title: Acetylcholine-induced endothelium-independent relaxations in monkey isolated superior and inferior caval veins.
abstract: 1. We examined the effects of acetylcholine (ACh), isoprenaline (Isop) and Ca-ionophore, A23187 on monkey isolated superior (SCV) and inferior caval veins (ICV) with and without intact endothelium, which had been partially contracted by 2 x 10(-6)-5 x 10(-6) M prostaglandin F2 alpha (PGF2 alpha). 2. Low concentrations of ACh (10(-10)-10(-9) M) produced 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 A 23187 induced about 60% of maximum relaxation produced by 10(-5) M sodium nitroprusside (SNP) in each venous segment with endothelium. 4. Isop (10(-10)-10(-5) M) caused a dose-related relaxation in the precontracted caval veins with intact endothelium. 5. Removal of endothelium caused no significant effect on the ACh-induced 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-denuded 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 10-5M aspirin, 3 x 10-5M N0-nitro-L-arginine methylester, 1 mM tetraethylammonium,or 3 x 10-6 M glibenclamide caused no significant effect on the basal tone, ACh induced transient contraction, and ACh;.induced relaxation in the precontracted venous segments with and without endothelium.8. Pretreatment with 10-5 M methylene blue produced a significant reduction of the ACh- and SNP induced relaxations in the precontracted venous segments with and without endothelium. The pretreatment with the same concentration of methylene blue, however, caused no significant effect on the Isop-induced relaxation in venous segments with endothelium.9. The results suggest that ACh acts directly on the venous smooth muscle cells via a high-affinity muscarinic receptor subtype to accumulate cellular cyclic GMP producing endothelium-independent relaxation in the monkey caval veins.
authors.affiliation: 1st Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fukushima
authors.forename: T
authors.initials: T
authors.lastname: Ohhashi
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008251:Macaca; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D009599:Nitroprusside / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014682:Vena Cava, Inferior / Q000187:drug effects*; D014683:Vena Cava, Superior / Q000187:drug effects*
chemical_list: D013757:Tetraethylammonium Compounds; D009599:Nitroprusside; D000001:Calcimycin; D001120:Arginine; D015237:Dinoprost; D007545:Isoproterenol; D000109:Acetylcholine; D001241:Aspirin; D005905:Glyburide; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester