No abstract

Eight patients taking metoprolol (300 mg/day) for essential hypertension were studied after abrupt withdrawal and placebo replacement of the drug. A 52% average rebound increase in cardiac chronotropic sensitivity to isoproterenol and 15% rebound rise in resting heart rate occurred in all patients between 2 to 8 days after metoprolol withdrawal (P less than 0.05). Holter monitoring showed no associated arrhythmia. A transient increase in blood pressure occurred in one patient and withdrawal-like symptoms were noted in three patients. There were no meaningful changes in plasma norepinephrine, epinephrine, thyroxine, or triiodothyronine. Seven of the eight patients were again studied serially after the same metoprolol dosing, during a prolonged low-dose withdrawal schedule (50 mg/day for 10 days) and during placebo. Prolonged low dose before complete metoprolol withdrawal decreased but did not completely prevent the changes observed after abrupt withdrawal. The observed rebound of cardiac beta-adrenergic sensitivity may have application to the mechanism and prevention of the beta-blocker syndrome in patients with angina.

No abstract

Factors determining vascular resistance were examined in 6 normotensive subjects (NT), 5 with established hypertension (EH) and diastolic pressures greater than 90 mmHg and 7 with borderline hypertension (BH) having pressures intermittently greater than 140/90 mmHg. Using plethysmography, we measured forearm blood flow (FBF), arterial resistance (FAR) and venous compliance (FVC) before and after autonomic blockade with propranolol 0.2 mg/kh, atropine 0.04 mg/kg and phentolamine 15 mg I.V. Subjects with EH had the highest baseline FBF. MAP was increased 18-22% after atropine and propranolol in all 3 groups. Phentolamine decreased MAP -8.9 +/- 2.1% in NT, -6.9 +/-1.2% in BH and -16.5 +/- 1.9% in EH (p less than 0.05). After total blockade, FAR in EH (32.4 +/- 4.8 units) was similar to FAR in TN (31.0 +/- 3.6 units) whereas that in BH remained high (50.2 +/- 3.8 units; p less than 0.01). Baseline FVC was highest in NT, intermediate in BH and lowest in EH and was not altered by autonomic blockade. Non-gravitational exercise for 6 min during upper arm arterial occlusion after autonomic blockade resulted in a residual FAR of 2.3 +/- 0.1 units in NT, 3.8 +/- 0.3 units in BH and 4.2 +/- 1.7 units in EH (p less than 0.01) during reactive hyperemia. Increased FAR in our subjects with BH and EH was probably due to structural vascular alterations. The greater increase in FAR and MAP in EH over that observed in BH has a sympathetic nervous system component.