was 5.1 (s.e.m. = 0.8) h, which is longer than that found in our previous studies in normal subjects. There was considerable interindividual variation in peak plasma prazosin concentrations, elimination half-life and area under the concentration-time curve. While mean maximal haemodynamic effects of prazosin occurred at similar times to the peak plasma concentration of the drug, there was no significant correlation between the extent of haemodynamic response and individual pharmacokinetic parameters. It is concluded that significant and potentially beneficial haemodynamic effects occur with the initial administration of 0.5 mg oral dose of prazosin in patients with stable congestive cardiac failure and it is suggested that in many patients little advantage will be achieved with higher initial doses.

Aged↗

PubMedDate not supplied

Effects of methyldopa metabolites on amine transmitters and adrenergic receptors in rat brain.

Studies of catecholamine concentrations in defined nuclei from the anterior hypothalamic-preoptic regions and the medulla oblongata, known to contribute to cardiovascular control, were measured following acute or chronic methyldopa administration. These studies indicated that methyldopa was enzymatically converted to methyldopamine and methylnorepinephrine, and in some areas to methylepinephrine which replaced endogenous epinephrine. The predominant metabolite was methylnorepinephrine, which accumulated in concentrations higher than endogenous norepinephrine levels. (-)Methylnorepinephrine was found to be 6 times more potent and 75 times more selective for alpha 2-adrenergic receptors than (-) norepinephrine, and it is suggested that this alpha 2-adrenergic receptor action, particularly in the nucleus tractus solitarius, contributes to a major part of the antihypertensive effect of methyldopa.

Animals↗

PubMedDate not supplied

Pharmacokinetics of prazosin in normotensive subjects after low oral doses.

A method for measuring plasma prazosin concentrations is reported. This method, which involves high pressure liquid chromatography (HPLC) combined with fluorescence detection, has a sensitivity 20 times that of previous conventional fluorimetric techniques and twice that of other HPLC methods, and can be used to study the pharmacokinetics of prazosin at very low doses. Plasma prazosin concentrations were measured in 5 normal volunteers for 24 hours after single oral doses of 0.5 and 1.5mg of prazosin. On average, the lag time was 0.650 and 0.448 hours, and the elimination half-life 2.3 and 2.5 hours, for the 0.5 and 1.5mg doses, respectively. Peak prazosin concentrations occurred between 1.1 and 3.6 hours after dosing, and after the 1.5mg doses were associated with symptoms of faintness.

Adult↗