EFFECTS OF DEXAMETHASONE AND SB-209670 ON THE REGIONAL HEMODYNAMIC-RESPONSES TO LIPOPOLYSACCHARIDE IN CONSCIOUS RATS

1 Male (350-450 g) Long Evans rats were chronically instrumented to pe rmit regional haemodynamics to be monitored in the conscious state. In the first experiment, either saline (0.4 ml h(-1)) or dexamethasone ( 3 mg kg(-1), 125 mu g kg(-1) h(-1)) was infused continuously for 24 h, before co-infusion of lipopolysaccharide of (LPS, 150 mu g kg(-1) h(- 1)) for 24 h. Dexamethasone prevented the delayed (5-24 h) fall in mea n arterial blood pressure (MAP) and the renal and hindquarters vasodil atation seen with LPS infusion alone, but not the initial (about 2 h) fall in MAP or renal vasodilatation. However, at this dose, dexamethas one itself caused a significant rise in MAP and regional vasoconstrict ions. 2 In the second experiment, dexamethasone at a lower dose (12.5 mu g kg(-1) h(-1)) had only slight presser and vasoconstrictor effects . However, in its presence, infusion of LPS caused a substantial and p rogressive rise in MAP (maximum at 8 h, +32+/-3 mmHg) together with pe rsistent mesenteric and hindquarters vasoconstriction and a transient renal vasodilatation. 3 In the third experiment, the non-selective end othelin antagonist, SE 209670 (600 mu g kg(-1) h(-1)), blocked the sli ght presser and regional vasoconstrictor effects of the lower dose of dexamethasone. Furthermore, in the presence of dexamethasone and SE 20 9670, infusion of LPS caused marked, but transient hypotension (nadir at 5 h, -24+/-2 mmHg) and renal and mesenteric vasodilatation.4 At the end of all experimental protocols, sequential administration of the A T(1)-receptor antagonist, losartan, followed by the V-1-receptor antag onist, (+)-(CH2)(5)-O-Me-Tyr, vasopressin, caused effects indicating a variable involvement of angiotensin and vasopressin in the maintenanc e of cardiovascular status. 5 Collectively, the results indicate that, in the conscious rat, dexamethasone interacts with vasoconstrictor an d vasodilator mechanisms, and hence its influence on the haemodynamic responses to LPS cannot be attributed, simply, to inhibition of the ac tivity of inducible nitric oxide synthase and/or cyclo-oxygenase-2.