Testosterone-induced relaxation of rat aorta is androgen structure specific and involves K⁺channel activation

Abstract

Recent studies have established that testosterone (Tes) produces acute (nongenomic) vasorelaxation. This study examined the structural specificity of Tes-induced vasorelaxation and the role of vascular smooth muscle (VSM) K+ channels in rat thoracic aorta. Aortic rings from male Sprague-Dawley rats with (Endo+) and without endothelium (Endo-) were prepared for isometric tension recording. In Endo- aortas precontracted with phenylephrine, 5-300 microM Tes produced dose-dependent relaxation from 10 microM (4 +/- 1%) to 300 microM (100 +/- 1%). In paired Endo+ and Endo- aortas, Tes-induced vasorelaxation was slightly but significantly greater in Endo+ aortas (at 5-150 microM Tes); sensitivity (EC(50)) of the aorta to Tes was reduced by nearly one-half in Endo- vessels. Based on the sensitivity (EC(50)) of Endo- aortas, Tes, the active metabolite 5alpha-dihydrotestosterone, the major excretory metabolites androsterone and etiocholanolone, the nonpolar esters Tes-enanthate and Tes-hemisuccinate (THS), and THS conjugates to BSA (THS-BSA) exhibited relative potencies for vasorelaxation dramatically different from androgen receptor-mediated effects observed in reproductive tissues, with a rank order of THS-BSA > Tes > androsterone = THS = etiocholanolone > dihydrotestosterone >> Tes-enanthate. Pretreatment of aortas with 5 mM 4-aminopyridine attenuated Tes-induced vasorelaxation by an average of 44 +/- 2% (25-300 microM Tes). In contrast, pretreatment of aortas with other K+ channel inhibitors had no effect. These data reveal that Tes-induced vasorelaxation is a structurally specific effect of the androgen molecule, which is enhanced in more polar analogs that have a lower permeability to the VSM cell membrane, and that the effect of Tes involves activation of K+ efflux through K+ channels in VSM, perhaps via the voltage-dependent (delayed-rectifier) K+ channel.

A novel method of seminal vesicle preparation in isolated seminal vesicle experiments in the rat: ring preparation

“…In contrast to studies on the SV, the experiments for hollow organs usually use a ring preparation, for example, studies investigating the effects of sildenafil on human penile blood vessels 12 and testosterone-induced vasodilatory effects of the rat aorta. 17 Similarly, In vitro bath studies could provide more accurate and physiologic results with the ring technique which preserves the natural tubular structure of the SV. In addition, the ring technique demands less manipulation and time to prepare the tissue specimen than the strips; therefore, the ring technique can minimize the hypoxic damage and destruction of the tissue integrity associated with the manipulation of these tissues.…”

Transdermal testosterone gel increases serum testosterone levels in hypogonadal men in Taiwan with improvements in sexual function

“…Further support for these observations came from recent studies on the relationship between testosterone supplementation and erectile dysfunction (ED). [16][17][18][19] Until the last decade such evidence was unclear; the role of androgen supplementation in sexual function was believed to be derived from its effect on sexual interest and libido. 16 Furthermore, experimental animal and human studies have demonstrated that androgens, primarily testosterone, play an important role in the vasculature of the corpus cavernosum of the penis.…”

“…Animal studies in the rat and rabbit have demonstrated a variety of biochemical changes in erectile function and structure that depend on adequate androgen levels. [17][18][19] In humans, the effects of testosterone supplementation have been studied in hypogonadal men with ED. 20 In 15 men with severe hypogonadism and a control group of 20 men with psychogenic ED, testosterone treatment for 6 months with a 5 mg/day patch normalized nocturnal penile tumescence parameters and improved penile vascularization.…”

Combined use of androgen and sildenafil for hypogonadal patients unresponsive to sildenafil alone

“…3,4 Testosterone also has a permissive role in erectile function, which is not exclusively NO-dependent and induces acute (nongenomic) vasorelaxation via K þ channel activation of vascular smooth muscle cells. 5 Castration, besides leading to reduced NOS expression, also appeared to modify phosphodiesterase type-5 (PDE-5) gene expression in a rabbit model. 6,7 Recent evidence suggests that androgens may directly control the expression and activity of PDE-5 in the human corpus cavernosum.…”