Circulatory consequences of reduced endogenous nitric oxide production during small-volume resuscitation

G. Molnár, E. Csonka, A. Vass, M. Borós, J. Kaszaki

Research output: Contribution to journalArticle

Abstract

Hypertonic small-volume resuscitation transiently restores the cardiovascular function during various circulatory disturbances. Nitric oxide (NO) is an important mediator of flow-induced peripheral and central hemodynamic changes, and therefore, we hypothesized that a decreased endogenous NO production could influence the consequences and the effectiveness of hypertonic fluid therapy. The main goal of this study was to outline and compare the circulatory effects small volume hypertonic saline-dextran (HSD, 7.5% NaCl-10% dextran; 4 ml/kg iv) infusion with (n=7) or without (n=7) artificially diminished NO production in normovolemic anesthetized dogs. HSD administration significantly increased cardiac index (CI), coronary flow (CF) and myocardial contractility, and elevated plasma nitrite/nitrate (NO x) and endothelin-1 (ET-1) levels. However, the late (2 h) postinfusion period was characterized by significantly decreased myocardial NO synthase (NOS) and enhanced myeloperoxidase activities. Pre-treatment with the non-selective NOS inhibitor N-nitro-L-arginine (NNA, 4 mg/kg) immediately increased cardiac contractility, and the HSD-induced CI and CF elevations and the positive inotropy were absent. Additionally, plasma ET-1 levels increased and NO x levels were significantly decreased. In conclusion, our results demonstrate that HSD infusion leads to preponderant vasoconstriction when endogenous NO synthesis is diminished, and this could explain the loss of effectiveness of HSD resuscitation in NO-deficient states.

Original languageEnglish
Pages (from-to)393-408
Number of pages16
JournalActa Physiologica Hungarica
Volume98
Issue number4
DOIs
Publication statusPublished - Dec 1 2011

Fingerprint

Resuscitation
Nitric Oxide
Endothelin-1
Nitric Oxide Synthase
dextran - saline drug combination
Fluid Therapy
Nitrites
Dextrans
Vasoconstriction
Nitrates
Peroxidase
Arginine
Hemodynamics
Dogs

Keywords

  • cardiac contractility
  • endothelin-1
  • hypertonic saline-dextran
  • nitric oxide

ASJC Scopus subject areas

  • Physiology (medical)

Cite this

Circulatory consequences of reduced endogenous nitric oxide production during small-volume resuscitation. / Molnár, G.; Csonka, E.; Vass, A.; Borós, M.; Kaszaki, J.

In: Acta Physiologica Hungarica, Vol. 98, No. 4, 01.12.2011, p. 393-408.

Research output: Contribution to journalArticle

@article{ffdda2221cea46b6b0ca2e97a042833b,
title = "Circulatory consequences of reduced endogenous nitric oxide production during small-volume resuscitation",
abstract = "Hypertonic small-volume resuscitation transiently restores the cardiovascular function during various circulatory disturbances. Nitric oxide (NO) is an important mediator of flow-induced peripheral and central hemodynamic changes, and therefore, we hypothesized that a decreased endogenous NO production could influence the consequences and the effectiveness of hypertonic fluid therapy. The main goal of this study was to outline and compare the circulatory effects small volume hypertonic saline-dextran (HSD, 7.5{\%} NaCl-10{\%} dextran; 4 ml/kg iv) infusion with (n=7) or without (n=7) artificially diminished NO production in normovolemic anesthetized dogs. HSD administration significantly increased cardiac index (CI), coronary flow (CF) and myocardial contractility, and elevated plasma nitrite/nitrate (NO x) and endothelin-1 (ET-1) levels. However, the late (2 h) postinfusion period was characterized by significantly decreased myocardial NO synthase (NOS) and enhanced myeloperoxidase activities. Pre-treatment with the non-selective NOS inhibitor N-nitro-L-arginine (NNA, 4 mg/kg) immediately increased cardiac contractility, and the HSD-induced CI and CF elevations and the positive inotropy were absent. Additionally, plasma ET-1 levels increased and NO x levels were significantly decreased. In conclusion, our results demonstrate that HSD infusion leads to preponderant vasoconstriction when endogenous NO synthesis is diminished, and this could explain the loss of effectiveness of HSD resuscitation in NO-deficient states.",
keywords = "cardiac contractility, endothelin-1, hypertonic saline-dextran, nitric oxide",
author = "G. Moln{\'a}r and E. Csonka and A. Vass and M. Bor{\'o}s and J. Kaszaki",
year = "2011",
month = "12",
day = "1",
doi = "10.1556/APhysiol.98.2011.4.3",
language = "English",
volume = "98",
pages = "393--408",
journal = "Physiology International",
issn = "2498-602X",
publisher = "Akademiai Kiado",
number = "4",

}

TY - JOUR

T1 - Circulatory consequences of reduced endogenous nitric oxide production during small-volume resuscitation

AU - Molnár, G.

AU - Csonka, E.

AU - Vass, A.

AU - Borós, M.

AU - Kaszaki, J.

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Hypertonic small-volume resuscitation transiently restores the cardiovascular function during various circulatory disturbances. Nitric oxide (NO) is an important mediator of flow-induced peripheral and central hemodynamic changes, and therefore, we hypothesized that a decreased endogenous NO production could influence the consequences and the effectiveness of hypertonic fluid therapy. The main goal of this study was to outline and compare the circulatory effects small volume hypertonic saline-dextran (HSD, 7.5% NaCl-10% dextran; 4 ml/kg iv) infusion with (n=7) or without (n=7) artificially diminished NO production in normovolemic anesthetized dogs. HSD administration significantly increased cardiac index (CI), coronary flow (CF) and myocardial contractility, and elevated plasma nitrite/nitrate (NO x) and endothelin-1 (ET-1) levels. However, the late (2 h) postinfusion period was characterized by significantly decreased myocardial NO synthase (NOS) and enhanced myeloperoxidase activities. Pre-treatment with the non-selective NOS inhibitor N-nitro-L-arginine (NNA, 4 mg/kg) immediately increased cardiac contractility, and the HSD-induced CI and CF elevations and the positive inotropy were absent. Additionally, plasma ET-1 levels increased and NO x levels were significantly decreased. In conclusion, our results demonstrate that HSD infusion leads to preponderant vasoconstriction when endogenous NO synthesis is diminished, and this could explain the loss of effectiveness of HSD resuscitation in NO-deficient states.

AB - Hypertonic small-volume resuscitation transiently restores the cardiovascular function during various circulatory disturbances. Nitric oxide (NO) is an important mediator of flow-induced peripheral and central hemodynamic changes, and therefore, we hypothesized that a decreased endogenous NO production could influence the consequences and the effectiveness of hypertonic fluid therapy. The main goal of this study was to outline and compare the circulatory effects small volume hypertonic saline-dextran (HSD, 7.5% NaCl-10% dextran; 4 ml/kg iv) infusion with (n=7) or without (n=7) artificially diminished NO production in normovolemic anesthetized dogs. HSD administration significantly increased cardiac index (CI), coronary flow (CF) and myocardial contractility, and elevated plasma nitrite/nitrate (NO x) and endothelin-1 (ET-1) levels. However, the late (2 h) postinfusion period was characterized by significantly decreased myocardial NO synthase (NOS) and enhanced myeloperoxidase activities. Pre-treatment with the non-selective NOS inhibitor N-nitro-L-arginine (NNA, 4 mg/kg) immediately increased cardiac contractility, and the HSD-induced CI and CF elevations and the positive inotropy were absent. Additionally, plasma ET-1 levels increased and NO x levels were significantly decreased. In conclusion, our results demonstrate that HSD infusion leads to preponderant vasoconstriction when endogenous NO synthesis is diminished, and this could explain the loss of effectiveness of HSD resuscitation in NO-deficient states.

KW - cardiac contractility

KW - endothelin-1

KW - hypertonic saline-dextran

KW - nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=84255189446&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84255189446&partnerID=8YFLogxK

U2 - 10.1556/APhysiol.98.2011.4.3

DO - 10.1556/APhysiol.98.2011.4.3

M3 - Article

C2 - 22173021

AN - SCOPUS:84255189446

VL - 98

SP - 393

EP - 408

JO - Physiology International

JF - Physiology International

SN - 2498-602X

IS - 4

ER -