The key findings of this study are (1) despite morbid obesity, rats lacking MC4R receptors are not hypertensive, (2) despite obesity and severe insulin resistance, rats lacking MC4R show no deficits in endothelial dysfunction, and (3) deletion of MC4R produced a significant bradycardia and increased sympathetic tone to the vasculature. The gene discussed is MC4R; the disease is obesity due to melanocortin 4 receptor deficiency.