Temporal differences between the involvement of angiotensin II and endothelin in the cardiovascular responses to endotoxaemia in conscious rats

• Published in: British journal of pharmacology 1996-12, Vol.119 (8), p.1619-1627
• Main Authors: Gardiner, S.M., Kemp, P.A., March, J.E., Bennett, T.
• Format: Article
• Language: English
• Subjects: angiotensin II; Angiotensin II - metabolism; Angiotensin II - physiology; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Arginine Vasopressin - analogs & derivatives; Arginine Vasopressin - pharmacology; Biological and medical sciences; Biphenyl Compounds - pharmacology; captopril; Captopril - pharmacology; d(CH2)5‐O‐Me‐Tyr‐AVP; endothelin; Endothelins - physiology; Endotoxemia - physiopathology; Fundamental and applied biological sciences. Psychology; Hemodynamics - physiology; Hemodynamics. Rheology; Imidazoles - pharmacology; Indans - pharmacology; Lipopolysaccharide; Lipopolysaccharides; Losartan; Male; Rats; Renal Circulation - drug effects; SB 209670; Tetrazoles - pharmacology; vasopressin; Vasopressins - physiology; Vertebrates: cardiovascular system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1996.tb16081.x

1 Male, Long Evans rats were instrumented chronically with pulsed Doppler probes and intravascular catheters to allow assessment of regional haemodynamic changes during i.v. infusion of lipopolysaccharide (LPS, 150 μg kg−1 h−1). 2 In the presence of the AT1‐receptor antagonist, losartan (10 mg kg−1 + 10 mg kg−1 h−1), the initial (1–2 h) hypotensive and renal, mesenteric and hindquarters vasodilator responses to LPS were enhanced significantly. Thereafter these effects waned, but between 8–23 h after the onset of LPS infusion, a further fall in mean arterial blood pressure (MAP) and increases in renal and hindquarters flows and conductances occurred. All these changes were significantly greater than seen with losartan or LPS alone, and exceeded the sum of their effects. 3 In the presence of captopril (2 mg kg−1 + 2 mg kg−1 h−1), the initial hypotensive and renal vasodilator responses to LPS were enhanced, but less so than in the presence of losartan. However, the effects of LPS in the presence of losartan and captopril together were not different from those in the presence of losartan alone. These observations indicate that the ability of captopril to inhibit the degradation of bradykinin had no additional influence, and the differences between the effect of captopril and losartan on the initial effects of LPS were probably due to more effective suppression of the action of angiotensin II by losartan. 4 In the absence of LPS, co‐infusion of losartan and the non‐selective endothelin antagonist, SB 209670 (600 μg kg−1 + 600 μg kg−1 h−1), caused a substantial, progressive hypotension (−25 ± 2 mmHg at 24 h) accompanied by increases in renal, mesenteric and hindquarters vascular conductances (31 ± 13, 44 ± 9 and 45 ± 12%, respectively), indicating an involvement of angiotensin II and endothelin in the maintenance of normal cardiovascular status in conscious, Long Evans rats. 5 In the presence of losartan and SB 209670, the initial, LPS‐induced fall in MAP (−42 ± 2 mmHg) was not different from that in the presence of losartan (−39 ± 4 mmHg), and the increases in renal, in mesenteric, and in hindquarters vascular conductances were similar in the two conditions. However, there was no recovery in MAP, and there were persistent renal, mesenteric and hindquarter vasodilatations. 6 In all experiments involving LPS, administration of the V1‐receptor antagonist, d(CH2)5‐O‐Me‐Tyr‐AVP (10 μg kg−1), 23 h after the start of LPS infusion caused additional hypotension and mese