Endogenous nitric oxide reduces the efficacy of the endothelin system to maintain blood pressure during high epidural anaesthesia in conscious dogs

Abstract

The diminished increase in mean arterial pressure after injection of N-omega-nitro-arginine-methylester only during endothelin receptor blockade indicates that endogenous nitric oxide inhibits the action of endothelin during high epidural anaesthesia and might thus explain the reduced efficacy of endothelin in maintaining blood pressure during high epidural anaesthesia.

Acute nitric oxide synthase inhibition and endothelin-1-dependent arterial pressure elevation

“…ET A and ET A/B receptor antagonist also reduced NOS inhibitor-elevated pressure (Qiu et al, 1995; Richard et al, 1995; Thompson et al, 1995; Banting et al, 1996; Gardiner et al, 1996; Filep, 1997; Gellai et al, 1997; Gratton et al, 1997; Fink et al, 1998; Hashimoto et al, 1998; Ming et al, 1998; Thorin et al, 1999; Montanari et al, 2000; Kramp et al, 2001; Schmidt et al, 2001; Gomez-Alamillo et al, 2003; Hubloue et al, 2003; Merkus et al, 2006; Beck et al, 2007; Czóbel et al, 2009; de Beer et al, 2011; Bourque et al, 2012; Brochu et al, 2013; Figure 1 ). In a large majority of these studies the reduced NOS inhibitor-elevated pressure occurred in the absence of decreased basal pressure due to ET A /ET A/B receptor antagonist (Qiu et al, 1995; Richard et al, 1995; Thompson et al, 1995; Banting et al, 1996; Filep, 1997; Gellai et al, 1997; Gratton et al, 1997; Fink et al, 1998; Thorin et al, 1999; Montanari et al, 2000; Schmidt et al, 2001; Hubloue et al, 2003; Beck et al, 2007; Figure 1 ), while in several studies ET A /ET A/B receptor antagonist decreased basal pressure (Hashimoto et al, 1998; Kramp et al, 2001; Gomez-Alamillo et al, 2003; Merkus et al, 2006; de Beer et al, 2011; Figure 1 ).…”

“…Indeed, at successively greater NOS inhibitor doses, which induced greater magnitudes of pressure elevation, ET receptor antagonist caused increasingly larger percent inhibitions of NOS inhibitor-elevated pressure (Richard et al, 1995; Filep, 1997; Beck et al, 2007). That is, the relative ratio of the ET-1-dependent to -independent components of the NOS inhibitor-elevated pressure increased with NOS inhibitor dose and also, therefore, with greater amounts of NOS inhibitor-induced pressure elevation (Richard et al, 1995; Filep, 1997; Beck et al, 2007). The dose range of the NOS inhibitor, N ω -nitro- L -arginine methyl ester (L-NAME, intravenous bolus), in rat was 0.1–3 mg/kg (Richard et al, 1995) and 0.125–2 mg/kg (Filep, 1997), with maximal increased mean arterial pressure achieved at 1 mg/kg.…”

“…In a large majority of these studies the reduced NOS inhibitor-elevated pressure occurred in the absence of decreased basal pressure due to ET A /ET A/B receptor antagonist (Qiu et al, 1995; Richard et al, 1995; Thompson et al, 1995; Banting et al, 1996; Filep, 1997; Gellai et al, 1997; Gratton et al, 1997; Fink et al, 1998; Thorin et al, 1999; Montanari et al, 2000; Schmidt et al, 2001; Hubloue et al, 2003; Beck et al, 2007; Figure 1 ), while in several studies ET A /ET A/B receptor antagonist decreased basal pressure (Hashimoto et al, 1998; Kramp et al, 2001; Gomez-Alamillo et al, 2003; Merkus et al, 2006; de Beer et al, 2011; Figure 1 ). The relative magnitudes of the ET A /ET A/B receptor antagonist-sensitive component of the NOS inhibitor-elevated pressure also varied greatly, ranging from 0 to 100% (Qiu et al, 1995; Richard et al, 1995; Thompson et al, 1995; Banting et al, 1996; Filep, 1997; Gellai et al, 1997; Gratton et al, 1997; Fink et al, 1998; Thorin et al, 1999; Montanari et al, 2000; Schmidt et al, 2001; Gomez-Alamillo et al, 2003; Hubloue et al, 2003; Beck et al, 2007; Czóbel et al, 2009; Brochu et al, 2013; Figure 1 ). The variability was not due to the use of:…”

“…(b) Different species, since amongst dog and rat studies the reductions of the NOS inhibitor-elevated pressure by ET A/B receptor antagonists both ranged considerably, i.e., from 0 to 100% (Thorin et al, 1999; Gomez-Alamillo et al, 2003; Hubloue et al, 2003; Beck et al, 2007) and 23–67% (Qiu et al, 1995; Richard et al, 1995; Banting et al, 1996; Filep, 1997; Gellai et al, 1997; Fink et al, 1998), respectively ( Figure 1 ).…”

“…Specifically, in several studies in which the effects of ET receptor antagonist on both NOS inhibitor and exogenous ET-1- and big ET-1-elevated pressure were examined, the ET receptor antagonist greatly inhibited the elevated pressure due to ET-1/big ET-1 even though the ET-1/big ET-1 dose generally induced a greater increase in pressure than the NOS inhibitor (Thompson et al, 1995; Filep, 1997; Gratton et al, 1997; Fink et al, 1998; Hubloue et al, 2003; Beck et al, 2007). However, an untested (to our knowledge) assumption underlying this comparative analysis of the inhibitory efficacy of ET receptor antagonist toward the NOS inhibitor- and ET-1-/big ET-1-elevated pressure is whether ET receptor antagonist efficacy is reduced by cellular events associated with NOS inhibition.…”