Alterations of ex vivo vascular reactivity in intraperitoneal sepsis.
We examined vascular reactivity to vasoconstrictors [phenylephrine (PE), serotonin (5-HT), and high K+] and vasodilators [acetylcholine (ACh), A23187, L-arginine, and nitroglycerin (NTG)] in isolated mesenteric arterial rings from control and septic rats. Sepsis was induced by cecal ligation and puncture (CLP). A possible mechanism underlying CLP-induced alteration in vascular reactivity was also investigated with N omega-nitro-L-arginine (L-NNA 50 microM), methylene blue (MB 10 microM), and indomethacin (5 microM). In vivo, septic rats manifested two distinct hemodynamic phases, a hyperdynamic state during early (9 h after CLP) phase, followed by a hypodynamic state during late (18 h after CLP) phase. Therefore, we examined ex vivo vascular reactivity in these two phases. Results demonstrated that CLP operation caused hyporesponsiveness to contractile agents and hyperresponsiveness to vasodilator agents. After endothelium removal, most of the contractile responses were enhanced in both CLP-operated (9 and 18 h after operation) and sham-operated rats, whereas enhancement of high-K(+)-induced contraction was observed only in denuded rings from CLP 18-h rats. In addition, augmentation of relaxation induced by ACh at 9 or 18 h after CLP was abolished by N omega-nitro-L-arginine or MB but not by indomethacin. A possible mechanism responsible for alterations of vascular reactivity may be overproduction of nitric oxide (NO) which is blocked by L-NNA or MB.
Chen
S J
SJ
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Wu
C C
CC
Yen
M H
MH
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D002432:Cecum / Q000601:surgery; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001786:Blood Glucose; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D008751:Methylene Blue; D007213:Indomethacin