Nitric oxide-endothelin-1 interaction in humans.
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 resistance 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 (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.
Ahlborg
G
G
Department of Clinical Physiology, Huddinge University Hospital, Sweden.
Lundberg
J M
JM
D000328:Adult; D001784:Blood Gas Analysis; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D019332:Endothelin-1 / Q000097:blood*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005934:Glucagon / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000502:physiology; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D001786:Blood Glucose; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007328:Insulin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D005934:Glucagon; D019001:Nitric Oxide Synthase