Several recent studies have demonstrated that estrogen produces rapid (nongenomic) vasorelaxation; however, little is known about the direct effects of testosterone (T) on vascular smooth muscle. Therefore, we examined acute effects of T on contractile responses and K+ channel activity in coronary arteries. Left anterior descending coronary arteries were dissected from porcine hearts, and paired rings (2 mm) were prepared for isometric tension recording (Krebs-Henseleit soln., 37C, 2.50g passive tension). After equilibration (90 min), vessels were precontracted with PGF2a (10M) to a stable plateau tension, and a cumulative concentration-response to T or T-vehicle was obtained (5-50M). T elicited a maximal relaxation of >80% at 25M. In contrast, arteries contracted with 80mM KCl relaxed only 12% (n=8) to T, suggesting involvement of K+ channels. Cell-attached patch-clamp studies were then performed on coronary myocytes to determine the potential role of K+ channels in T-induced relaxation. Single-channel activity was dominated by a large-conductance (11914pS), calcium- and TEA (1mM)-sensitive potassium (BKCa) channel. T increased BKCa channel activity (NPo at +40mV) from 0 to 0.3 (n=3) after 30 minutes. This stimulatory effect was inhibited >80% (n=3) by 400M aminoguanidine or 20M L-NAME, inhibitors of nitric oxide synthase activity. These data suggest that T has a direct vasorelaxing effect on porcine coronary arteries which may involve stimulation of BKCa channel activity via nitric oxide.
