Atorvastatin prevents vascular hyporeactivity to norepinephrine in sepsis: Role of nitric oxide and α1-adrenoceptor mRNA Expression

Kathirvel Kandasamy, Shahid Prawez, Soumen Choudhury, Amar Sunil More, Azad Ahmed Ahanger, Thakur Uttam Singh, Subhashree Parida, Santosh Kumar Mishra

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Hyporeactivity to vasoconstrictors is one of the clinical manifestations of sepsis in man and experimental animals. The objective of the investigation was to examine whether atorvastatin can prevent hyporeactivity to norepinephrine (NE) in mouse aorta in sepsis, and if so, what are the mechanisms involved. Sepsis in mice was induced by cecal ligation and puncture. The aorta was harvested for tension experiment, nitric oxide (NO) and cyclic guanosine monophosphate measurements, and inducible NO synthase (iNOS) and α1D-adrenoceptor mRNA expression studies. In comparison with sham-operated controls, sepsis significantly decreased the contractile response to NE in the mouse aorta. Pretreatment with atorvastatin of septic animals completely restored NE-induced contractions to levels similar to those of sham-operated controls and significantly increased survival time and mean arterial pressure. Atorvastatin also attenuated iNOS-induced overproduction of NO, as well as iNOS mRNA expression. Accordingly, hyporeactivity to NE was not evident in tissues pretreated with selective iNOS inhibitor 1400W in sepsis. Although basal cyclic guanosine monophosphate accumulation in the aorta was reduced in sepsis, pretreatment of the tissues with soluble guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ) partially restored the reactivity to NE. Interestingly, hyporeactivity to NE in sepsis was associated with a decreased α1D-adrenoceptor mRNA expression in the mouse aorta. Atorvastatin pretreatment, however, prevented the decrease in α1D-adrenoceptor mRNA expression in septic animals. In conclusion, atorvastatin seems to prevent hyporeactivity to vasoconstrictor NE in the aorta from septic mice through attenuation of overproduction of NO as well as improved α1D-adrenoceptor mRNA expression. The findings of the present study may explain the beneficial effects of atorvastatin on improved hemodynamic functions in sepsis.

Original languageEnglish (US)
Pages (from-to)76-82
Number of pages7
JournalShock
Volume36
Issue number1
DOIs
StatePublished - Jul 2011
Externally publishedYes

Fingerprint

Adrenergic Receptors
Blood Vessels
Sepsis
Norepinephrine
Nitric Oxide
Aorta
Messenger RNA
Nitric Oxide Synthase
Cyclic GMP
Vasoconstrictor Agents
Atorvastatin Calcium
Nitric Oxide Synthase Type II
Punctures
Ligation
Arterial Pressure
Hemodynamics
Survival

Keywords

  • cecal ligation and puncture
  • hyporeactivity
  • nitric oxideα -adrenoceptor
  • Norepinephrine

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Kandasamy, K., Prawez, S., Choudhury, S., More, A. S., Ahanger, A. A., Singh, T. U., ... Mishra, S. K. (2011). Atorvastatin prevents vascular hyporeactivity to norepinephrine in sepsis: Role of nitric oxide and α1-adrenoceptor mRNA Expression. Shock, 36(1), 76-82. https://doi.org/10.1097/SHK.0b013e31821a4002

Atorvastatin prevents vascular hyporeactivity to norepinephrine in sepsis : Role of nitric oxide and α1-adrenoceptor mRNA Expression. / Kandasamy, Kathirvel; Prawez, Shahid; Choudhury, Soumen; More, Amar Sunil; Ahanger, Azad Ahmed; Singh, Thakur Uttam; Parida, Subhashree; Mishra, Santosh Kumar.

In: Shock, Vol. 36, No. 1, 07.2011, p. 76-82.

Research output: Contribution to journalArticle

Kandasamy, K, Prawez, S, Choudhury, S, More, AS, Ahanger, AA, Singh, TU, Parida, S & Mishra, SK 2011, 'Atorvastatin prevents vascular hyporeactivity to norepinephrine in sepsis: Role of nitric oxide and α1-adrenoceptor mRNA Expression', Shock, vol. 36, no. 1, pp. 76-82. https://doi.org/10.1097/SHK.0b013e31821a4002
Kandasamy, Kathirvel ; Prawez, Shahid ; Choudhury, Soumen ; More, Amar Sunil ; Ahanger, Azad Ahmed ; Singh, Thakur Uttam ; Parida, Subhashree ; Mishra, Santosh Kumar. / Atorvastatin prevents vascular hyporeactivity to norepinephrine in sepsis : Role of nitric oxide and α1-adrenoceptor mRNA Expression. In: Shock. 2011 ; Vol. 36, No. 1. pp. 76-82.
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