EFFECTS OF ACETYLCHOLINE ON DIFFERENT MUSCARINIC RECEPTORS IN THE PERFUSED PORCINE EAR VEIN

Study objective - Acetylcholine (ACh) induced vasomotion was studied in the venous vessel wall of the pig. Experimental material - Fresh porcine ear veins were prepared, cannulated, and perfused in organ chambers. ACh was either applied intraluminally via the perfusion fluid or extraluminally via the organ bath solution. Measurements and main results - The porcine ear vein showed three different concentration dependent vasomotions. ACh at a concentration of more than 10(-9) M caused a relaxation which was inhibited by atropine (10(-6) M) or by intraluminal perfusion with distilled water for 5 min. Gallamine (10(-5) M), pirenzepine (3.10(-7) M), indomethacin (10(-5) M), and the Ca blockers verapamil (10(-6) M) and nimodipine (10(-6) M) did not interfere with the relaxation. At an intraluminal concentration of more than 10(-7) M the ACh induced relaxation was immediately followed by a tachyphylactic contraction; this contraction was blocked by atropine, pirenzepine, intraluminal perfusion with distilled water, indomethacin, and the Ca blockers verapamil and nimodipine. After an initial ACh application of 10(-5) M (intra- or extraluminal) 50% of the veins contracted strongly and reproducibly; this contraction was attenuated by atropine and pirenzepine but was unaffected by distilled water, gallamine or indomethacin. Intraluminal ACh evoked significantly higher dilating and tachphylactic contractile responses compared to extraluminal ACh, indicating that the receptors for these vasomotions were located at the luminal site of the vessel. Nicotine had no effect on the vein. Conclusions - In the porcine ear vein ACh evokes three different kinds of muscarinic vasomotions. These are mediated by different receptors with different sensitivities and localised on various sites in the vessel wall. Negative feedback mechanisms may exist between them.