Regional haemodynamic responses to acetylcholine, methoxamine, salbutamol and bradykinin during lipopolysaccharide infusion in conscious rats

Abstract

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-'), methoxamine (120 nmol min-'), salbutamol (0.83 nmol min-') and bradykinin (14.4 nmol min-') at 2, 6 and 24 h after the start of saline or LPS (150 ;g kg-' h-') 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 indica...

Maintenance of Renal Vascular Reactivity Contributes to Acute Renal Failure during Endotoxemic Shock

“…To our knowledge, only one study has assessed the effect of vasoconstrictor agents on renal resistance arterioles from septic animals. A 24-h infusion of LPS leads to markedly reduced responsiveness to ␣-adrenoceptor stimulation (for 3 min) in carotid and mesenteric vascular beds in conscious rats, whereas renal vascular reactivity approximated normal (33). Thus, there is a clear pattern of heterogeneity, with vascular reactivity differing among organs and different constrictor substances.…”

Enhancement of the haemodynamic effects of NG‐monomethyl‐l‐arginine by transforming growth factor‐β1 in conscious, normal, but not endotoxaemic, rats

“…To achieve our objectives, we investigated the regional haemodynamic effects of TGF-f, in conscious control rats, and in rats receiving a constant infusion of LPS (Waller et al, 1994). In the same animals we then determined if fluenced responses to L-NMMA.…”

Effects of in Vivo Lipopolysaccharide Infusion on Vasoconstrictor Function of Rat Isolated Mesentery, Kidney, and Aorta

“…In that model, we have shown regionally selective changes in cardiovascular status (Waller et al, 1994;Gardiner et al, 1993Gardiner et al, , 1994Gardiner et al, , 1995Gardiner et al, , 1996a associated with reduced mesenteric vasoconstrictor responses to methoxamine (an ␣ 1 -adrenoceptor agonist) in vivo at 2 and 24 h after the start of LPS infusion (Waller et al, 1994;Tarpey et al, 1998a). In contrast, the renal vasoconstrictor response to methoxamine in vivo was not suppressed (Waller et al, 1994).…”

“…In that model, we have shown regionally selective changes in cardiovascular status (Waller et al, 1994;Gardiner et al, 1993Gardiner et al, , 1994Gardiner et al, , 1995Gardiner et al, , 1996a associated with reduced mesenteric vasoconstrictor responses to methoxamine (an ␣ 1 -adrenoceptor agonist) in vivo at 2 and 24 h after the start of LPS infusion (Waller et al, 1994;Tarpey et al, 1998a). In contrast, the renal vasoconstrictor response to methoxamine in vivo was not suppressed (Waller et al, 1994). Interestingly, mesenteric bed preparations taken from animals infused with LPS and investigated in vitro did not show reduced vasoconstrictor effects of methoxamine (Tarpey and Randall, 1998), but this may have been due to the mode of administration, since others who have investigated mesenteric arteries isolated from LPS-treated animals have noted an impairment in the sustained contractile response, even though the initial response to agonist exposure was normal (Martinez et al, 1996;Mitolo-Chieppa et al, 1996).…”

“…In cases of severe infection, this can result in septic shock, characterized by unrelenting hypotension, tachycardia, and increased cardiac output. These effects can be simulated by the administration of the bacterial toxin lipopolysaccharide (LPS) in both humans (Suffredini et al, 1989) and animals (Waller et al, 1994;Gardiner et al, 1995;Pastor, 1999;Zhou et al, 2001). The effect of endotoxemia on the vasculature has been studied by many different groups, in vitro, and also ex vivo, in preparations isolated from animals following the administration of LPS.…”