In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 17 ( 2000-08-15), p. 9747-9752
Abstract:
In addition to nitric oxide (NO) and prostacyclin (PGI 2 ), the endothelium generates the endothelium-derived hyperpolarizing factor (EDHF). We set out to determine whether an EDHF-like response can be detected in wild-type (WT) and endothelial NO synthase knockout mice (eNOS −/−) mice. Vasodilator responses to endothelium-dependent agonists were determined in vivo and in vitro. In vivo , bradykinin induced a pronounced, dose-dependent decrease in mean arterial pressure (MAP) which did not differ between WT and eNOS −/− mice and was unaffected by treatment with N ω -nitro- l -arginine methyl ester and diclofenac. In the saline-perfused hindlimb of WT and eNOS −/− mice, marked N ω -nitro- l -arginine ( l -NA, 300 μmol/liter)- and diclofenac-insensitive vasodilations in response to both bradykinin and acetylcholine (ACh) were observed, which were more pronounced than the agonist-induced vasodilation in the hindlimb of WT in the absence of l -NA. This endothelium-dependent, NO/PGI 2 -independent vasodilatation was sensitive to KCl (40 mM) and to the combination of apamin and charybdotoxin. Gap junction inhibitors (18α-glycyrrhetinic acid, octanol, heptanol) and CB-1 cannabinoid-receptor agonists (Δ 9 -tetrahydrocannabinol, HU210) impaired EDHF-mediated vasodilation, whereas inhibition of cytochrome P450 enzymes, soluble guanylyl cyclase, or adenosine receptors had no effect on EDHF-mediated responses. These results demonstrate that in murine resistance vessels the predominant agonist-induced endothelium-dependent vasodilation in vivo and in vitro is not mediated by NO, PGI 2 , or a cytochrome P450 metabolite, but by an EDHF-like principle that requires functional gap junctions.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.97.17.9747
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2000
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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