The Adrenomedullary Venous Vasculature as a Target for Endothelins: Comparison of the Porcine and Bovine Central Adrenomedullary Veins

Abstract

The functional properties of the isolated porcine and bovine central adrenomedullary veins were compared, with emphasis on the active tension responses to high K +, endothelin-1 (ET-1) and neuropeptide Y (NPY). In the porcine vein, the contraction evoked by ET-1 was 4–5-fold higher than with high K +, as in the bovine vein. The potencies for ET-1 were similar in ring and strip preparations of the porcine vein, with EC 50 values 5–7-fold higher than in the bovine vein. In preparations previously exposed to ET-1 the contractions evoked by high K + and NPY were potentiated and facilitated, respectively,. However, only in the porcine vein was the ET-1 contraction sustained. This contraction was effectively relaxed by milrinone, indicating a role for cGMP inhibited cyclic nucleotide phosphodiesterase in the sustained contraction. Caffeine and forskolin were also effective relaxants of contractions evoked by ET-1 in both veins, suggesting relaxation by elevated levels of cAMP. The K +-contracted porcine, but not bovine, vein was relaxed by acetylcholine (ACh) and vasointestinal polypeptide in a concentration-dependent manner, indicating species differences with respect to signal transduction leading to increases in cyclic nucleotides. In conclusion, these results demonstrate that ET-1 is the main constrictor of the porcine central adrenomedullary vein, with significant species differences in mode of contraction and relaxation. These findings suggest roles for the endogenously released ET-1 and NPY in regulation of venous contractility within the adrenal gland of mammals.