A 52-year-old man with hypertension is started on atenolol 50 mg daily. After 2 weeks, his blood pressure remains 155/95 mmHg despite good adherence. The physician increases the dose to 100 mg daily. After another 2 weeks, there is minimal further reduction in blood pressure. A repeat dose escalation to 150 mg daily produces no additional benefit. Which pharmacodynamic principle best explains the plateau in blood pressure reduction despite increasing atenolol doses?