Tissue Distribution and Hypotensive Effect of Prazosin in the Conscious Rat

Dynon, M K; Jarrott, Bevyn; Louis, William J.

doi:10.1097/00005344-198303000-00012

Cited by 17 publications

(5 citation statements)

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“…The reduction of blood pressure in the presence of prazosin alone was not sustained throughout the experiment, in spite of the continued infusion of prazosin. It is not clear why this was so, but a similar time course of effects was previously observed following bolus prazosin administration to conscious rats (Dynon et al ., 1983). The effect cannot be explained by a reflex tachycardia, because of the absence of an increase in heart rate in the prazosin‐treated group above vehicle controls.…”

Section: Discussionsupporting

confidence: 65%

Complex adrenergic and inflammatory mechanisms contribute to phase 2 ventricular arrhythmias in anaesthetized rats

Clements‐Jewery

Andrag

Hearse

et al. 2009

British J Pharmacology

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Background and purpose: The mechanisms responsible for phase 2 (infarct-related) ventricular arrhythmias remain unclear. We have investigated the role of a1 and b1 adrenoceptor activation and the interaction of this with infarct neutrophil accumulation, in anaesthetized rats. Experimental approach: Neutrophil-replete Sprague-Dawley rats (n = 8-9 per group) were anaesthetized and randomized to receive vehicle, prazosin (0.5 mg·kg -1 i.v.), atenolol (4 mg·kg -1 i.v.) or their combination prior to left main coronary artery occlusion. A further group was depleted of neutrophils and received both atenolol and prazosin. Coronary ligation in all groups was maintained for 240 min. Key results: Atenolol and prazosin treatment lowered heart rates and blood pressures respectively, but neither agent given alone affected the incidence of phase 2 ventricular tachycardia or fibrillation. However, co-administration of atenolol with prazosin reduced phase 2 ventricular premature beats (log10-transformed totals were 1.25 Ϯ 0.26 vs. 2.43 Ϯ 0.18 in controls; P < 0.05). Neutrophil depletion attenuated this antiarrhythmic effect (log10-transformed total ventricular premature beats were 1.66 Ϯ 0.35; P > 0.05 vs. controls). Conclusions and implications:Phase 2 arrhythmias appear to depend in part on a complex interaction between catecholamines and neutrophils. A model of this interaction is proposed.

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Section: Discussionsupporting

confidence: 65%

Complex adrenergic and inflammatory mechanisms contribute to phase 2 ventricular arrhythmias in anaesthetized rats

Clements‐Jewery

Andrag

Hearse

et al. 2009

British J Pharmacology

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“…Therefore, it is conceivable that rABCG2 limits the brain penetration of its drug substrates by excreting them to the circulating blood. Indeed, the brain concentration of prazosin after intravenous administration was significantly lower than in other tissues (Dynon et al 1983). It has also been reported that the brain distribution of mitoxantrone is low (Stewart et al 1986).…”

Section: Discussionmentioning

confidence: 91%

Functional expression of rat ABCG2 on the luminal side of brain capillaries and its enhancement by astrocyte‐derived soluble factor(s)

Hori¹,

Ohtsuki²,

Tachikawa³

et al. 2004

Journal of Neurochemistry

127

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The purpose of the present study was to clarify the expression, transport properties and regulation of ATP-binding cassette G2 (ABCG2) transporter at the rat blood-brain barrier (BBB). The rat homologue of ABCG2 (rABCG2) was cloned from rat brain capillary fraction. In rABCG2-transfected HEK293 cells, rABCG2 was detected as a glycoprotein complex bridged by disulfide bonds, possibly a homodimer. The protein transported mitoxantrone and BODIPY-prazosin. In rat brain capillary fraction, rABCG2 protein was also detected as a glycosylated and disulfide-linked complex. Immunohistochemical analysis revealed that rABCG2 was localized mainly on the luminal side of rat brain capillaries, suggesting that rABCG2 is involved in brain-to-blood efflux transport. For the regulation study, conditionally immortalized rat brain capillary endothelial (TR-BBB13), astrocyte (TR-AST4) and pericyte (TR-PCT1) cell lines were used as an in vitro BBB model. Following treatment of TR-BBB13 cells with conditioned medium of TR-AST4 cells, the Ko143 (an ABCG2-specific inhibitor)-sensitive transport activity and rABCG2 mRNA level were significantly increased, whereas conditioned medium of TR-PCT1 cells had no effect. These results suggest that rat brain capillaries express functional rABCG2 protein and that the transport activity of the protein is up-regulated by astrocyte-derived soluble factor(s) concomitantly with the induction of rABCG2 mRNA. Keywords: ABCG2, astrocyte, blood-brain barrier, in vitro BBB model.

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“…Hydroxychloroquine treatment was also recently removed from the WHO Solidarity COVID-19 clinical study based on evidence from the Solidarity trial, a Cochrane review of the drug as well as on the release of a report from the UK-based RECOVERY trial where hydroxychloroquine showed no effect on mortality rate of COVID-19 patients [15,16]. Similarly, a post-exposure prophylaxis trial showed no effect of hydroxychloroquine on the incidence of infection from high and moderate-risk exposure to SARS-CoV-2 [17].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of drugs for Potential Repurposing against COVID-19 using a Tier-Based Scoring System

et al. 2019

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Tissue Distribution and Hypotensive Effect of Prazosin in the Conscious Rat

Cited by 17 publications

References 0 publications

Complex adrenergic and inflammatory mechanisms contribute to phase 2 ventricular arrhythmias in anaesthetized rats

Complex adrenergic and inflammatory mechanisms contribute to phase 2 ventricular arrhythmias in anaesthetized rats

Functional expression of rat ABCG2 on the luminal side of brain capillaries and its enhancement by astrocyte‐derived soluble factor(s)

Evaluation of drugs for Potential Repurposing against COVID-19 using a Tier-Based Scoring System

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