Stimulation of nitric oxide synthesis and protective role of insulin in acute thrombosis in vivo

Asru K. Sinha, Sujoy Bhattacharya, Krishnendu Acharya, Sahana Mazumder

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Administration of physiologic amounts of insulin in mice (200 μunits/g body weight) resulted in 9 fold increase of basal nitric oxide level from 0.51±0.1224 nmol/ml (mean±SD, n=12) to 4.45±0.645 nmol/ml after 30min of the injection of the hormone. Since NO is a potent inhibitor of platelet aggregation both in vitro and in vivo, we tested the possibility whether the administration of the hormone would result in the in vivo inhibition of thrombosis through the increase of NO level in the circulation. It was found that administration of insulin (200 μunits/g body weight) in mice protected >90%(p<0.00001, n=500) of these animals from death due to thrombosis in the coronary arteries induced by ADP injection in the heart. This effect of insulin in vivo was found to be directly related to the hormone induced increase of NO level in the system. The thromboprotective effect of insulin could not be achieved by using either prostacyclin, a well known antithrombotic agent or its stable probe prostaglandin E1 instead of insulin. The efficacy of insulin was neither related to the blood glucose level nor was the consequence of the hypoglycemic effect of the hormone. In contrast, inhibition of insulin induced increase of NO level resulted in the complete loss of the thromboprotective effect of the hormone. These results suggest that insulin besides being a hypoglycemic hormone could also be a potent antithrombotic humoral factor.

Original languageEnglish (US)
Pages (from-to)2687-2696
Number of pages10
JournalLife Sciences
Volume65
Issue number25
DOIs
StatePublished - Nov 12 1999
Externally publishedYes

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Nitric Oxide
Thrombosis
Insulin
Hormones
Hypoglycemic Agents
Body Weight
Injections
Fibrinolytic Agents
Alprostadil
Platelet Aggregation Inhibitors
Epoprostenol
Adenosine Diphosphate
Blood Glucose
Coronary Vessels
Animals

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Stimulation of nitric oxide synthesis and protective role of insulin in acute thrombosis in vivo. / Sinha, Asru K.; Bhattacharya, Sujoy; Acharya, Krishnendu; Mazumder, Sahana.

In: Life Sciences, Vol. 65, No. 25, 12.11.1999, p. 2687-2696.

Research output: Contribution to journalArticle

Sinha, Asru K. ; Bhattacharya, Sujoy ; Acharya, Krishnendu ; Mazumder, Sahana. / Stimulation of nitric oxide synthesis and protective role of insulin in acute thrombosis in vivo. In: Life Sciences. 1999 ; Vol. 65, No. 25. pp. 2687-2696.
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