Abstract
In coronary resistance vessels, endothelium-derived hyperpolarizing factor (EDHF) plays an important role in endothelium-dependent vasodilation. EDHF has been proposed to be formed through cytochrome P-450 monooxygenase metabolism of arachidonic acid (AA). Our hypothesis was that AA-induced coronary microvascular dilation is mediated in part through a cytochrome P-450 pathway. The canine coronary microcirculation was studied in vivo (beating heart preparation) and in vitro (isolated microvessels). Nitric oxide synthase (NOS) (Nω-nitro-L-arginine, 100 μM) and cyclooxygenase (indomethacin, 10 μM) or cytochrome P-450 (clotrimazole, 2 μM) inhibition did not alter AA-induced dilation. However, when a Ca2+-activated K+ channel channel or cytochrome P-450 antagonist was used in combination with NOS and cyclooxygenase inhibitors, AA-induced dilation was attenuated. We also show a negative feedback by NO on NOS-cyclooxygenase-resistant AA-induced dilation. We conclude that AA-induced dilation is attenuated by cytochrome P-450 inhibitors, but only when combined with inhibitors of cyclooxygenase and NOS. Therefore, redundant pathways appear to mediate the AA response in the canine coronary microcirculation.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 281 |
| Issue number | 4 50-4 |
| State | Published - Oct 20 2001 |
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Keywords
- Coronary circulation
- Coronary microcirculation
- Intravital microscopy
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
Cite this
Endothelium-derived hyperpolarizing factor in coronary microcirculation : Responses to arachidonic acid. / Oltman, C. L.; Kane, N. L.; Fudge, J. L.; Weintraub, Neal Lee; Dellsperger, Kevin C.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 281, No. 4 50-4, 20.10.2001.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endothelium-derived hyperpolarizing factor in coronary microcirculation
T2 - Responses to arachidonic acid
AU - Oltman, C. L.
AU - Kane, N. L.
AU - Fudge, J. L.
AU - Weintraub, Neal Lee
AU - Dellsperger, Kevin C
PY - 2001/10/20
Y1 - 2001/10/20
N2 - In coronary resistance vessels, endothelium-derived hyperpolarizing factor (EDHF) plays an important role in endothelium-dependent vasodilation. EDHF has been proposed to be formed through cytochrome P-450 monooxygenase metabolism of arachidonic acid (AA). Our hypothesis was that AA-induced coronary microvascular dilation is mediated in part through a cytochrome P-450 pathway. The canine coronary microcirculation was studied in vivo (beating heart preparation) and in vitro (isolated microvessels). Nitric oxide synthase (NOS) (Nω-nitro-L-arginine, 100 μM) and cyclooxygenase (indomethacin, 10 μM) or cytochrome P-450 (clotrimazole, 2 μM) inhibition did not alter AA-induced dilation. However, when a Ca2+-activated K+ channel channel or cytochrome P-450 antagonist was used in combination with NOS and cyclooxygenase inhibitors, AA-induced dilation was attenuated. We also show a negative feedback by NO on NOS-cyclooxygenase-resistant AA-induced dilation. We conclude that AA-induced dilation is attenuated by cytochrome P-450 inhibitors, but only when combined with inhibitors of cyclooxygenase and NOS. Therefore, redundant pathways appear to mediate the AA response in the canine coronary microcirculation.
AB - In coronary resistance vessels, endothelium-derived hyperpolarizing factor (EDHF) plays an important role in endothelium-dependent vasodilation. EDHF has been proposed to be formed through cytochrome P-450 monooxygenase metabolism of arachidonic acid (AA). Our hypothesis was that AA-induced coronary microvascular dilation is mediated in part through a cytochrome P-450 pathway. The canine coronary microcirculation was studied in vivo (beating heart preparation) and in vitro (isolated microvessels). Nitric oxide synthase (NOS) (Nω-nitro-L-arginine, 100 μM) and cyclooxygenase (indomethacin, 10 μM) or cytochrome P-450 (clotrimazole, 2 μM) inhibition did not alter AA-induced dilation. However, when a Ca2+-activated K+ channel channel or cytochrome P-450 antagonist was used in combination with NOS and cyclooxygenase inhibitors, AA-induced dilation was attenuated. We also show a negative feedback by NO on NOS-cyclooxygenase-resistant AA-induced dilation. We conclude that AA-induced dilation is attenuated by cytochrome P-450 inhibitors, but only when combined with inhibitors of cyclooxygenase and NOS. Therefore, redundant pathways appear to mediate the AA response in the canine coronary microcirculation.
KW - Coronary circulation
KW - Coronary microcirculation
KW - Intravital microscopy
UR - http://www.scopus.com/inward/record.url?scp=0034786031&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034786031&partnerID=8YFLogxK
M3 - Article
C2 - 11557543
AN - SCOPUS:0034786031
VL - 281
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 4 50-4
ER -