Korean J Anesthesiol.  2005 Mar;48(3):293-302. 10.4097/kjae.2005.48.3.293.

Influence of Myoendothelial Gap Junction on the Regulation of Vasomotor Tone

• Huh J
• Ro YJ
• Min SW
• Kim CS
• Kang SS
• Jung IY
• Park WS
• Chung SH
• Bahk JH

• KMID: 2091978
• DOI: http://doi.org/10.4097/kjae.2005.48.3.293

Abstract

BACKGROUND: In addition to nitric oxide (NO) and prostacyclin (PGI2), there is another endothelium-derived mechanism of smooth muscle relaxation, which is associated with an endothelium-derived hyperpolarizing factor (EDHF). To assess the role of gap junctions in endothelium dependent hyperpolarization, we investigated the relationship between distribution of myoendothelial gap junction (MEGJ) and relative importance of the EDHF pathway in the regulation of vascular tone.
METHODS
Immunohistochemistry and confocal microscopic examination of the mesenteric arterial wall of male Sprague-Dawley rat following treatment with specific antibodies were performed to delineate the distribution of connexin 43, a gap junctional protein. The standard dose-response curve for acetylcholine (10-9-10-5 M) of the mesenteric artery was regarded as the release of EDHF in the presence of the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 10-4 M) and indomethacine (10-5 M). The effects of the gap junction inhibitors such as 18alpha-glycyrrhetinic acid (18alpha-GA; (2 x 10-4 M)) and carbenoxolone (3 x 10-4 M) was assessed regarding relaxtion to acetylcholine, contraction to phenylephrine (5 x 10-6 M) in the proximal and distal mesenteric arteries.
RESULTS
In the distal artery, gap junctional plaques were more prevalent, and the relaxation response to acetylcholine was augmented and the contraction response to phenylephrine was depressed compared with the proximal artery. In both the proximal and distal mesenteric arteries, acetylcholine-induced relaxations attributable to EDHF were near completely blocked by 18alpha-GA and carbenoxolone to the same degree. Regardless of the presence of L-NAME plus indomethacin, 18alpha-GA significantly augmented the contraction response to phenylephrine.
CONCLUSIONS
The vasomotor regulatory response by EDHF in the rat mesenteric arteries may be explained by extensive heterocellular coupling through MEGJs. Moreover, the release of EDHF through MEGJ may have a essential role in the regulation of resistor arterial tone.

Keyword

connexin; endothelium derived hyperpolarizing factor; gap junction; mesenteric artery

MeSH Terms

Acetylcholine
Animals
Antibodies
Arteries
Carbenoxolone
Connexin 43
Endothelium
Epoprostenol
Gap Junctions*
Humans
Immunohistochemistry
Indomethacin
Male
Mesenteric Arteries
Muscle, Smooth
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Phenylephrine
Rats
Rats, Sprague-Dawley
Relaxation
Acetylcholine
Antibodies
Carbenoxolone
Connexin 43
Epoprostenol
Indomethacin
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Phenylephrine