Mode of action of β–adrenoceptor blocking agents in hypertension. A comparison between metoprolol and pindolol with special reference to peripheral vascular effects

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Abstract
Beta-Adrenoceptor blocking drugs are generally recognized as being effective in the treatment of hypertension. The mechanisms whereby these drugs reduce blood pressure are, however, not fully understood. In a double-blind, randomized study either metoprolol, 100--300 mg/day, or pindolol, 5--15 mg/day, was given for 6 months and the effects on blood pressure, heart rate and vascular resistance in the calf and forearm were investigated. Measurements were made at rest, during and after physical exercise, and during postischaemic hyperaemia. Both drugs reduced blood pressure to the same extent both at rest and during and after exercise. Metoprolol reduced heart rate to a greater extent than pindolol at rest and after exercise, whereas no difference was seen during physical exercise. Pindolol reduced the vascular resistance in the calf at rest by 14% (p less than 0.05), whereas metoprolol tended to increase vascular resistance, the difference in effect being highly significant (p less than 0.005). During and after leg exercise, there was no difference in forearm vascular resistance between the two drugs. It may be concluded that pindolol reduced resting blood pressure partly through peripheral vasodilatation. This was probably an effect of beta 2-adrenoceptor stimulation linked to the pronounced intrinsic sympathomimetic activity (ISA) of pindolol. Metoprolol on the other hand, acted mainly through cardiac mechanisms, as suggested by its pronounced reduction of heart rate.