A 52-year-old man presents with a 6-week history of worsening erectile dysfunction despite initiating sildenafil 50 mg daily. His past medical history includes hypertension treated with hydrochlorothiazide 25 mg daily for 3 months prior to sildenafil initiation. Current vital signs: BP 138/88 mmHg, HR 82/min. Laboratory studies show serum potassium 3.2 mEq/L (normal 3.5-5.0), serum magnesium 1.6 mEq/L (normal 1.7-2.2), and fasting glucose 102 mg/dL (previously 95 mg/dL 6 months ago). Physical examination is notable for normal penile sensation, intact bilateral femoral pulses, and no signs of peripheral neuropathy. Which of the following best explains the persistent erectile dysfunction despite sildenafil compliance?

1. A)Sildenafil is directly antagonized by hydrochlorothiazide at the phosphodiesterase-5 enzyme
2. B)Hydrochlorothiazide-induced hypokalemia causes smooth muscle dysfunction that prevents adequate cavernosal relaxation
3. C)Thiazide-induced hyperglycemia and electrolyte depletion impair endothelial nitric oxide production, limiting sildenafil efficacyGABARITO
4. D)The combination creates unopposed alpha-adrenergic activity through sympathetic activation, counteracting vasodilation
5. E)Sildenafil increases urinary potassium excretion, creating a contraindication when combined with potassium-wasting diuretics