Effect of inhibition of nitric oxide synthase on the vasopressor response to ephedrine.
Ephedrine is a mixed adrenergic agonist, stimulating both alpha- and beta-adrenergic receptors. The effects of ephedrine use include increases in heart rate, cardiac output, peripheral resistance, and blood pressure, and its use is associated with serious cardiovascular events such as stroke, arrhythmias, and myocardial infarction. The vascular endothelium plays a fundamental role in the regulation of vascular tone by releasing vasoactive factors such as nitric oxide (NO). The loss of NO bioactivity, often referred to as endothelial dysfunction, is characterized by the loss of endothelium-dependent vasodilation and is thought to be a common pathway for cardiovascular events such as vasospasm, hypertension, and myocardial infarction. Since endothelial dysfunction is characterized by loss of NO activity, and since ephedrine and endothelial dysfunction may be associated with similar cardiovascular events, the current study was undertaken to determine the effect of inhibition of NO production on responses to ephedrine in the rat. A sodium nitroprusside (SNP) infusion procedure was used to restore baseline vascular parameters to pre-L-NAME levels, allowing for direct comparison of agonist responses before and after NOS inhibition. The results demonstrate that the vascular response to ephedrine in the rat is modulated by NO and that NO production in response to ephedrine may be secondary to beta 2-receptor stimulation.
Dabisch
Paul A
PA
Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Liles
John T
JT
Kadowitz
Philip J
PJ
D000322:Adrenergic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004347:Drug Interactions; D004809:Ephedrine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D011433:Propranolol; D019001:Nitric Oxide Synthase; D004809:Ephedrine; D019331:NG-Nitroarginine Methyl Ester; D010646:Phentolamine