Contributions of nitric oxide, EDHF, and EETs to endothelium-dependent relaxation in renal afferent arterioles
✍ Scribed by Wang, Dan; Borrego-Conde, Lillian J.; Falck, John R.; Sharma, Kamalesh K.; Wilcox, Christopher S.; Umans, Jason G.
- Publisher
- Nature Publishing Group
- Year
- 2003
- Tongue
- English
- Weight
- 139 KB
- Volume
- 63
- Category
- Article
- ISSN
- 0085-2538
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✦ Synopsis
Background:
Acetylcholine-induced endothelium-dependent relaxation in the renal afferent arteriole has been ascribed to nitric oxide, but the role of endothelium-derived hyperpolarizing factors (edhfs) and 14,15-epoxyeicosatrienoic acid (14,15-eet) are unclear.
Methods:
Single afferent arterioles were dissected from kidney of normal rabbits and microperfused in vitro at 60 mm hg. vessels were preconstricted submaximally with norepinephrine (10(-8) mol/l). relaxation was assessed following cumulative addition of ach (10(-9) to 10(-4) mol/l) alone, or in the presence of indomethacin (to inhibit cyclooxygenase), nw-nitro-l-arginine (l-nna) (to inhibit nitric oxide synthase), methylene blue (to inhibit soluble guanylate cyclase), or a combination of l-nna + methylene blue. to assess contributions by edhf, studies were repeated with either apamin + charybdotoxin [to block ca2+-activated k+ channels (kca)] or with 40 mmol/l kcl. to asses the role of 14,15-eet, relaxations were evaluated in the presence of its competitive inhibitor 14,15-epoxyeicosa-5(z)-enoic acid (14,15-eeze).
Results:
Relaxation by acetylcholine was abolished following endothelial denudation. it was unaffected by indomethacin but was inhibited 54%+/- 5% (p < 0.001) by l-nna, 57%+/- 5% by methylene blue, and 60%+/- 4% by the combination of l-nna plus methylene blue. relaxation was inhibited further by kcl (80%+/- 6%) or by apamin + charybdotoxin (96%+/- 2%). 14,15-eeze, alone, inhibited acetylcholine-induced relaxation by 29%+/- 3%, and by 80%+/- 5% in the presence of l-nna.
Conclusion:
Acetylcholine-induced afferent arteriolar relaxation depends strongly on both nitric oxide, acting via soluble guanylate cyclase, and on an edhf, likely 14,15-eet, acting via kca.