Regional haemodynamic responses to acetylcholine, methoxamine, salbutamol and bradykinin during lipopolysaccharide infusion in conscious rats.
1. The aim of the study was to assess the regional haemodynamic responsiveness to vasoconstrictor and vasodilator challenges during continuous 24 h infusion of lipopolysaccharide (LPS) in conscious Long Evans rats. 2. Rats were chronically instrumented for the measurement of regional haemodynamics (either internal and common carotid or renal, superior mesenteric and hindquarters) and received 3 min of infusions of acetylcholine (22 nmol min-1), methoxamine (120 nmol min-1), salbutamol (0.83 nmol min-1) and bradykinin (14.4 nmol min-1) at 2, 6 and 24 h after the start of saline or LPS (150 micrograms kg-1 h-1) infusion (rats with carotid probes received only acetylcholine and methoxamine). 3. During infusion of LPS there was a changing haemodynamic profile. After 2 h, there was a modest hypotension and vasodilatation in the internal carotid, renal and hindquarters vascular beds. After 6 h, arterial blood pressure had returned to baseline, there was still vasodilatation in the renal vascular bed but vasoconstriction in the internal and common carotids and the hindquarters. After 24 h, there was hypotension, tachycardia and generalized vasodilatation. 4. Acetylcholine caused a fall in blood pressure, tachycardia and hyperaemic vasodilatation in the carotid and renal vascular beds. Throughout the infusion of LPS, the carotid vasodilator response was enhanced after 2 h, reduced after 6 h and enhanced again after 24 h, whereas the renal vasodilator response to acetylcholine was either reduced (6 h) or absent (2 and 24 h); at this juncture the hypotensive response to acetylcholine was also enhanced and the tachycardia was reduced. 5. Methoxamine caused a rise in blood pressure, a fall in heart rate, and vasoconstriction in all the vascular beds monitored. During infusion of LPS, the pressor response to methoxamine was consistently reduced as were the vasoconstrictor responses in the carotid and mesenteric vascular beds, whereas the renal and hindquarters vasoconstrictor responses to methoxamine were only significantly reduced at some time points (renal 6 h, hindquarters 2 and 6 h).6. Salbutamol caused hypotension, tachycardia and hyperaemic vasodilatation, particularly in the hindquarters vascular bed. Throughout the infusion of LPS, the cardiovascular responses to salbutamol were substantially attenuated.7. Bradykinin caused hypotension, tachycardia and hyperaemic vasodilatation in the renal, mesenteric and hindquarters vascular beds. During the infusion of LPS, the hypotensive response to bradykinin was consistently augmented, and the tachycardia was consistently reduced, but the regional haemodynamic profile changed with time. Thus, after 2 h, the mesenteric vasodilator response was augmented and the hindquarters vasodilator response was reduced; after 6 h, the mesenteric vasodilator response appeared normal, but the renal and hindquarters vasodilator responses were reduced; after 24 h, the hindquarters vasodilator response was markedly augmented and the renal response had changed to a vasoconstriction.8. The present findings indicate marked regional variations in response to acetylcholine, methoxamine,salbutamol and bradykinin with time during LPS infusion. The changes observed are likely to reflect the interplay of a number of endogenous vasodilator and vasoconstrictor systems; further investigations will be required to clarify the mechanisms involved.
Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre.
J
J
Waller
S M
SM
Gardiner
T
T
Bennett
D000109:Acetylcholine / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D017536:Carotid Artery, Common / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D051381:Rats
D008070:Lipopolysaccharides; D008729:Methoxamine; D000109:Acetylcholine; D000420:Albuterol; D001920:Bradykinin