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-r elated peptide, and substance P play in tissue-blood flow regulation d uring early septic shock, we examined the responsiveness of arteries r emoved from pigs 3 h after administration of Escherichia coli lipopoly saccharide or saline vehicle. The carotid, cranial mesenteric, and lef t anterior descending coronary arteries were excised, and rings were c ut from each vessel. Constrictor responses were obtained to cumulative doses of norepinephrine or potassium chloride. Rings were reconstrict ed and challenged with acetylcholine, substance P, calcitonin gene-rel ated peptide, and nitroglycerin. Lipopolysaccharide significantly incr eased the cranial mesenteric artery's response to high concentrations of norepinephrine and the response to nitroglycerin in all vessels. Th is enhancement of responses to nitroglycerin suggests augmented smooth -muscle responsiveness to an exogenous source of nitric oxide, possibl y associated with early depression of basal endothelial function. Depr ession of agonist-induced nitric oxide release may mask such enhanceme nt with endothelial-dependent dilators and may enhance the response to adrenergic constrictors in some vascular beds.