Early endotoxic shock results in enhanced vasodilator responses to nitroglycerin but unaltered responses to neuropeptides calcitonin gene-related peptide and substance P.
To determine the role that vasoactive neuropeptides, calcitonin gene-related peptide, and substance P play in tissue-blood flow regulation during early septic shock, we examined the responsiveness of arteries removed from pigs 3 h after administration of Escherichia coli lipopolysaccharide or saline vehicle. The carotid, cranial mesenteric, and left anterior descending coronary arteries were excised, and rings were cut from each vessel. Constrictor responses were obtained to cumulative doses of norepinephrine or potassium chloride. Rings were reconstricted and challenged with acetylcholine, substance P, calcitonin gene-related peptide, and nitroglycerin. Lipopolysaccharide significantly increased the cranial mesenteric artery's response to high concentrations of norepinephrine and the response to nitroglycerin in all vessels. This enhancement of responses to nitroglycerin suggests augmented smooth-muscle responsiveness to an exogenous source of nitric oxide, possibly associated with early depression of basal endothelial function. Depression of agonist-induced nitric oxide release may mask such enhancement with endothelial-dependent dilators and may enhance the response to adrenergic constrictors in some vascular beds.
Arden
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Department of Surgery, University of Kentucky College of Medicine, Lexington 40536, USA.
Fiscus
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Wang
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Maley
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Lanzo
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Gross
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D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004926:Escherichia coli / Q000472:pathogenicity; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D005996:Nitroglycerin / Q000494:pharmacology*; D012772:Shock, Septic / Q000503:physiopathology*; D013373:Substance P / Q000494:pharmacology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D008070:Lipopolysaccharides; D013373:Substance P; D005996:Nitroglycerin; D015740:Calcitonin Gene-Related Peptide