This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 89/8/716    most recent hh2001.097783v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Véquaud, P. Articles by Thorin, E. Search for Related Content PubMed PubMed Citation Articles by Véquaud, P. Articles by Thorin, E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL NITRIC OXIDE Related Collections Cardiovascular Pharmacology Cell signalling/signal transduction Endothelium/vascular type/nitric oxide

(Circulation Research. 2001;89:716.)
© 2001 American Heart Association, Inc.

Integrative Physiology

Endothelial G Protein ß-Subunits Trigger Nitric Oxide– but not Endothelium-Derived Hyperpolarizing Factor–Dependent Dilation in Rabbit Resistance Arteries

Philippe Véquaud, Eric Thorin

From the Institut de Cardiologie de Montréal, Centre de Recherche, Montréal, Québec, Canada.

Correspondence to Dr Eric Thorin, Institut de Cardiologie de Montréal, Centre de Recherche, 5000 rue Bélanger Est, Montréal H1T 1C8, Québec, Canada. E-mail thorin{at}icm.umontreal.ca

Abstract—— A single subtype of heterotrimeric G protein–coupled receptor controls both nitric oxide (NO) (sensitive to L-arginine analogues) and endothelium-derived hyperpolarizing factor (EDHF) (sensitive to high-external K⁺ and apamine) production by the vascular endothelium leading to dilation. We hypothesized that - and ß-subunits of the G protein serve as distinct intermediates to produce NO and EDHF. In pressurized resistance arteries, selective pinocytotic endothelial incorporation of specific antibodies (Abs) directed against _q/11-subunits abolished acetylcholine (Ach)-mediated dilation but failed to influence oxymetazoline (Oxy, ₂-adrenergic receptor agonist)-induced dilation. In contrast, _i1-2-subunit Abs prevented Oxy- but not Ach-induced dilation. Thus, as expected, endothelial muscarinic and ₂-adrenoceptors couple to G_q protein and G_i proteins, respectively. ß-subunit Abs reduced both Ach- and Oxy-induced dilation. The ß-subunit Abs abolished the nitro-L-arginine (L-NNA)-sensitive component but did not impair the high-external K⁺-sensitive component of the dilation induced by Ach and Oxy. Thus, G protein ß-subunits primarily accounted for NO production. Neutralization of Hsp90 and inhibition of the phospholipase C by U73122 (1 µmol/L) or intracellular Ca²⁺ buffering with BAPTA-AM (10 µmol/L) sharply reduced NO-dependent but not K⁺-sensitive dilation. In conclusion, mobilization of the G protein ß-subunit is pivotal to NO-dependent dilation triggered through muscarinic and ₂-adrenergic receptors. In contrast, receptor-operated EDHF-dependent dilation was insensitive to ß-subunit Abs. Although not directly activating the NO pathway, -subunit activation is an absolute prerequisite for receptor-operated endothelium-dependent dilation of resistance arteries.

Key Words: G protein subunits • endothelium • nitric oxide • endothelium-derived hyperpolarizing factor • dilation

This article has been cited by other articles:

				E. Thorin and N. Thorin-Trescases Vascular endothelial ageing, heartbeat after heartbeat Cardiovasc Res, October 1, 2009; 84(1): 24 - 32. [Abstract] [Full Text] [PDF]

				R. Koshida, P. Rocic, S. Saito, T. Kiyooka, C. Zhang, and W. M. Chilian Role of Focal Adhesion Kinase in Flow-Induced Dilation of Coronary Arterioles Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2548 - 2553. [Abstract] [Full Text] [PDF]

				S. Mather, K. A. Dora, S. L. Sandow, P. Winter, and C. J. Garland Rapid Endothelial Cell-Selective Loading of Connexin 40 Antibody Blocks Endothelium-Derived Hyperpolarizing Factor Dilation in Rat Small Mesenteric Arteries Circ. Res., August 19, 2005; 97(4): 399 - 407. [Abstract] [Full Text] [PDF]

				S. Budel, I. S. Bartlett, and S. S. Segal Homocellular Conduction Along Endothelium and Smooth Muscle of Arterioles in Hamster Cheek Pouch: Unmasking an NO Wave Circ. Res., July 11, 2003; 93(1): 61 - 68. [Abstract] [Full Text] [PDF]

				W. M. Chilian and R. Koshida EDHF and NO: Different Pathways for Production--Similar Actions Circ. Res., October 12, 2001; 89(8): 648 - 649. [Full Text] [PDF]