UNCOUPLING OF CORONARY MICROVASCULAR BETA-2-ADRENOCEPTORS BY ESCHERICHIA-COLI ENDOTOXEMIA

Background. Cardiovascular responses to the adrenergic stimulation are depressed in clinical and experimental endotoxemia. However, the effe ct of Escherichia coli endotoxemia on coronary microvascular beta-adre nergic function remains to be determined. The purpose of the present s tudy was to test the hypothesis that endotoxemia impairs the beta-adre noceptor- and adenosine 3'5'-cyclic monophosphate-mediated relaxation in the porcine coronary microcirculation. Methods. Coronary arterioles (80 to 170 mu m internal diameter) were isolated from pigs 3 hours af ter intravenous administration of E. coli endotoxin (150 mu g/kg, over 1 hour, n = 8) or Ringer's 8). Arterioles were studied in vitro in a pressurized, partialiy contracted, no-flow state by videomicroscopy. R esults. Precontracted (30% to 50% of baseline diameter with acetylchol ine) control coronary arterioles dilated in response to either the non selective beta-adrenoceptor agonist, isoproterenol, the G(s)-protein a ctivator, sodium flouride, or the adenylate cyclase activator, forskol in. After 3 hours of endotoxemia, the relaxation responses to isoprote renol and sodium flouride were significantly reduced, but the relaxati on response to forskolin was preserved. The beta(2)-adrenoceptor block er, ICI-118, 551, markedly reduced the relaxation of control microvess els induced by isoproterenol, whereas the beta(1)-adrenoceptor blocker , atenolol, caused only a slight reduction in isoproterenol-induced re laxation. Conclusions. beta(2)-Adrenoceptors appear to predominate ove r beta(1)-adrenoceptors in the coronary microcirculation. E. coli endo toxemia impairs beta(2)-adrenoceptor-mediated relaxation in the porcin e coronary microcirculation, apparently because of changes proximal to adenylate cyclase in the signal transduction pathway.