Pages H1941–H1948: Randy S. Sprague, Alan H. Stephenson, Reed A. Dimmit, Neal A. Weintraub, Carrie A. Branch, Lorraine McMurdo, and Andrew J. Lonigro. “Effect of l-NAME on pressure-flow relationships in isolated rabbit lungs: role of red blood cells.” Page H1941: the author name of Neal A. Weintraub should read as Neal L. Weintraub.

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Bradykinin-induced relaxation of precontracted, porcine coronary artery (PCA) rings is mediated by distinctly different endothelium-derived relaxing factors depending on the contractile agent used. Thus when contracted with KC1, bradykinin-induced relaxation of PCA rings is mediated solely by nitric oxide (NO), whereas when contracted with the thromboxane mimetic U46619, a small component of the relaxation is attributable to NO and a large component is attributable to a non-NO mechanism that is independent of cyclooxygenase activity. We hypothesized that the non-NO component was mediated by arachidonic acid (AA) or by a non-cyclooxygenase product of AA metabolism. Bradykinininduced relaxations of PCA rings precontracted with U46619 in the presence of indomethacin (10 /imol/L) were moderately attenuated by the NO synthase inhibitor W-nitro-L-arginine methyl ester (L-NAME, 100 fxmolfL), whereas when precontracted with KC1, L-NAME abolished the relaxations. AA produced endothelium-dependent relaxations of rings precon-T he concept of the vascular endothelium as a fundamental participant in circulatory control is rapidly evolving.1 -2 In addition to several vasoconstricting agents, 3 -5 at least two vasorelaxing substances of vascular endothelial origin have been identified: prostaglandin I 2 (PGI 2 ), 6 a product of cyclooxygenase-mediated arachidonic acid metabolism, and nitric oxide (NO), 78 or a closely related compound, 9 which is produced by the action of NO synthase on L-arginine. More recently, endothelium-dependent relaxations of several vascular tissues have been reported to occur through a mechanism(s) distinct from one involving either cyclooxygenase or NO synthase.1013 Thus relaxation of isolated porcine coronary arterial (PCA) rings to bradykinin, for example, persisted despite inhibition of both cyclooxygenase and NO synthase. 1315 It was proposed that this relaxation was mediated by an endothelium-derived hyperpolarizing factor. 16Bradykinin activates phospholipase A 2 , 1718 purportedly through receptor-mediated increases in intracellular calcium. 19 The activation of phospholipase A 2 results in hydrolysis of tissue phospholipids, in turn releasing fatty acids, including arachidonic acid. traded with U46619 that were unaffected by L-NAME, whereas AA did not relax rings precontracted with KC1. In rings precontracted with U46619, in the presence of L-NAME and indomethacin the phospholipase inhibitors quinacrine (50 fimolfL) and 4-bromophenacyl bromide (10 jtmol/L) attenuated bradykinin-but not AA-induced relaxations. Key Words • endothelium-derived relaxing factor • coronary artery • arachidonic acid • bradykinin acid may in turn be reacylated 21 or metabolized further through three known pathways, ie, the cyclooxygenase pathway* to prostaglandins and thromboxanes, the lipoxygenase pathway 22 to leukotrienes and oxygenated fatty acids, and the cytochrome P-450 monooxygenase pathway 23 to epoxides and oxygenated fatty acids. Several of the non-cyclooxygenase-mediated products of arachidonic...

Cocaine use and behavioral stress elicit variable cardiovascular responses in individuals. In the present study, we examined the effects of cocaine or stress on arterial pressure, heart rate, and cardiac output in conscious rats. Rats were instrumented for determination of ascending aortic blood flow as an index of cardiac output using pulsed Doppler flow-metry. Cocaine administration elicited consistent decreases in cardiac output in some rats, whereas others had increases. In contrast, the pressor and heart rate responses were similar in these two groups of animals. Air jet stress also elicited a decrease in cardiac output only in a subset of conscious rats, yet produced equivalent pressor responses in all rats. Cardiac output responses to cocaine and air jet stress were closely correlated in individual rats, indicating that these stimuli evoke similar hemodynamic responses in individual rats. These observations suggest that the rat may provide a model for understanding differential cardiovascular sensitivity to cocaine and/or stress in humans.