Abstract | OBJECTIVE: Excessive opening of the adenosine triphosphate-sensitive potassium channel in vascular smooth muscle is implicated in the vasodilation and vascular hyporeactivity underlying septic shock. Therapeutic channel inhibition using sulfonylurea agents has proved disappointing, although agents acting on its pore appear more promising. We thus investigated the hemodynamic effects of adenosine triphosphate-sensitive potassium channel pore inhibition in awake, fluid-resuscitated septic rats, and the extent to which these responses are modulated by the high sympathetic tone present in sepsis. Temporal changes in ex-vivo channel activity and subunit gene expression were also investigated. DESIGN: In vivo and ex vivo animal study. SETTING: University research laboratory. SUBJECTS: Male adult Wistar rats. INTERVENTIONS AND MEASUREMENTS: MAIN RESULTS: A total of 120 rats (50 sham-operated controls, 70 septic) were included. Septic rats became hypotensive after 12 hrs, with a 24-hr mortality of 51.7% (0% in controls). At 6 hrs, there was an attenuated pressor response to norepinephrine (p < .01) despite blood pressure being elevated (p < .01). PNU-37883A had no pressor effect, except in the presence of pentolinium (p < .01). Kir6.1 subunit mRNA increased significantly in the mesenteric artery while rubidium efflux was increased in both the aorta and mesenteric artery at 24 hrs. CONCLUSIONS:
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Authors | Yi-Ling Chan, Nelson N Orie, Alex Dyson, Valerie Taylor, Raymond P Stidwill, Lucie H Clapp, Mervyn Singer |
Journal | Critical care medicine
(Crit Care Med)
Vol. 40
Issue 4
Pg. 1261-8
(Apr 2012)
ISSN: 1530-0293 [Electronic] United States |
PMID | 22425821
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ganglionic Blockers
- Morpholines
- U 37883A
- Pentolinium Tartrate
- Sodium-Potassium-Exchanging ATPase
- Adamantane
- Norepinephrine
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Topics |
- Adamantane
(analogs & derivatives, pharmacology)
- Animals
- Aorta
(drug effects, physiopathology)
- Blood Vessels
(drug effects, metabolism, physiopathology)
- Ganglionic Blockers
(pharmacology)
- Gene Expression
(drug effects, physiology)
- Male
- Mesenteric Arteries
(drug effects, physiopathology)
- Morpholines
(pharmacology)
- Norepinephrine
(pharmacology)
- Pentolinium Tartrate
(pharmacology)
- Rats
- Rats, Wistar
- Sepsis
(metabolism, physiopathology)
- Sodium-Potassium-Exchanging ATPase
(antagonists & inhibitors, metabolism, physiology)
- Vasodilation
(drug effects, physiology)
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