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J Appl Physiol 82: 1593-1600, 1997;
8750-7587/97 $5.00
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Journal of Applied Physiology
Vol. 82, No. 5, pp. 1593-1600, May 1997
SYSTEMIC CIRCULATION AND FLUID BALANCE

Nitric oxide-endothelin-1 interaction in humans

Gunvor Ahlborg and Jan M. Lundberg

Department of Clinical Physiology, Huddinge University Hospital, S-141 86 Huddinge; and Department of Physiology and Division of Pharmacology, Karolinska Institute, S-171 77 Stockholm, Sweden

Received 10 April 1996; accepted in final form 24 January 1997.

Ahlborg, Gunvor, and Jan M. Lundberg. Nitric oxide-endothelin-1 interaction in humans. J. Appl. Physiol. 82(5): 1593-1600, 1997.---Healthy men received NG-monomethyl-L-arginine (L-NMMA) intravenously to study cardiovascular and metabolic effects of nitric oxide synthase blockade and whether this alters the response to endothelin-1 (ET-1) infusion. Controls only received ET-1. L-NMMA effects were that heart rate (17%), cardiac output (17%), and splanchnic and renal blood flow (both 33%) fell promptly (all P < 0.01). Mean arterial blood pressure (6%), and systemic (28%) and pulmonary (40%) vascular resistances increased (P < 0.05 to 0.001). Arterial ET-1 levels (21%) increased due to a pulmonary net ET-1 release (P < 0.05 to 0.01). Splanchnic glucose output (SGO) fell (26%, P < 0.01). Arterial insulin and glucagon were unchanged. Subsequent ET-1 infusion caused no change in mean arterial pressure, heart rate, or cardiac output, as found in the present controls, or in splanchnic and renal blood flow or splanchnic glucose output as previously found with ET-1 infusion (G. Ahlborg, E. Weitzberg, and J. M. Lundberg. J. Appl. Physiol. 79: 141-145, 1995). In conclusion, L-NMMA like ET-1, induces prolonged cardiovascular effects and suppresses SGO. L-NMMA causes pulmonary ET-1 release and blocks responses to ET-1 infusion. The results indicate that nitric oxide inhibits ET-1 production and thereby interacts with ET-1 regarding increase in vascular tone and reduction of SGO in humans.

NG-monomethyl-L-arginine and endothelin-1 infusion; cardiac output; splanchnic and renal blood flow; systemic and pulmonary vascular resistance; arterial levels and pulmonary release of endothelin-1; insulin and splanchnic glucose output

0161-7567/97 $5.00 Copyright © 1997 the American Physiological Society




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