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(ω)-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.
- coronary circulation
- guanine nucleotide regulatory protein
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine