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(Circulation Research. 1997;80:1-10.)
© 1997 American Heart Association, Inc.

Articles

Mechanisms of Coronary Microvascular Dilation Induced by the Activation of Pertussis Toxin–Sensitive G Proteins Are Vessel-Size Dependent

Heterogeneous Involvement of Nitric Oxide Pathway and ATP-Sensitive K⁺ Channels

Tatsuya Komaru, Toshinori Tanikawa, Akihiko Sugimura, Toshinobu Kumagai, Kouichi Sato, Hiroshi Kanatsuka, Kunio Shirato

The First Department of Internal Medicine, Tohoku University, School of Medicine, Sendai, Japan.

Correspondence to Tatsuya Komaru, MD, The First Department of Internal Medicine, Tohoku University, School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980 Japan. E-mail komaru@int1.med.tohoku.ac.jp

G proteins are critically important mediators of many signal transduction systems. In the present study, we investigated the effect of direct activation of pertussis toxin (PTX)–sensitive G protein (G_PTX) on coronary arterial microvascular tone in 37 open-chest anesthetized dogs in vivo. Coronary arterial microvessels on the surface of the beating left ventricle were visualized by performing fluorescence coronary microangiography using an intravital microscope with a floating objective system. Microvessels were divided into two groups, small microvessels (inner diameter, 130 µm) and large microvessels (inner diameter, >130 µm). Topically applied mastoparan (G protein activator, 10, 30, and 100 µmol/L) produced homogeneous microvascular dilation in a concentration-dependent manner (10 µmol/L, 7.9±2.0%; 30 µmol/L, 10.3±2.4%; and 100 µmol/L, 16.7±4.5% in small microvessels; 10 µmol/L, 5.3±1.2%; 30 µmol/L, 9.8±2.5%; and 100 µmol/L, 15.5±3.9% in large microvessels). These dilations were reversed to constriction by pretreatment with PTX (300 ng/mL, 2 hours) in both microvessel groups. Blockade of nitric oxide production by N-nitro-L-arginine (LNNA, 300 µmol/L) offset the mastoparan-induced dilation in large microvessels but not in small microvessels. Cosuperfusion of glibenclamide (10 µmol/L) with LNNA produced constriction of all sizes of microvessels in response to mastoparan, whereas charybdotoxin (10 nmol/L) did not affect the mastoparan effect. Pretreatment with glibenclamide alone reversed mastoparan dilation to constriction in small microvessels, whereas it only offset the dilation without producing constriction in large microvessels. We conclude that the activation of G_PTX produces homogeneous coronary arterial microvascular dilation and that the underlining mechanisms of the dilation are vessel size dependent. The L-arginine–nitric oxide pathway mediates the dilation only in large microvessels, whereas ATP-sensitive K⁺ channel activation plays a central role in the dilation of small microvessels when G_PTX is directly activated. ATP-sensitive K⁺ channels are also involved in the dilation of large microvessels in a synergistic fashion with nitric oxide production.

Key Words: coronary circulation • guanine nucleotide regulatory protein • arterioles • microcirculation • vasodilation

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