Treatment of hypertension with beta-blockers with and without intrinsic sympathomimetic activity

In a randomized double-blind trial 36 patients with essential hypertension were treated with either metoprolol or pindolol for 6 months following a 6-week placebo period. At the end of the placebo period and after 6 weeks and 6 months of active therapy peripheral hemodynamics at rest and during maximal vasodilatation were studied. Exercise heart rate was reduced to the same extent with both metoprolol and pindolol, indicating that the doses used (metoprolol average 179 mg/day; pindolol average 12 mg/day) were equipotent as regards beta-adrenoceptor blocking effect. The antihypertensive effect was identical with both compounds. However, metoprolol caused a significant reduction of heart rate at rest both at 6 weeks and 6 months. With pindolol the reduction in heart rate was not significant at 6 weeks, and it was clearly much less than with metoprolol. On the other hand, no change in calf vascular resistance was seen during metoprolol therapy, whereas a marked and statistically significant reduction was caused by pindolol. Resistance at maximal dilatation in the forearm did not change with metoprolol, but tended to fall with pindolol after 6 weeks and was significantly reduced after 6 months. This indicates that although metoprolol and pindolol have the same antihypertensive potency, the two agents appear to reduce blood pressure through different mechanisms. Thus, cardiac mechanisms seem to play the most important role with metoprolol, whereas pindolol mainly acts by a reduction in vascular resistance. It also seems that treatment with pindolol normalizes the structural arteriolar abnormality present in hypertension as indicated by the reduction in resistance at maximal vasodilation.