ACETYLCHOLINE-INDUCED ENDOTHELIUM-INDEPENDENT RELAXATIONS IN MONKEY ISOLATED SUPERIOR AND INFERIOR CAVAL VEINS

1 We examined the effects of acetylcholine (ACh), isoprenaline (Isop) and Ca-ionophore, A23187 on monkey isolated superior (SCV) and inferio r caval veins (ICV) with and without intact endothelium, which had bee n partially contracted by 2 x 10(-6) - 5 X 10(-6) M prostaglandin F2al pha (PGF2alpha). 2 Low concentrations of ACh (10(-10) - 10(-9) m) prod uced a dose-dependent relaxation in the precontracted venous segments with endothelium. ACh at concentrations more than 10(-7) M elicited a transient contraction followed by a relaxation in these segments. 3 An addition of 5 x 10(-7) M A23187 induced about 60% of maximum relaxati on produced by 10(-5) M sodium nitroprusside (SNP) in each venous segm ent with endothelium. 4 Isop (10(-10) - 10(-5) M) caused a dose-relate d relaxation in the precontracted caval veins with intact endothelium. 5 Removal of endothelium caused no significant effect on the ACh-indu ced dual responses but a significant inhibition of the A23187-induced relaxation. 6 Pretreatment with atropine antagonized competitively the ACh-induced relaxations in the endothelium-intact and endothelium-den uded caval veins. The Schild plot analysis showed that the pA2 values of the segments with and without endothelium were 9.72 +/- 0.14 (n = 5 ) and 10.01 +/- 0.23 (n = 6) in the ICV; and 9.95 +/- 0.20 (n = 5) and 9.70 +/- 0. 10 (n = 5) in the SCV, respectively. 7 Pretreatment with 5 x 10(-5) M aspirin, 3 x 10(-5) M N(G)-nitro-L-arginine methylester, 1 mM tetraethylammonium, or 3 x 10(-6) M glibenclamide caused no signi ficant effect on the basal tone, ACh-induced transient contraction, an d ACh-induced relaxation in the precontracted venous segments with and without endothelium. 8 Pretreatment with 10(-5) M methylene blue prod uced a significant reduction of the ACh- and SNP-induced relaxations i n the precontracted venous segments with and without endothelium. The pretreatment with the same concentration of methylene blue, however, c aused no significant effect on the Isop-induced relaxation in venous s egments with endothelium. 9 The results suggest that ACh acts directly on the venous smooth muscle cells via a high-affinity muscarinic rece ptor subtype to accumulate cellular cyclic GMP producing endothelium-i ndependent relaxation in the monkey caval veins.