The effects of isoflurane on airway smooth muscle crossbridge kinetics in Fisher and Lewis rats.
Our aim was to determine how isoflurane modified crossbridge (CB) number and kinetics in airway smooth muscle (ASM) and to compare its effects in Fisher and Lewis rats, two strains with differences in airway responsiveness. The effects of isoflurane (2 MAC) on isotonic and isometric contractility in tracheal ASM strips were investigated after methacholine (10(-6) M)-induced contraction. CB mechanics and kinetics were analyzed using the formalism of Huxley's equations adapted to ASM. After isoflurane, maximum velocity did not differ from baseline in Lewis rats, whereas it was significantly less than baseline in Fisher rats ( approximately 25%), the most reactive strain. Isoflurane totally reversed methacholine-induced increase in active CB number in Lewis rats (2.4 +/- 0.5 versus 1.8 +/- 0.4 10(9)/mm(2) after methacholine and isoflurane, respectively) whereas reversal was only partial in Fisher rats (2.7 +/- 0.4 versus 2.1 +/- 0.3 10(9)/mm(2) after methacholine and isoflurane, respectively). Isoflurane induced a 40% increase in attachment step duration in both strains and an almost twofold increase in the CB cycle duration compared with baseline in Lewis rats. The isoflurane-induced increase in detachment step duration was less in Lewis than in Fisher rats (P < 0.05). We concluded that isoflurane modulated CB number and CB cycling rates of isolated rat ASM differently depending on the level of airway responsiveness.
Laboratory of Pathophysiologie cellulaire et moléculaire de l'insuffisance cardiaque, Institut National de la Santé et de la Recherche Médicale INSERM U572 Centre Hospitalo-Universitaire Lariboisière, Assistance Publique-Hôpitaux de Paris, France.
Caroline
C
Duracher
François-Xavier
FX
Blanc
Pierre-Yves
PY
Gueugniaud
Jean Stéphane
JS
David
Bruno
B
Riou
Yves
Y
Lecarpentier
Catherine
C
Coirault
D000465:Algorithms; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012137:Respiratory System / Q000187:drug effects*; D013045:Species Specificity; D014132:Trachea / Q000187:drug effects
D018685:Anesthetics, Inhalation; D007530:Isoflurane