A 52-year-old man with hypertension is started on atenolol 50 mg daily. After 2 weeks, his blood pressure remains elevated at 160/95 mmHg despite good adherence. His heart rate is 58 bpm. The physician increases the dose to 100 mg daily. After another 2 weeks, the blood pressure is still 155/92 mmHg, and heart rate is now 52 bpm. Which pharmacodynamic principle best explains the lack of further blood pressure reduction despite dose escalation and increased heart rate reduction?