Exogenous nitric oxide prevents endotoxin-induced glomerular thrombosis in rats

Gunnar Westberg, Pamela J. Shultz, Leopoldo Raij

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Nitric oxide (NO) synthesized from L-arginine is an endogenous vasodilator and inhibitor of platelet adhesion and aggregation. Gram-negative lipopolysaccharide (LPS) can induce NO synthesis, which may mediate the pathophysiologic effects of endotoxemia. In addition, our previous studies suggested that LPS-induced NO may protect against thrombosis in rats. In the present study, male Sprague-Dawley rats given LPS (0.1 mg/kg) i.p. increased their urinary excretion of NO2 + NO3 (stable end-products of NO) by 4.3-fold. Rats given 10 μg/kg/hr i.v. of nitroglycerin (GTN), an exogenous NO donor, showed a similar increase. L-NAME, an inhibitor of NO synthesis, abrogated the increase in urinary NO2 + NO3 in LPS-treated rats but not in rats given GTN. Glomerular thrombosis developed in rats given LPS + L-NAME (thrombosis score = 3.02 ± 0.4), while those given LPS + L-NAME + GTN were largely protected (thrombosis score = 1.37 ± 0.5, P < 0.05). Atrial natriuretic peptide (ANP), an NO-independent vasodilator, neither increased urinary NO2 + NO3 nor prevented glomerular thrombosis (thrombosis score = 2.68 + 0.5, NS). Hydralazine, another vasodilator without effects on NO or platelets, also failed to prevent glomerular thrombosis in rats given LPS + L-NAME. We conclude that in endotoxemia, the antithrombogenic properties of endogenously synthesized NO are important in preventing alomerular thrombosis. The exogenously NO donor, GTN, can substitute for the antithrombogenic effect of endogenous NO. Clinically, administration of NO synthesis inhibitors to treat endotoxic shock may need to be combined with concomitant administration of exogenous NO donors to prevent microvascular thrombosis.

Original languageEnglish
Pages (from-to)711-716
Number of pages6
JournalKidney International
Volume46
Issue number3
StatePublished - Sep 1 1994
Externally publishedYes

Fingerprint

Endotoxins
Nitric Oxide
Thrombosis
Lipopolysaccharides
NG-Nitroarginine Methyl Ester
Nitric Oxide Donors
Vasodilator Agents
Endotoxemia
Hydralazine
Platelet Aggregation Inhibitors
Nitroglycerin
Atrial Natriuretic Factor
Septic Shock
Sprague Dawley Rats
Arginine
Blood Platelets

ASJC Scopus subject areas

  • Nephrology

Cite this

Westberg, G., Shultz, P. J., & Raij, L. (1994). Exogenous nitric oxide prevents endotoxin-induced glomerular thrombosis in rats. Kidney International, 46(3), 711-716.

Exogenous nitric oxide prevents endotoxin-induced glomerular thrombosis in rats. / Westberg, Gunnar; Shultz, Pamela J.; Raij, Leopoldo.

In: Kidney International, Vol. 46, No. 3, 01.09.1994, p. 711-716.

Research output: Contribution to journalArticle

Westberg, G, Shultz, PJ & Raij, L 1994, 'Exogenous nitric oxide prevents endotoxin-induced glomerular thrombosis in rats', Kidney International, vol. 46, no. 3, pp. 711-716.
Westberg, Gunnar ; Shultz, Pamela J. ; Raij, Leopoldo. / Exogenous nitric oxide prevents endotoxin-induced glomerular thrombosis in rats. In: Kidney International. 1994 ; Vol. 46, No. 3. pp. 711-716.
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