Expression of cyclic AMP-dependent protein kinase isoforms in human cavernous arteries: functional significance and relation to phosphodiesterase type 4.

INTRODUCTION: The cyclic adenosine monophosphate-dependent protein kinase (cAK) is considered a key protein in the control of smooth muscle tone in the cardiovascular system. There is evidence that erectile dysfunction might be linked to systemic vascular disorders and arterial insufficiency, subsequently resulting in structural changes in the penile tissue. The expression and significance of cAK in human cavernous arteries (HCA) have not been evaluated. AIMS: To evaluate the expression of cAK isoforms in HCA and examine the role of cAK in the cyclic adenosine monophosphate (cAMP)- and cyclic guanosine monophosphate (cGMP)-mediated control of penile vascular smooth muscle. METHODS: The expression and distribution of phosphodiesterase type 4 (PDE4) and cAK isoforms in sections of HCA were investigated by means of immunohistochemistry and Western blot analysis. The effects of the cAK inhibitor Rp-8-CPT-cAMPS on the relaxation of isolated preparations of HCA (diameter > 100 µm) induced by rolipram, sildenafil, tadalafil, and vardenafil were studied using the organ bath technique. MAIN OUTCOME MEASURES: Investigate the expression of cAK in relation to α-actin and PDE4 in HCA and evaluate the effects of an inhibition of cAK on the relaxation induced by inhibitors of PDE4 and PDE5 of isolated penile arteries. RESULTS: Immunosignals specific for cAKIα, IIα, and IIß were observed within the wall of HCA. Double stainings revealed colocalization of cAK with α-actin and PDE4. The expression of cAK isoforms was confirmed by Western blot analysis. The reversion of tension induced by inhibitors of PDE4 and PDE5 of isolated penile vascular tissue were attenuated significantly by Rp-8-CPT-cAMPS. CONCLUSIONS: Our results demonstrate the expression of cAK isoforms in the smooth musculature of HCA and its colocalization with PDE4. A significant role for cAK in the regulation mediated by cAMP and cGMP of vascular smooth muscle tone in HCA can also be assumed.

Non-genomic effects of androgens on isolated human vascular and nonvascular penile erectile tissue.

OBJECTIVES: To evaluate non-genomic effects of testosterone and dihydrotestosterone (DHT) on isolated human cavernosal arteries (HCA) and corpus cavernosum (HCC) using organ-bath studies and radio-immunoassays (RIA), as non-genomic effects of androgens are reported for vascular smooth musculature and there is evidence that the relaxant response involves a modulation of cyclic nucleotide tissue levels. MATERIALS AND METHODS: The relaxation induced by the cumulative addition of testosterone and DHT (0.01-10 microm) was studied using circular segments of HCA and strip preparations of HCC. To evaluate the effects of testosterone and DHT on tissue levels of cAMP and cGMP, specimens were exposed to increasing concentrations of the hormones. Forskolin and sodium nitroprusside (SNP) served as reference compounds. RESULTS: Testosterone and DHT dose-dependently reversed the noradrenaline-induced tension of vascular segments and HCC strips. At the maximum concentration, testosterone and DHT reduced the mean (sd) tension to 79.8 (4.43)% and 83.9 (10.94)%, respectively. SNP and forskolin significantly stimulated the production of cGMP and cAMP. No effects of testosterone and DHT on cGMP and cAMP levels were detected. CONCLUSION: Rapid androgen-induced relaxation of HCA and HCC occurs via non-genomic mechanisms. In penile erectile tissue, non-genomic relaxant effects of testosterone and DHT are not mediated via modulation of cyclic nucleotide tissue levels. Additional studies are required to establish if non-genomic relaxant effects are important in ensuring a basal level of perfusion to maintain overall penile function.

Catheter-assisted vein sclerotherapy: a new approach for sclerotherapy of the greater saphenous vein with a double-lumen balloon catheter.

OBJECTIVE: We sought to optimize sclerotherapy of the greater saphenous vein (GSV) by targeted application of foamed sclerosant by using a catheter. METHODS: We designed a new double-lumen catheter that is inserted into the GSV. Via one lumen, a balloon at the tip of the catheter can be inflated to stop the blood flow. Via the second lumen, the sclerosing agent can be injected and aspirated. This method enabled us to perform a targeted application of the sclerosing agent [catheter-assisted vein sclerotherapy (KAVS)]. In an open study, outpatients suffering from varicosis of the GSV received a foam sclerotherapy under ultrasound guidance, using the newly developed KAVS catheter. RESULTS: Thirty patients with an insufficiency (reflux) of the GSV were treated with the newly developed KAVS method using foamed polidocanol. The intervention was well tolerated in all patients without the occurrence of serious side effects. In 27 of the 30 treated patients (90%), we found a closure of the GSV at control visits 6 weeks, 3 months, and 6 months after treatment. CONCLUSIONS: The KAVS method represents a feasible approach for sclerotherapy of the GSV. The efficiency and treatment modalities need to be explored in further studies.