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.
Park
K W
KW
Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. kpark@bidmc.harvard.edu
Dai
H B
HB
Lowenstein
E
E
Sellke
F W
FW
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