SHORT EXPOSURE TO ENDOTOXIN INCREASES THE CONSTRICTION INDUCED BY ANGIOTENSIN-II IN RAT AORTA

The contraction elicited by angiotensin II (ANG II) was studied by usi ng standard isometric tension techniques in aortic rings exposed for I h to 1 or 10 mu g/ml Escherichia coli lipopolysaccharide endotoxin (LP S). This contraction was 18 and 71% greater for the two doses of LPS, respectively, than in unexposed control rings. In endothelium-denuded rings, the LPS-induced increase in contraction in response to ANG II w as completely abolished. Because the contraction induced by ANG II is modulated by the simultaneous release of prostaglandins, we tested the hypothesis that LPS interferes with this modulation. We found that th e LPS-induced increase in contraction to ANG II was inhibited in the p resence of the cyclooxygenase inhibitor indomethacin (10(-5) M) or the prostaglandin H-2/thromboxane A(2)-receptor antagonist SQ-29548 (2 x 10(-7) M). Conversely, the LPS-induced increase in contraction in resp onse to ANG II was not inhibited by the presence of dexamethasone (10( -6) M), which inhibits new protein synthesis. In addition, there was n o loss of vasodilator response to the endothelium-dependent receptor a gonist acetylcholine (10(-8)-10(-4) M) or in the constrictor responses to norepinephrine (10(-9)-10(-5) M) and KCl (20-100 mM). We conclude that short exposure to LPS produces a specific increase in the constri ctor response to ANG II via mechanisms mediated by prostaglandin H-2/t hromboxane A(2). This effect could be a LPS-induced shift in favor of constrictor prostanoids in the balance of dilator/constrictor prostano ids, the release of which is associated with stimulation by ANG II.