Testosterone-induced relaxation of rat thoracic aorta involves vascular smooth muscle (VSM) K+ channel activation
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Previously, we reported that testosterone (T) produces vasorelaxation oi ihe rat thoracic aorta, which is androgen receptor-independent and involves' both endolhelium-depcndent i nitric oxide) and -independent mechanisms of action. To determine the role of VSM cation channels in the endothelium-mdepcndent effect of T, the contributions of K+ and Ca-+ channels to T-induced vasorclaxalion were examined. Endothelium-dcnuded aortic rings t mm male Spraguc-Dawley rats (12-16 wks age) were prepared fur isometric tension recording (in Krehs-Henseleil-bicarb., 37C 2 50 g passive tension). After equilibration (90 mini, paired aortae were precontracted with phcnylephnne (PE, 1 jjM) and a cumulative dose-response to T (5-300 M) was obtained, in the absence (control, C) or presence of specific K+ channel antagonists. Data are means SE. (n = 4-5 rats per expmtl. group). In C aortae. 'I produced dose-dependent relaxation from 10 M (6 19? of PE contraction) in 300 M (99 0.1 %) Patrealment of aonae with 4-aininopyndine (4-AP, 5 mM) attenuated T-induced relaxation by an average of 40 6 % ( 10-300 M T). In contrast, pretrcatment of aortae wilh either tftraethylainmomuni ( 1 mM) or glibcncl amide ( 10 M) did not alter T-induced relaxation. In a separate group of aortae. contractile responses to Ca2+ (0.1-10 mM) were examined, either alone or in the presence of T or T + 4-AP. Ca2+ alone produced dosc-depcndcnl contraction IVom 0-1 mM (46 1% of 80 mM KC1 contraction) to 10mM(103 1 <) Prelreatment of aortae with T (50 M) attenuated contractile responses to Ca2+ by an average of 56 10 %, whereas pretreatment with T (50 M) + 4-AP (5 mM) only aiienuated contractile responses by an average of 19 4 l/r. These data suggest that the endothelium-indcpendent vasorelaxing effect of T in !he rat aorta involves activation oi oltage-dependent (delayed rectifier) K4 channels and to a lesser extent, inacnvaiion oi oltagc-dependent Ca2+ channels m VSM.