Effects of NO/cGMP inhibitors in a rat model of anaphylactoid shock

Abstract

Anaphylactic shock can be defined as an acute syndrome, and it is the most severe clinical manifestation of allergic diseases. Anaphylactoid reactions are similar to anaphylactic events but differ in the pathophysiological mechanism. Nitric oxide (NO) inhibitors during anaphylaxis suggest that NO might decrease the signs and symptoms of anaphylaxis but exacerbate associated vasodilation. Therefore, blocking the effects of NO on vascular smooth muscle by inhibiting the guanylate cyclase (GC) would be a reasonable strategy. This study aimed to investigate the effects of NO/cGMP pathway inhibitors methylene blue (MB), N o-nitro-L-arginine methyl ester hydrochloride (L-NAME), and indigo carmine (IC) in shock induced by compound 48/80 (C48/80) in rats. The effect was assessed by invasive blood pressure measurement. Shock was initiated by C48/80 intravenous bolus injection 5 min before (prophylactic) or after (treatment) the administration of the inhibitors MB (3 mg/kg), L-NAME (1 mg/kg), and IC (3 mg/kg). Of the groups that received drugs as prophylaxis for shock, only the IC group did not present the final systolic blood pressure (SBP) better than the C48/80 group. Regarding shock treatment with the drugs tested, all groups had the final SBP similar to the C48/80group. Altogether, our results suggested that inhibition of GC and NO synthase in NO production pathway was not sufficient to revert hypotension or significantly improve survival.

Effect of Nitric Oxide Pathway Inhibition on the Evolution of Anaphylactic Shock in Animal Models: A Systematic Review

“…Nine hundred ninety unique studies were found in the literature search and screened for eligibility based on title/abstract screening against the pre-set inclusion and exclusion criteria. Of the 135 studies identified as eligible for full-text screening, 17 studies were finally selected for inclusion in the review [10,14,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. A detailed PRISMA flow diagram regarding the screening and selection process is available in Figure 3.…”

“…First, we grouped the studies based on their status as pre-treatment or post-treatment studies. Five studies had experimental models for both [25][26][27][28]35]. We next organized the studies according to animal species.…”

“…We next organized the studies according to animal species. Two studies used dogs [29,30], five used rats [14,25,[31][32][33], five used mice [10,23,24,34,37], three used pigs [26,28,35] and two studies used rabbits [27,36]. The characteristics are summarized in Tables 1 and 2.…”

“…Note that some studies had experimental groups for more than one medication. Twelve studies used NG-nitro-L-arginine methyl ester (L-NAME) [10,14,[23][24][25][29][30][31][32]34,36,37], seven studies used methylene blue (MB) [10,23,25,27,28,33,35], two studies used indigo carmine (IC) [25,26], one study used Aminoguanidine (AG) [32], one used 7-Nitroindazole (7-NI) [32] and two used 1H- [1,2,4] Oxadiazole [4,3-a] quinoxalin-1-one (ODQ) [10,23].…”

“…Indigo carmine (IC) inhibits endothelium-dependent vasodilation, affects peripheral alpha constrictors [25] and may inhibit sGC [41]. IC acts downstream of membrane receptors and involves cytosolic calcium [41].…”