INHIBITION OF CAMP-MEDIATED RELAXATION IN RAT CORONARY VESSELS BY BLOCK OF CA2+ ACTIVATED K+ CHANNELS

The hypothesis for this study is that block of calcium activated potas sium (K-Ca) channels inhibits cAMP induced relaxation in pressurized r at coronary resistance arteries. Pressure-diameter experiments with se ptal arteries (200-270 mu m internal diameter at 60 mmHg and maximum d ilation) showed significant basal tone over a range of pressure from 4 0-120 mmHg. The level of tone was increased with the thromboxane A(2) analogue 9,11-dideoxy-11 alpha, 9 alpha-epoxy-methanoprostaglandin F-2 alpha (U46619) in all experiments. Receptor activation of the cAMP pa thway was done with adenosine (ADO) and isoproterenol (ISO). Tetraethy lammonium ion (TEA(+)), 1 mM, significantly inhibited relaxation to AD O (10(-6)-10(-3) M) with a maximal inhibition of 75 +/- 7% (as a % of maximum diameter change with the vasodilator alone) at 10(-3) M ADO. T EA(+) inhibited ISO (10(-6) M) relaxation by 63 +/- 9%. Direct activat ion of the cAMP pathway was done with forskolin and 8-bromo-cAMP. TEA( +) significantly inhibited forskolin (20(-6)-10(-4) M) induced relaxat ion with a maximal inhibition of 81.3 +/- 1.2% at 10(-4) M forskolin. TEA(+) and iberiotoxin (10(-7) M) significantly inhibited 8-bromo-cAMP (10(-3) M) induced relaxation by 72 +/- 5% and 56 +/- 3% respectively . The effect of TEA(+) on relaxation induced by nitroprusside (a cGMP dependent vasodilator) was not significant. The results show that rat coronary resistance arteries possess significant myogenic tone and mod ulation of K-Ca channels plays a major role in cAMP mediated relaxatio n.