Evidence for differential roles of nitric oxide (NO) and hyperpolarization in endothelium-dependent relaxation of pig isolated coronary artery

摘要: 1. The possible roles of endothelial and smooth muscle cell hyperpolarization nitric oxide (NO) in endothelium-dependent relaxation were examined isolated rings pig right coronary artery. 2. effects prevented with high K+ (30-125 mM), isotonic Krebs solutions. Functional antagonism due to K(+)-induced contraction was 0.3 microM nifedipine (in all treatments, for consistency). All contracted the thromboxane-mimetic U46619, (1-100 nM) bring them an initial active force within 30-50% maximum contraction. 3. High had no on sensitivity (EC50) or time course (substance P, SP; bradykinin, BK; calcimycin, A23187) -independent (sodium nitroprusside, SNP) agents. Maximum relaxations (Rmax) SP, BK A23187 reduced significantly by approximately 20% but only 125 mM K+. 4. In normal solution (5.9 NG-nitro-L-arginine (L-NOARG; 100 microM) caused 40%, reduction Rmax SNP respectively. EC50s SP decreased two fold whereas that increased ten fold. At concentrations L-NOARG (100 complete inhibition those unaffected. 5. (30 mM) unmasked potent concentration-dependent L-NOARG. 10 L-NOARG, responses abolished at higher (1-10 small significant contractions observed. 6. N0-monomethyl-L-arginine (L-NMMA) similar presence 30 except (40%) achieved MicroM L-NMMA this not either 1000 L-NMMA. K+, (1000 MicroM) EC50 fold, without affecting Rmax.7. choline+ (25, 75 also direct effect SP,but like enabled inhibit these completely. Neither charybdotoxin(30 nor substitution 25 NaCl 50 sucrose any block MicroM).8. conclusion, most if artery vitro is NO, can supplement 60% -80% response NO synthesis blocked. Multiple endothelium-derived factors could explain heterogeneity degree L-arginine analogues, constitute important 'back-up' mechanisms control arterial diameter.