Hypotensive Effect of β-Adrenoceptor Blockers

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Pronethalol was the first beta adrenoceptor blocking drug to be used in the treatment of hypertension (Prichard 1964), Pronethalol was withdrawn because of its tumour-producing action in mice (Paget 1963), but the use of propranolol in hypertension was reported soon after (Prichard and Gillam 1964). These drugs were only slowly accepted in the treatment of hypertension. This was possibly because beta receptor antagonists inhibit cardiac contraction and this was considered to be an undesirable effect. The consequent increase in peripheral resistance from acute beta- adrenergic blockade from propranolol also seemed disadvantageous. Additionally, the antihypertensive effect had not been described in animals, and the mechanism of this action was unknown. Another reason for this slow acceptance of beta-adrenergic blockade was the use of inadequate doses, so that the full hypotensive effect was often delayed. Early investigators tended to fix doses at suboptimal levels, despite original reports (Prichard and Gillam 1964,1966) emphasizing the importance of variable dosage regimens. The misgivings about dosage arose from erroneous concepts of complete beta adrenoceptor blockade. A relatively small dose of propranolol had been observed to block the effect of isoprenaline, which had previously caused a maximal tachycardia. Considerably larger doses are needed to produce maximum inhibition of exercise-induced tachycardia or even the supine or standing resting heart rate (Boakes et al. 1973), and the same is true for other beta-adrenergic blocking drugs, such as oxprenolol (Taylor and Meeran 1973a).