Ca 2-antagonists reveal a novel inhibitory activity of caerulein on guinea pig ileum

Abstract

To study the influence of alpha-adrenergic stimuli on non-adrenergic non-cholinergic (NANC) neurogenic relaxation in isolated horse penile resistance arteries.Deep intracavernous penile arteries with an internal lumen diameter of 200-500 micro m., isolated from the corpus cavernosum of young horses, were mounted in microvascular myographs for isometric tension recording and electrical field stimulation (EFS) of autonomic nerve terminals.In the presence of guanethidine (10 sup -5 M) and atropine (10 sup -7 M) tone of the arteries was raised by the thromboxane analogue, U46619. EFS (1, 4 and 32 Hz) induced frequency-dependent relaxations, which were abolished in the presence of tetrodotoxin, while NG-nitro-L-arginine (L-NOARG, 10 sup -4 M) abolished the relaxations to EFS at 1 Hz, and significantly reduced the relaxations at 4 Hz and 32 Hz by 82.5 +/- 10.2% and 52.9 +/- 4.7%, respectively (n = 6). EFS induced relaxations of a similar magnitude in penile arteries contracted with U46619 or the alpha1-adrenoceptor agonist, phenylephrine, while the alpha2-adrenoceptor agonist, BHT920 (10 sup -6 M), produced an inhibitory effect on the EFS-evoked relaxations which was inversely related to the stimulus frequency (1, 4 and 32 Hz). BHT920 had no effect on the relaxations induced by exogenous nitric oxide (NO), added as acidified sodium nitrite (10 sup -6-10 sup -3 M). The inhibitory effect of BHT920 on NANC relaxations was reversed by 10 sup -7 M rauwolscine.These results suggest that the release of a NANC neurotransmitter primarily thought to be NO is inhibited by stimulation of prejunctional alpha2-adrenoceptors in horse penile resistance arteries.