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Mechanisms of nitric oxide-independent relaxations induced by carbachol and acetylcholine in rat isolated renal arteries.
Br J Pharmacol. 2000 Jul; 130(6):1191-200.BJ

Abstract

1. In rat isolated renal artery segments contracted with 0.1 microM phenylephrine and in the presence of the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME), carbachol and acetylcholine produced endothelium-dependent relaxations. The mechanisms underlying these relaxations were studied. 2. These relaxations were not affected by ODQ (1H-[1,2,4]oxadiazolo[4,3, -a]quinoxalin-1-one) or indomethacin. In arteries contracted with 20 - 30 mM K(+), L-NAME-resistant relaxations induced by carbachol and acetylcholine were virtually absent. 3. The Na(+)-K(+) ATPase inhibitor ouabain reduced these relaxations in a concentration-dependent manner. 4. In K(+)-free media, addition of K(+) (5 mM) produced 90. 5+/-3.9% (n=3) relaxation of phenylephrine-induced tone. This relaxation was endothelium-independent and ouabain-sensitive. 5. Tetraethylammonium (TEA), charybdotoxin (ChTX) and iberiotoxin (IbTX) reduced the sensitivity of carbachol-induced relaxations, but did not change the maximal response. These relaxations were not altered by 4-aminopyridine (4-AP), glibenclamide or apamin. Acetylcholine (1 microM)-induced relaxation was reduced by ChTX, but not by TEA or IbTX. 6. The cytochrome P450 inhibitor miconazole, but not 17-octadecynoic acid, reduced the sensitivity of carbachol-induced relaxations, without changing the maximal response. 7. In conclusion, in rat isolated renal arteries, acetylcholine and carbachol produced a non-NO/non-PGI(2) relaxation which is mediated by an endothelium-derived hyperpolarizing factor (EDHF). This factor does not appear to be a cytochrome P450 metabolite. The inhibition by ouabain of these relaxations suggests the possible involvement of Na(+)-K(+) ATPase activation in EDHF responses, although other mechanisms cannot be totally ruled out.

Authors+Show Affiliations

Pharmacology Research Group, Department of Medical Laboratory Science, RMIT University, Melbourne, Victoria, Australia.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10903955

Citation

Jiang, F, et al. "Mechanisms of Nitric Oxide-independent Relaxations Induced By Carbachol and Acetylcholine in Rat Isolated Renal Arteries." British Journal of Pharmacology, vol. 130, no. 6, 2000, pp. 1191-200.
Jiang F, Li CG, Rand MJ. Mechanisms of nitric oxide-independent relaxations induced by carbachol and acetylcholine in rat isolated renal arteries. Br J Pharmacol. 2000;130(6):1191-200.
Jiang, F., Li, C. G., & Rand, M. J. (2000). Mechanisms of nitric oxide-independent relaxations induced by carbachol and acetylcholine in rat isolated renal arteries. British Journal of Pharmacology, 130(6), 1191-200.
Jiang F, Li CG, Rand MJ. Mechanisms of Nitric Oxide-independent Relaxations Induced By Carbachol and Acetylcholine in Rat Isolated Renal Arteries. Br J Pharmacol. 2000;130(6):1191-200. PubMed PMID: 10903955.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of nitric oxide-independent relaxations induced by carbachol and acetylcholine in rat isolated renal arteries. AU - Jiang,F, AU - Li,C G, AU - Rand,M J, PY - 2000/7/25/pubmed PY - 2000/9/19/medline PY - 2000/7/25/entrez SP - 1191 EP - 200 JF - British journal of pharmacology JO - Br J Pharmacol VL - 130 IS - 6 N2 - 1. In rat isolated renal artery segments contracted with 0.1 microM phenylephrine and in the presence of the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME), carbachol and acetylcholine produced endothelium-dependent relaxations. The mechanisms underlying these relaxations were studied. 2. These relaxations were not affected by ODQ (1H-[1,2,4]oxadiazolo[4,3, -a]quinoxalin-1-one) or indomethacin. In arteries contracted with 20 - 30 mM K(+), L-NAME-resistant relaxations induced by carbachol and acetylcholine were virtually absent. 3. The Na(+)-K(+) ATPase inhibitor ouabain reduced these relaxations in a concentration-dependent manner. 4. In K(+)-free media, addition of K(+) (5 mM) produced 90. 5+/-3.9% (n=3) relaxation of phenylephrine-induced tone. This relaxation was endothelium-independent and ouabain-sensitive. 5. Tetraethylammonium (TEA), charybdotoxin (ChTX) and iberiotoxin (IbTX) reduced the sensitivity of carbachol-induced relaxations, but did not change the maximal response. These relaxations were not altered by 4-aminopyridine (4-AP), glibenclamide or apamin. Acetylcholine (1 microM)-induced relaxation was reduced by ChTX, but not by TEA or IbTX. 6. The cytochrome P450 inhibitor miconazole, but not 17-octadecynoic acid, reduced the sensitivity of carbachol-induced relaxations, without changing the maximal response. 7. In conclusion, in rat isolated renal arteries, acetylcholine and carbachol produced a non-NO/non-PGI(2) relaxation which is mediated by an endothelium-derived hyperpolarizing factor (EDHF). This factor does not appear to be a cytochrome P450 metabolite. The inhibition by ouabain of these relaxations suggests the possible involvement of Na(+)-K(+) ATPase activation in EDHF responses, although other mechanisms cannot be totally ruled out. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/10903955/Mechanisms_of_nitric_oxide_independent_relaxations_induced_by_carbachol_and_acetylcholine_in_rat_isolated_renal_arteries_ L2 - https://doi.org/10.1038/sj.bjp.0703408 DB - PRIME DP - Unbound Medicine ER -