Objective: Hyperdynamic circulation and systemic vasodilation complicate cirrhosis of the liver and are related to vasoconstrictor hyporeactivity. We investigated whether impaired vasoconstrictor responsiveness may be overcome by antioxidants in patients with decompensated alcoholic cirrhosis.
Design: Controlled clinical study.
Setting: University setting.
Patients: Nine patients with liver cirrhosis Child-Pugh grade C and nine healthy age-matched volunteers.
Interventions: Forearm blood flow responses to intra-arterial norepinephrine, angiotensin II, and the nitric oxide synthase inhibitor N-monomethyl-l-arginine were measured by strain-gauge plethysmography and compared between groups of patients. To assess the role of oxidative stress, the antioxidant vitamin C (24 mg/min) was administered locally into the brachial artery, and forearm blood flow responses were reassessed.
Measurements And Main Results: Plasma concentrations of vitamin C were lower in patients with cirrhosis (p < .05). In patients with cirrhosis, the reactivity to norepinephrine and angiotensin II was markedly reduced (p < .05 vs. controls). Coadministration of vitamin C completely restored the potency of vasoconstrictors to that in controls but had no effect in healthy subjects. No changes were observed in time-control experiments in cirrhosis patients (n = 3) employing vehicle coinfusion. The response to N-monomethyl-L-arginine was comparable between groups and not affected by vitamin C.
Conclusions: Oxidative stress with consumption of antioxidants seems to play an important role in the development of vasoconstrictor hyporeactivity in patients with cirrhosis. Antioxidant therapy may be a promising clinical approach to restore vasoconstrictor hyporeactivity in these patients.
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http://dx.doi.org/10.1097/01.ccm.0000178173.27923.eb | DOI Listing |
Eur J Pharmacol
November 2024
Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Brazil. Electronic address:
Background: Phosphodiesterase-4 (PDE4) is responsible for terminating cyclic adenosine monophosphate (cAMP) signalling. PDE4 inhibitors, such as roflumilast (RFM), have anti-inflammatory activity and have been studied in inflammation-induced tissue damage in sepsis. However, the role of RFM on cardiovascular derangements induced by sepsis is still unknown.
View Article and Find Full Text PDFMicrocirculation
August 2024
The Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Lab of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China.
Shock is characterized with vascular hyporesponsiveness to vasoconstrictors, thereby to cause refractory hypotension, insufficient tissue perfusion, and multiple organ dysfunction. The vascular hyporeactivity persisted even though norepinephrine and fluid resuscitation were administrated, it is of critical importance to find new potential target. Ion channels are crucial in the regulation of cell membrane potential and affect vasoconstriction and vasodilation.
View Article and Find Full Text PDFShock
January 2024
Department of Dentistry, Universidade Estadual de Ponta Grossa, Ponta Grossa, Brazil.
Cecal ligation and puncture (CLP) is the gold standard model for studying septic shock, which is characterized by hypotension and hyporeactivity to vasoconstrictors. However, approximately 30% of CLP animals do not exhibit cardiovascular changes, requiring more replicates because of the high variability of the model. Therefore, biomarkers enabling the early prediction of cardiovascular collapse in sepsis would greatly benefit sepsis nonclinical studies, refining experimental models and improving clinical translation.
View Article and Find Full Text PDFJ Recept Signal Transduct Res
December 2023
Smooth Muscle Pharmacology & Molecular Pharmacology Laboratory, Department of Veterinary Pharmacology & Toxicology, College of Veterinary Science and Animal Husbandry, Uttar Pradesh Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go-Anusandhan Sansthan (DUVASU), Mathura, India.
Purpose: Hyporeactivity to vasopressors leading to multiple organ failure is a serious clinical implication in sepsis. Though the regulatory role of purinoceptors in inflammation is reported, their involvement in sepsis-induced vasoplegia is still unknown. Thus we investigated the effect of sepsis on vascular AT1 and PY receptors.
View Article and Find Full Text PDFNitric Oxide
May 2023
Departamento de Ciências Fisiológicas, Universidade Estadual de Londrina - UEL, Londrina, PR, Brazil. Electronic address:
Introduction: Available studies have shown the involvement of nitric oxide (NO) in the processes that lead to neurodegeneration in Parkinson's disease (PD). Also, the use of inhibitors of the inducible isoform of NO-synthase (iNOS) promotes neuroprotection and attenuates dopamine (DA) loss in experimental models of Parkinsonism. In addition, NO also appears to be involved in cardiovascular changes in 6-hydroxydopamine (6-OHDA)-induced Parkinsonism.
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