Nitric oxide: a mediator in anaphylactic shock in guinea-pigs.
In this study we show that the pathophysiology of anaphylaxis includes generation of nitric oxide (NO), a very powerful, short-acting vasodilator. Guinea-pigs sensitized to ovalbumin were treated with 200 microgram/kg diphenylene iodonium (DPI), and NO synthase inhibitor, prior to antigen challenge. Mortality following the challenge fell from 71 to 39% (p < 0.001, n = 59). In the Langendorff preparation perfused isolated hearts from sensitized guinea-pigs were challenged to initiate cardiac anaphylaxis. The coronary flow rate (CFR), a direct reflection of coronary arterial resistance, was reduced by antigen challenge to 56 +/- 4% (n = 16) of the basal rate. DPI (2 micrograms/ml) intensified the antigen-induced fall in CFR to 13 +/- 3% of control (p < 0.005, n = 5), and the false substrate for NO, L-N-methylarginine, to 37 +/- 3% (p < 0.05, n = 4). Sodium nitroprusside (SNP), a NO generator, raised the basal CFR by 46% (from 11.2 +/- 1.7 ml/min to 16.3 +/- 1.9 ml/min) and blunted the antigen-induced fall in CFR. Paradoxically, DPI, which can inhibit flavoprotein enzymes other than NO synthase, potentiated the vasodilator effect of SNP, raising the basal CFR by 116%. Together these results strongly indicate that the vasodilator NO is generated in anaphylaxis. However, whereas in the heart it may function as a counterweight to the vasospasm of the coronary arteries, in the intact animal it appears to be a major contributor to the potentially lethal hypotension of anaphylactic shock.
Abend
Y
Y
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
Ashkenazy
Y
Y
Witzling
V
V
Feigl
D
D
Geltner
D
D
Moshonov
S
S
Zor
U
U
D000707:Anaphylaxis / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D006168:Guinea Pigs; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009861:Onium Compounds / Q000494:pharmacology; D010047:Ovalbumin / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D009861:Onium Compounds; D015842:Serine Proteinase Inhibitors; D013439:Sulfhydryl Reagents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C007517:diphenyleneiodonium; D010047:Ovalbumin; D019001:Nitric Oxide Synthase