Relationship of plasma catecholamines to blood pressure in hypertensive patients during beta‐adrenoceptor blockade with and without intrinsic sympathomimetic activity.

Abstract

1 This study was designed to follow changes in plasma catecholamine concentrations during ,B-adrenoceptor blockade using doses of antagonists which decreased the mean arterial pressure (MAP) by about 15 mm Hg. Noradrenaline, adrenaline and dopamine were radioenzymatically determined in 34 patients with moderate essential hypertension during an 8 week course of treatment with either pindolol (with intrinsic sympathomimetic activity, ISA) or propranolol (without ISA). Plasma catecholamines were determined before and 1, 7, 28 and 56 days after commencement of treatment and 1 week after discontinuation of treatment. 2 After one day of pindolol therapy plasma catecholamine concentrations were decreased, but no decrease in MAP was observed. After one day of propranolol therapy, however, MAP was decreased, but except for increased levels of adrenaline, plasma catecholamines showed no changes. 3 On the 56th day of therapy both 0-adrenoceptor blockers had decreased the MAP. Pindolol therapy had caused a decrease in all three catecholamines whereas propranolol had caused no change except for decreased dopamine levels. 4 One week after cessation of propranolol therapy catecholamines were decreased but the MAP had begun to return to initial values; after cessation of pindolol therapy however, the MAP remained decreased. 5 The dissimilar relationships between blood pressure and catecholamine concentration during pindolol and propranolol therapy are evidence for multiple and different modes of action for P-adrenoceptor blockers with and without ISA. This study demonstrates that catecholamine concentrations were generally decreased during low-dose P-adrenoceptor blocker therapy, with lower catecholamine levels during pindolol treatment than during propranolol treatment.

Plasma catecholamines following exercise in hypertensives treated with pindolol: comparison with placebo and metoprolol.

“…The levels of noradrenaline reached following exercise in the pre-treatment period were similar to those reported by us during placebo treatment. In the same study (Kirsten et al, 1982) comparison with pre-treatment values showed that postexercise noradrenaline was lower following 8 weeks treatment with pindolol. At this time, noradrenaline concentration was significantly lower during pindolol than during propranolol treatment, analogous to the findings reported here between pindolol and metoprolol after 3 weeks treatment.…”

“…The difficulties introduced by inadequate controls were also demonstrated in a recent study (Kirsten et al, 1982) where plasma noradrenaline following bicycle exercise was found to be lower after 4 weeks propranolol treatment, compared with pre-treatment levels. The levels of noradrenaline reached following exercise in the pre-treatment period were similar to those reported by us during placebo treatment.…”

“…However, studies claiming to show a fall in plasma noradrenaline with pindolol were either inadequately controlled or based on comparisons with 1-adrenoceptor blockers without ISA (Franz et al, 1980;Kirsten et al, 1982). This study using a randomised, cross-over and placebo controlled design, was carried out to examine this question and provide information on changes in plasma adrenaline which are poorly documented.…”

“…The finding of an apparent reduction in plasma noradrenaline following chronic treatment with pindolol (Kirsten etal., 1982) was used as evidence in support of the hypothesis that blockade of prejunctional 3-adrenoceptors is responsible for the hypotensive action of 3-adrenoceptor blockers (Man in' T Veld & Schalekamp, 1982). However, studies claiming to show a fall in plasma noradrenaline with pindolol were either inadequately controlled or based on comparisons with 1-adrenoceptor blockers without ISA (Franz et al, 1980;Kirsten et al, 1982). This study using a randomised, cross-over and placebo controlled design, was carried out to examine this question and provide information on changes in plasma adrenaline which are poorly documented.…”