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 language | English |
|---|---|
| Pages (from-to) | 711-716 |
| Number of pages | 6 |
| Journal | Kidney International |
| Volume | 46 |
| Issue number | 3 |
| State | Published - Sep 1 1994 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Nephrology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Exogenous nitric oxide prevents endotoxin-induced glomerular thrombosis in rats
AU - Westberg, Gunnar
AU - Shultz, Pamela J.
AU - Raij, Leopoldo
PY - 1994/9/1
Y1 - 1994/9/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 7996792
AN - SCOPUS:0027930237
VL - 46
SP - 711
EP - 716
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 3
ER -