Decreased aortic smooth muscle contraction in a rat model of multibacterial sepsis.
We investigated whether blockade of the smooth muscle cell (SMC) inducible nitric oxide synthase (iNOS)-soluble guanylyl cyclase (sGC) vasodilator pathway would restore the fall in vasoreactivity produced by sepsis following cecal ligation and perforation (CLP) in rats. Contraction of adjacent aortic rings paired for the presence or absence of endothelial cells (EC) was recorded following high [K(+)](e) (40 mm) or norepinephrine (NE, 10(-8) to 10(-5) m) in the presence of the nitric oxide synthase inhibitor (NOS), N(G)-nitro-l-arginine methyl ester (l-NAME, 0.3 mm) or the sGC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 5 mum). In EC-denuded rings, sepsis halved SMC contraction induced by high [K(+)](e) or NE; neither l-NAME nor ODQ produced an increase in NE E(max) or high [K(+)](e)-evoked contraction. In conclusion, SMC contractility is globally reduced in CLP; this reduction does not appear to be explained by induction of SMC NOS in this CLP model.
Wang
Changhua
C
Department of Physiology, School of Medicine, Wuhan University, 185 Donghu Road, 430071 Wuhan, China.
Mansard
Arnaud
A
Giummelly
Philippe
P
Atkinson
Jeffrey
J
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D018805:Sepsis / Q000382:microbiology* / Q000503:physiopathology*; D000071756:Soluble Guanylyl Cyclase
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; D018160:Receptors, Cytoplasmic and Nuclear; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D019331:NG-Nitroarginine Methyl Ester