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Updated: Jun 29, 2026

Preparation of Rat Skeletal Muscle Homogenates for Nitrate and Nitrite Measurements
Published on: July 29, 2021
[Inhibition of nitric oxide synthesis during bacterial shock does not prevent development of resistant hypotension
Abstract:
The study subject was the white rat-males Wistar after intra-peritoneal injection of the mixture of St. aureus and B. pyocyaneus daily cultures in the dose calculated as 1 milliard microbial organisms of each species per 100 g b.w., as well as the vascular preparations isolated from aortas of those rats. The aim is to study nitric oxide role in the development of resistant hypotension under generalization of the purulent infection. Infection of the animals with a mixture of gram-positive and gram-negative cultures led to the development of the pathological process, which can be considered as a septic (bacterial) shock. A primary lowering of the vascular tone caused by depression of the myocardial pump and contractile functions was observed. Injection of methylene blue or NOS blockers (L-NAME, S-methyl-thiourea) to the infected animals in the moment of hypotension development caused only a short-term rise in blood pressure. Survival rate in such animals was significantly lower compared to the control infected animals. Repeated injections of those agents hastened death of the experimental animals. The experiments in vitro revealed no dilatory effect of acetylcholine with preserved sensitivity of the vascular preparations to adrenomimetics and exogenous nitric oxide in both control infected animals and animals injected with methylene blue or NOS blockers. The data obtained suggested that resistant hypertension in terminal stages of septic shock is nitric oxide-independent.
Insights
This study investigated nitric oxide's role in septic shock-induced hypotension in rats. Results indicate that resistant hypotension in severe sepsis is independent of nitric oxide signaling pathways.
Area of Science:
- Microbiology
- Pathophysiology
- Pharmacology
Background:
- Sepsis, a severe infection, can lead to septic shock with resistant hypotension.
- The role of nitric oxide (NO) in the vascular dysfunction of septic shock remains incompletely understood.
Purpose of the Study:
- To investigate the involvement of nitric oxide in the development of resistant hypotension during generalized purulent infection in a rat model.
- To determine the efficacy of nitric oxide synthase (NOS) inhibition in mitigating hypotension and improving survival during septic shock.
Main Methods:
- Wistar rats were infected with a mixture of Staphylococcus aureus and Pseudomonas aeruginosa.
- Vascular preparations from rat aortas were used for in vitro studies.
- Nitric oxide synthase inhibitors (L-NAME, S-methyl-thiourea) and methylene blue were administered during hypotension.
Main Results:
- Infection induced a septic shock-like state with hypotension and reduced vascular tone.
- Administration of NOS blockers or methylene blue resulted in only transient blood pressure increases and decreased survival rates.
- In vitro experiments showed no acetylcholine-induced vasodilation in infected or treated vessels, despite preserved sensitivity to other agents.
Conclusions:
- Resistant hypotension in the terminal stages of septic shock is nitric oxide-independent.
- Interference with nitric oxide pathways does not improve outcomes and may worsen survival in this septic shock model.
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