Renin- and non-renin–mediated antihypertensive actions of converting enzyme inhibitors

A 41-year-old black man was admitted to the Massachusetts General Hospital (MGH) because of shortness of breath. The patient had been hypertensive for 10 years. and had been treated with propranolol, 40mg orally three times daily. On the day of admission, he became acutely short of breath, but he denied chest pain and other cardiovascular symptoms. Blood pressure at the time of admission was 200/100 mm Hg. His bean rate was 150 beats/mm, and the electrocardiogram revealed global ST-segment and T-wave changes consistent with diffuse myocardial ischemia. Measurement of blood gases obtained while the patient was breathing room air revealed a Pa02 of 64 mm Hg, PaCO2 of 91 mm Hg. and pH of 7.05. Physical examination disclosed rales in both lung fields to the apices; the chest x-ray revealed bilateral alveolar pulmonary edema. The patient was intubated and given 100% oxygen. His blood pressure fell to 120/70mm Hg and his heart rate decreased to 50 beats/mm. A second electrocardiogram revealed complete heart block and acute right bundle-branch block. Treatment with intravenous epinephrine. atropine, morphine sulfate, and furosemide resulted in an improvement in pulmonary function, resumption of sinus rhythm, and a prompt diuresis. The blood pressure rose to 200/120 mm Hg, and the heart rate increased to 110 beats/mi Funduscopic examination revealed arteriolar narrowing but no hemorrhages or exudates. Examination of the chest revealed normal breath sounds bilaterally; no rales or rhonchi were present. Cardiac examination revealed normal first and second heart sounds; a loud summation gallop was heard, but there were no murmurs, rubs, heaves, or thrills. The point of maximal impulse was palpated in the anterior axillary line, 5th intercostal space. Carotid upstrokes were brisk. Jugular venous pressure was approximately 8 cm of water. Peripheral pulses were full and intact bilaterally. Abdominal examination revealed no organomegaly and no bruits were heard. No evidence of peripheral edema, cyanosis, or clubbing was found. The patient's blood pressure initially was controlled with intravenous nitroprusside. A gradual transition to oral therapy with hydralazine, 50 mg every 6 hours; furosemide, 20 mg twice daily; propranolol, 20 mg every 6 hours; and alpha-methyldopa, 500mg every 6 hours, resulted in a reduction in his blood pressure to 130/90 mm Hg. Prior to discharge from the hospital, urine collection revealed the catecholamine excretion to be within normal limits. A random plasma renin activity was 0.3 ngl mllhr, and the plasma aldosterone concentration was 66 pg/mI. At discharge the patient's BUN was 22 mg/dl. serum creatinine was 2.0 mg/dl, and sodium and potassium concentrations were normal. The patient was returned to the care of his private physician. One month following discharge, the patient's blood pressure was 174/ 112 mm Hg. Hydralazine and alpha-methyldopa administration was discontinued, propranolol was increased to 40 mg every 6 hours, and minoxidil, 5 mg twice daily, was added to his drug regimen. His blood pressure fell to 150/80 mm Hg, and he continued to do well without evidence of congestive heart failure. One year following the initial hospitalization, the patient developed musculoskeletal pain thought to be secondary to degenerative joint disease. He was given indomethacin, 50mg orally three times daily, which relieved his pain. One month later, follow-up examination disclosed a blood pressure of 210/140 mm Hg. The minoxidil dose was raised progressively to 10 mg orally four times daily, but the increase produced no significant effect. Alpha-methyldopa, 500 mg twice daily, was restarted; it also was ineffective. The patient's regimen eventually consisted of minoxidil, 10 mg three times daily; alpha-methyldopa, 500 mg twice daily; furosemide, 40 mg twice daily; captopril, 100 mg three times daily; and propranolol, 40 mg four times daily. On this regimen, the blood pressure remained at 180/110 mm Hg, and the patient returned for further evaluation. He was admitted to the MGH Clinical Research Center and was given a 10 mEq sodium diet. Minoxidil, alpha-methyldopa, captopril. propranolol, and indomethacin were discontinued, but the patient continued to receive 40mg of furosemide daily. Urinary sodium excretion fell to less than 10 mEq/day. The BUN and creatinine concentrations were 14 and 1.1 mg/dl, respectively; serum sodium concentration was 137 mEq/liter, and potassium concentration was 4.4 mEq/Iiter. Plasma renin activity was 0.2 ng/ml/hr in the supine position and 1.1 ng/ml/hr after 3 hours in the upright position. The administration of 75 mg of captopril orally lowered the blood pressure from 160/120mm Hg to 120/90mm Hg