Correspondence

Effect of L-Arginine on Plasminogen-Activator Inhibitor in Hypertensive Patients with Hypercholesterolemia

N Engl J Med 1993; 328:287-288January 28, 1993

Article

To the Editor:

Vascular endothelium converts L-arginine to nitric oxide. An increase in blood pressure after the inhibition of nitric oxide synthase suggests that a deficiency of nitric oxide may contribute to the pathogenesis of hypertension1. Indeed, exogenous L-arginine produces systemic hypotension in patients with essential hypertension2.

Sodium nitroprusside (a nitric oxide donor) inhibits the release of plasminogen-activator inhibitor (PAI) from platelets and has fibrinolytic properties3. Plasma PAI activity is increased in patients with hypertension, venous thrombosis, and recurrent myocardial infarction4.

L-Arginine hydrochloride (Boehringer-Mannheim), at a daily dose of 60 mmol given over a three-hour period, was infused for seven consecutive days into the cubital veins of five men (38 to 64 years of age) admitted to our clinic because of obliterating atherosclerosis of the lower limbs (stage II according to Fontaine). The patients gave their consent, and the local ethics committee approved the study. Two of the patients had hypertension (blood pressure, 160/90 and 190/90 mm Hg) and hypercholesterolemia (cholesterol level, 8.7 and 8.8 mmol per liter); plasma levels of PAI were elevated (19 and 26 U per milliliter). The blood pressure and plasma cholesterol levels of the three remaining patients were not elevated, and the mean plasma level of PAI was 11 U per milliliter. Blood pressure was measured in the contralateral arm every 15 minutes. Plasma PAI levels were measured in citrated (3.8 percent) venous blood with a chromogenic PAI assay kit (Spectrolyse, Biopool). The plasma PAI levels were determined before and immediately after each infusion.

In the three patients without hypertension and hypercholesterolemia, infusions of L-arginine produced only insignificant effects on PAI, plasma cholesterol, and blood pressure. In the two patients with hypertension and hypercholesterolemia, however, L-arginine lowered plasma PAI levels to 9 and 15 U per milliliter. This effect was observed at the end of each infusion and waned within 12 hours. Moreover, in these two patients, the infusions of L-arginine lowered plasma cholesterol levels to 6.5 and 6.7 mmol per liter, and blood pressure dropped to 130/80 mm Hg in both patients. Thus, the infusion of L-arginine was associated with a decrease in plasma PAI and cholesterol levels as well as normalization of blood pressure in the two hypertensive patients with hypercholesterolemia but not in the other three patients. We surmise that these effects are associated with the conversion of L-arginine to endothelium-derived relaxing factor (nitric oxide). Our assumption is supported by the finding that in the two hypertensive patients with hypercholesterolemia, L-arginine caused an increase in the plasma levels of cyclic guanosine monophosphate from 4.8 to 9.6 pmol per milliliter, whereas it had no such effect in the two other patients in whom it was measured. Plasma levels of cyclic guanosine monophosphate may be used as an indicator of the stimulation of soluble guanylate cyclase by endothelium-derived relaxing factor (nitric oxide)5.

Richard Korbut, Ph.D.
Krzysztof Bieron, M.D.
Richard J. Gryglewski, M.D., D.Sc.
Nicolaus Copernicus University School of Medicine, 31-531 Krakow, Poland

5 References

1. 1

   Moncada S, Higgs EA, Hodson HF, et al. The L-arginine:nitric oxide pathway. J Cardiovasc Pharmacol 1991;17:Suppl 3:S1-S9
   CrossRef | Web of Science

2. 2

   Nakaki T, Hishikawa K, Suzuki H, Saruta T, Kato R. L-arginine-induced hypotension. Lancet 1990;336:696-696
   CrossRef | Web of Science | Medline

3. 3

   Lidbury PS, Korbut R, Vane JR. Sodium nitroprusside modulates the fibrinolytic system in the rabbit. Br J Pharmacol 1990;101:527-530
   Web of Science | Medline

4. 4

   Hamsten A, de Faire U, Walldius G, et al. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987;2:3-9
   CrossRef | Web of Science | Medline

5. 5

   Burton GA, MacNeil S, de-Jonge A, Haylor J. Cyclic GMP release and vasodilatation induced by EDRF and atrial natriuretic factor in the isolated perfused kidney of the rat. Br J Pharmacol 1990;99:364-368
   Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Nick Calvino. (2003) Connective tissue: Vascular and hematological (blood) support. Journal of Chiropractic Medicine 2:1, 25-36
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2. 2

   Ryszard J. Gryglewski. (1995) Interactions Between Endothelial Mediators. Pharmacology & Toxicology 77:1, 1-9
   CrossRef

3. 3

   R. J. GRYGLEWSKI, S. CHŁOPICKI, J. ŚWIĘLS, P. NIEZABITOWSKI. (1994) Prostacyclin, Nitric Oxide, and Atherosclerosisa. Annals of the New York Academy of Sciences 748:1, 194-206
   CrossRef