Influence of aminoguanidine and the endothelin antagonist, SB 209670, on the regional haemodynamic effects of endotoxaemia in conscious rats.

摘要: 1. We compared the regional haemodynamic responses to lipopolysaccharide (LPS; 150 micrograms kg-1 h-1, i.v.) in presence of saline, aminoguanidine (AG; 45 mg bolus, h-1 infusion), or AG and non-selective endothelin receptor antagonist, SB 209670 (600 h-1), conscious, chronically instrumented, Long Evans rats (350-450 g; n = 8 all groups). used because there is evidence that it a selective inhibitor inducible nitric oxide synthase (iNOS), although recently has been claimed also inhibits constitutive NOS. 2. Infusion LPS saline caused an early, transient hypotension (1-2 h) renal vasodilatation, with secondary, delayed fall mean arterial blood pressure (MAP), progressive tachycardia, hindquarters vasodilatation. 3. alone rapid (within 30 s) rise MAP (delta 27 +/- 3 mmHg), accompanied by tachycardia vasoconstrictions, but no reduction flows, indicating pressor effect was, probably, largely due increase cardiac output. These effects are not consistent inhibiting In AG, still thereafter was significant (17 mmHg, h after onset infusion) bradycardia marked mesenteric vasoconstrictions. However, 23 co-infusion variables were different from baseline, except heart rate vascular conductance, which increased. 4. 209670, increases renal, conductances. Hence, prevented vasoconstrictions seen LPS, involvement these events. 5. infusion, AT 1-receptor losartan (10 kg-1), V d(CH2)5-0-Me-Tyr-AVP kg-1, 10 h-1) additional incremental falls Under circumstances, lower conductances higher than other experiments following administration d(CH2)5-0-Me-Tyr-AVP. Thus, findings iNOS, thereby revealing vasoconstrictor actions released clear activates very powerful hypotensive/vasodilator mechanism(s) resistant whose full influence only unmasked when endothelin, angiotensin II vasopressin inhibited.