Flow-induced dilation of rat coronary microvessels is attenuated by isoflurane but enhanced by halothane.
BACKGROUND
Volatile anesthetics attenuate agonist-induced endothelium-dependent vasodilation of coronary arteries. This study considered the hypothesis that the anesthetics may also attenuate flow-induced endothelium-dependent vasodilation.


METHODS
Rat subepicardial arteries of approximately 100 microm were monitored for diameter changes in vitro by a video detection system, with the midpoint luminal pressure held constant at 40 mmHg but the pressure gradient (and therefore flow) across each vessel increased from 0 to 80 mmHg, in the presence or absence of 1 or 2 minimum alveolar concentration (MAC) isoflurane or 1 or 2 MAC halothane, with or without 10 microM of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) or 10 microM of the cyclooxygenase inhibitor indomethacin.


RESULTS
Flow-induced dilation was attenuated by L-NNA or indomethacin (p < 0.001 each). It was attenuated by isoflurane in a concentration-dependent manner (P < 0.001). Attenuation by 2 MAC isoflurane persisted even in the presence of L-NNA (P < 0.01) or indomethacin (P < 0.05). On the other hand, flow-induced dilation was enhanced by 2 MAC halothane (P < 0.05). Halothane at 1 MAC had no significant effect. Enhancement by 2 MAC halothane was evident in the presence of indomethacin (P < 0.05) but not L-NNA (P = 0.40).


CONCLUSIONS
In rat subepicardial arteries, flow-induced dilation is endothelium-dependent and mediated by both NO and a prostanoid. Isoflurane attenuates flow-induced dilation, possibly by decreasing synthesis, the action of NO and a prostanoid, or both, whereas halothane enhances it, possibly by increasing synthesis, the action of NO, or both.
Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. kpark@bidmc.harvard.edu
K W
KW
Park
H B
HB
Dai
E
E
Lowenstein
F W
FW
Sellke
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D007530:Isoflurane; D006221:Halothane