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European Journal of Pharmacology Jan 2021This study examined the effect of linolenic acid on the contraction of isolated endothelium-intact and -denuded rat aorta induced by phenylephrine and its underlying...
This study examined the effect of linolenic acid on the contraction of isolated endothelium-intact and -denuded rat aorta induced by phenylephrine and its underlying mechanism. This was conducted in the presence or absence of N-nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), methylene blue, and calmidazolium. The effects of linolenic acid on contraction induced by calcium chloride in calcium-free Krebs solution containing 60 mM potassium chloride were also examined. Moreover, the effect of linolenic acid on the association between intracellular calcium level ([Ca]) and tension induced by phenylephrine was examined. Finally, we examined the effects of linolenic acid on cGMP formation and endothelial nitric oxide synthase (eNOS) phosphorylation induced by phenylephrine. Linolenic acid (5 × 10 M) increased phenylephrine-induced contraction in endothelium-intact aorta (standardized mean difference [SMD] of log ED: 2.23), whereas it decreased this contraction in endothelium-denuded aorta (SMD: 1.96). L-NAME, ODQ, methylene blue, and calmidazolium increased phenylephrine-induced contraction in endothelium-intact aorta. Linolenic acid decreased contraction induced by calcium chloride in calcium-free Krebs solution containing 60 mM potassium chloride in endothelium-denuded aorta. Linolenic acid caused an increase in [Ca] (SMD at 3 × 10 M phenylephrine: 1.63) and calcium sensitivity induced by phenylephrine in endothelium-intact aorta. Conversely, linolenic acid decreased [Ca] (SMD: 0.99) induced by phenylephrine in endothelium-denuded aorta. Linolenic acid decreased cGMP formation and eNOS phosphorylation induced by phenylephrine. These results suggest that linolenic acid increases phenylephrine-induced contraction, which is attributed to linolenic acid inhibition of endothelial NO release rather than its decrease of [Ca] in vascular smooth muscle.
Topics: Animals; Aorta; Dose-Response Relationship, Drug; Drug Synergism; Human Umbilical Vein Endothelial Cells; Humans; Male; Organ Culture Techniques; Phenylephrine; Rats; Rats, Sprague-Dawley; Vasoconstriction; alpha-Linolenic Acid
PubMed: 33131719
DOI: 10.1016/j.ejphar.2020.173662 -
American Journal of Veterinary Research Nov 2023To elucidate the cardiovascular effects of escalating doses of phenylephrine and norepinephrine in dogs receiving acepromazine and isoflurane.
OBJECTIVE
To elucidate the cardiovascular effects of escalating doses of phenylephrine and norepinephrine in dogs receiving acepromazine and isoflurane.
ANIMALS
8 beagles aged 1 to 2 years (7.4 to 11.2 kg).
METHODS
All dogs received acepromazine 0.01 mg/kg, propofol 4 to 5 mg/kg, and isoflurane and were mechanically ventilated. Mean arterial pressure (MAP) from a femoral artery catheter and continuous electrocardiogram were recorded. Cardiac output (CO) was measured with transpulmonary thermodilution. Systemic vascular resistance (SVR), global end-diastolic volume (GEDV), and global ejection fraction (GEF) were subsequently calculated. Phenylephrine and norepinephrine were infused in random order at 0.07, 0.3, 0.7, and 1.0 μg/kg/min. All variables were measured after 15 minutes of each infusion rate. The effects of dose, agent, and their interaction on the change of each variable were evaluated with mixed-effect models. A P < .05 was used for significance.
RESULTS
Atrial premature complexes occurred in 3 dogs during norepinephrine infusion at doses of 0.3, 0.7, and 1 μg/kg/min; no dysrhythmias were seen with phenylephrine administration. MAP increased during dose escalation (P < .0001) within each agent and did not differ between agents (P = .6). The decrease in HR was greater for phenylephrine (P < .0001). Phenylephrine decreased CO and GEF and increased GEDV and SVR (all P < .03). Norepinephrine decreased the SVR and increased CO, GEDV, and GEF (all P < .03).
CLINICAL RELEVANCE
Our results confirm that phenylephrine increases arterial pressures mainly through vasoconstriction in acepromazine-premedicated dogs while norepinephrine, historically considered a vasopressor, does so primarily through an increase in inotropism.
Topics: Animals; Dogs; Acepromazine; Isoflurane; Norepinephrine; Phenylephrine; Blood Pressure
PubMed: 37657733
DOI: 10.2460/ajvr.23.06.0147 -
Investigative Ophthalmology & Visual... Oct 2021Phenylephrine has been shown to affect intraocular pressure (IOP) but the mechanism of action is poorly understood. However, its action as a vasoconstrictor suggests...
PURPOSE
Phenylephrine has been shown to affect intraocular pressure (IOP) but the mechanism of action is poorly understood. However, its action as a vasoconstrictor suggests possible effects on episcleral venous pressure (EVP). In this study, we evaluated the effect of phenylephrine on EVP and IOP in healthy subjects.
METHODS
Forty eyes of 20 subjects were included. Each subject received 3 drops of phenylephrine 2.5% in one eye at 1-minute intervals. The fellow eye served as control. Blood pressure, heart rate, and IOP and EVP of both eyes were measured at baseline, 15 minutes, and 60 minutes after instillation of phenylephrine. IOP was measured by pneumatonometry. EVP was assessed by using a computer-controlled episcleral venomanometer. Changes in IOP, EVP, blood pressure, and heart rate at 15 and 60 minutes were analyzed by paired t-tests.
RESULTS
IOP increased 15 minutes after instillation of phenylephrine in both treated (P = 0.001) and control eyes (P = 0.01) and returned to baseline at 60 minutes. The change in IOP at 15 minutes was not significantly different between the 2 groups. EVP in treated eyes was unchanged at 15 minutes (P = 0.8) but decreased significantly at 60 minutes (P < 0.001). In control eyes, there was no change in EVP at any time (P > 0.6). There were no significant changes from baseline in systolic and diastolic blood pressure and heart rate after instillation of phenylephrine.
CONCLUSIONS
IOP elevation associated with topical phenylephrine is not caused by an increase in EVP in healthy subjects. Instead, EVP decreases with phenylephrine, but the mechanism remains to be determined.
Topics: Administration, Topical; Adrenergic alpha-1 Receptor Agonists; Adult; Dose-Response Relationship, Drug; Female; Healthy Volunteers; Humans; Intraocular Pressure; Male; Middle Aged; Phenylephrine; Sclera; Venous Pressure; Young Adult
PubMed: 34617960
DOI: 10.1167/iovs.62.13.4 -
Journal of Clinical Monitoring and... Jun 2019
Topics: Animal Experimentation; Animals; Hemodynamics; Phenylephrine; Stroke Volume; Veins
PubMed: 30478524
DOI: 10.1007/s10877-018-0225-1 -
Anesthesia and Analgesia Oct 2021Intraoperative hypotension is a common event, and a recent study suggests that maintenance of blood pressure may reduce complications. The splanchnic circulation...
BACKGROUND
Intraoperative hypotension is a common event, and a recent study suggests that maintenance of blood pressure may reduce complications. The splanchnic circulation provides a reservoir of blood that can be mobilized during hemorrhage; hence, intestinal microcirculation is sensitive to volume changes. The aim of this study was to assess the impact of hemorrhage on intestinal microcirculation and hemodynamics, and the effects of phenylephrine on these parameters.
METHODS
Eight anesthetized, mechanically ventilated Yorkshire/Landrace crossbreed pigs were studied. Graded hemorrhage was performed with the removal of 20% of blood volume in 5% increments. Hemodynamic and intestinal microcirculatory measurements were performed at each stage with side-stream dark field microscopy, following which mean arterial pressure (MAP) was corrected with phenylephrine to baseline values and measurements repeated. A repeated measurement 1-way analysis of variance (ANOVA) was used to compared changes from baseline measurements.
RESULTS
The mean baseline microcirculation score was 42 (standard deviation [SD] = 5). A 5% hemorrhage decreased the microcirculation score by a mean difference of 19 (95% confidence interval [CI], 12-27; P < .0001), and an additional 5% hemorrhage further reduced the microcirculation score by a mean difference of 12 (95% CI, 4-19; P = .0001). Subsequent hemorrhage or administration of phenylephrine did not significantly change the microcirculation scores except when phenylephrine was administered at the 15% hemorrhage stage, which increased the microcirculation score by a mean difference of 7 (95% CI, 1-13; P = .003). All hemodynamic variables were returned to baseline values following hemorrhage by the phenylephrine infusion.
CONCLUSIONS
Intestinal microcirculatory flow is reduced early in hemorrhage and is uncorrected by phenylephrine infusion. Hemodynamic changes associated with hemorrhage are corrected by phenylephrine and do not reflect microcirculatory flow status.
Topics: Animals; Disease Models, Animal; Female; Hemodynamics; Hemorrhage; Intestines; Microcirculation; Phenylephrine; Splanchnic Circulation; Sus scrofa; Time Factors; Vasoconstrictor Agents
PubMed: 33755645
DOI: 10.1213/ANE.0000000000005388 -
PloS One 2019Optical coherence tomography angiography (OCT-A) enables visualization of retinal microcirculation. As a potential influence of mydriatic eye drops on retinal vessel... (Clinical Trial)
Clinical Trial
PURPOSE
Optical coherence tomography angiography (OCT-A) enables visualization of retinal microcirculation. As a potential influence of mydriatic eye drops on retinal vessel density (VD) was proposed, the purpose of the present study was to investigate an influence of 5% phenylephrine and 0.5% tropicamide on macula and peripapillary VD.
METHODS
30 eyes of 30 healthy persons were measured by en face OCT-A (Spectralis OCT II, Heidelberg Engineering, Heidelberg). Scans of the macula (12 sectors, region of interest, ROI: 6.10 mm2) and peripapillary region (4 sectors, ROI: 2.67 mm2) were performed before (-) and 30 minutes after application of phenylephrine 5% and tropicamide 0.5% (+) eye drops (scan size was 8.41 mm2). Macula microcirculation was quantified in 3 retinal layers (superficial vascular plexus (SVP), deep capillary plexus (DCP), intermediate capillary plexus (ICP)). Data analysis was performed with the Erlangen-Angio-Tool.
RESULTS
(I) Mean VD was 33.03±2.3 (SVP), 23.53±2.9 (ICP) and 25.48±4.2 (DCP) before and 33.12±2.4 (SVP), 23.74±2.9 (ICP) and 25.82±4.0 (DCP) with mydriasis respectively. (II) Sectorial analysis: 30.63±2.9-34.45±2.9 (-) and 31.04±2.9-34.34±2.7 (+) in SVP; 22.61±2.9-24.93±3.2 (-) and 22.75±2.5-25.20±3.0 (+) in ICP; 24.56±4.7-26.45±3.4 (-) and 25.00±4.1-27.07±3.5 (+) in DCP. (III) Peripapillary region showed a mean VD of 31.82±3.8 before and 31.59±4.3 after mydriasis. Sectorial analysis of VD yielded a range of 31.04±4.1-32.65±3.8 (-) and 30.98±4.4-31.89±4.1 (+). (IV) Macula and peripapillary VD were not different before and after mydriasis (p>0.05).
CONCLUSION
Pharmacologic mydriasis did not influence retinal microcirculation in macula and peripapillary region enabling OCT-A scans with enhanced imaging process and scan quality.
Topics: Adult; Angiography; Female; Humans; Macula Lutea; Male; Microvessels; Middle Aged; Phenylephrine; Prospective Studies; Retinal Vessels; Tomography, Optical Coherence; Tropicamide
PubMed: 31622357
DOI: 10.1371/journal.pone.0221395 -
Journal of the American Heart... Sep 2023Background Pathological cardiac hypertrophy is a major cause of heart failure morbidity. The complex mechanism of intermolecular interactions underlying the pathogenesis...
Background Pathological cardiac hypertrophy is a major cause of heart failure morbidity. The complex mechanism of intermolecular interactions underlying the pathogenesis of cardiac hypertrophy has led to a lack of development and application of therapeutic methods. Methods and Results Our study provides the first evidence that TRAF4, a member of the tumor necrosis factor receptor-associated factor (TRAF) family, acts as a promoter of cardiac hypertrophy. Here, Western blotting assays demonstrated that TRAF4 is upregulated in cardiac hypertrophy. Additionally, TRAF4 deletion inhibits the development of cardiac hypertrophy in a mouse model after transverse aortic constriction surgery, whereas its overexpression promotes phenylephrine stimulation-induced cardiomyocyte hypertrophy in primary neonatal rat cardiomyocytes. Mechanistically, RNA-seq analysis revealed that TRAF4 promoted the activation of the protein kinase B pathway during cardiac hypertrophy. Moreover, we found that inhibition of protein kinase B phosphorylation rescued the aggravated cardiomyocyte hypertrophic phenotypes caused by TRAF4 overexpression in phenylephrine-treated neonatal rat cardiomyocytes, suggesting that TRAF4 may regulate cardiac hypertrophy in a protein kinase B-dependent manner. Conclusions Our results revealed the regulatory function of TRAF4 in cardiac hypertrophy, which may provide new insights into developing therapeutic and preventive targets for this disease.
Topics: Mice; Animals; Rats; Proto-Oncogene Proteins c-akt; TNF Receptor-Associated Factor 4; Heart Failure; Phenylephrine; Cardiomegaly
PubMed: 37642020
DOI: 10.1161/JAHA.122.028185 -
European Journal of Anaesthesiology May 2017
Topics: Anesthesia, Spinal; Blood Pressure; Cardiac Output; Humans; Phenylephrine
PubMed: 28375980
DOI: 10.1097/EJA.0000000000000609 -
Veterinary Ophthalmology Nov 2021Evaluate the effect of repeated doses of topical 1% cyclopentolate hydrochloride alone and in combination with topical 2.5% phenylephrine on pupil diameter (PD), tear...
OBJECTIVE
Evaluate the effect of repeated doses of topical 1% cyclopentolate hydrochloride alone and in combination with topical 2.5% phenylephrine on pupil diameter (PD), tear production (STT-1), intraocular pressure (IOP), digestive function (gut motility and feces production), and heart rate (HR).
ANIMAL STUDIED
Six healthy mares.
PROCEDURES
In a prospective, randomized, controlled, and crossover design study, the left eye of six healthy mares was administered 0.2 mL of cyclopentolate alone and in combination with 0.2 mL of phenylephrine. The drugs were administered 3 times a day for 1 day, twice a day for 1 day, and then once a day for 2 days, as commonly used in practice. Daily and two days after the last topical drug administration, HR, digestive auscultation, feces production, STT-1, IOP, and PD were recorded.
RESULTS
The cyclopentolate alone significantly increased the horizontal and vertical PD of the treated eye from day 2 to day 6 (p < .0001) compared with the baseline value. The combination with topical phenylephrine did not have any additional effect on mydriasis compare with the cyclopentolate alone. The other ocular and digestive parameters were not affected by repeated doses of cyclopentolate alone or combined.
CONCLUSIONS
Repeated administration of cyclopentolate alone or combined with phenylephrine induce a significant mydriasis for at least 48 h after the last administration in normal horses' eyes, and do not affect STT-1, IOP, digestive function, and HR. The phenylephrine combined with the cyclopentolate did not potentiate the pupil dilation when compared with cyclopentolate alone in healthy horses.
Topics: Administration, Topical; Animals; Cyclopentolate; Female; Horses; Mydriatics; Ophthalmic Solutions; Phenylephrine; Prospective Studies; Pupil
PubMed: 33982406
DOI: 10.1111/vop.12896 -
American Journal of Health-system... May 2018Results of an evaluation of the physical and chemical stability of extemporaneously prepared adult and pediatric ophthalmic solutions containing combinations of...
PURPOSE
Results of an evaluation of the physical and chemical stability of extemporaneously prepared adult and pediatric ophthalmic solutions containing combinations of phenylephrine, tropicamide, and cyclopentolate are reported.
METHODS
A stability study was conducted to help determine the feasibility of innovative formulations to meet an unmet clinical need for combination mydriatic ophthalmic eyedrops. An adult mydriatic ophthalmic solution containing phenylephrine hydrochloride 2.5% and tropicamide 1.0% and a pediatric formulation containing phenylephrine hydrochloride 2.5%, tropicamide 0.5%, and cyclopentolate hydrochloride 0.5% were prepared using proper aseptic techniques. Triplicate samples of each formulation were stored for 60 days at refrigeration temperatures (2-8 °C) and analyzed on day 0 and days 7, 14, 28, and 60. At each time point, the stability samples were assessed by visual inspection, pH measurement, and stability-indicating high-performance liquid chromatography (HPLC) analysis.
RESULTS
Over the 60-day storage period, there was no significant change in the visual appearance or pH level of any of the adult or pediatric solution samples. The results of HPLC analysis indicated that all samples retained 97-102% of the initial drug concentrations for up to 60 days.
CONCLUSION
Both adult and pediatric ophthalmic formulations containing combinations of phenylephrine, tropicamide, and cyclopentolate were stable physically and chemically for up to 60 days when stored at refrigeration temperatures (2-8 °C).
Topics: Adult; Chemistry, Pharmaceutical; Child; Chromatography, High Pressure Liquid; Cyclopentolate; Drug Combinations; Drug Compounding; Drug Stability; Drug Storage; Humans; Hydrogen-Ion Concentration; Mydriatics; Ophthalmic Solutions; Phenylephrine; Refrigeration; Time Factors; Tropicamide
PubMed: 29691266
DOI: 10.2146/ajhp161068