Atenolol-Induced Regulation of Leukocyte β₂-Adrenoceptors in Hypertension

Abstract

β₂-Adrenoceptor characteristics of human mononuclear leukocytes were assayed in hypertensive patients before and after treatment with 100 mg/day atenolol. While no changes have been observed in receptor affinity, a statistically significant increase (36%) has been demonstrated in receptor density following treatment. Blood pressure and heart rate were also measured in order to test the efficacy of the administered drug. All these parameters showed a fall in the post-treatment values. It is concluded that at therapeutic concentration, β₂-adrenoceptors undergo up-regulation by atenolol in spite of its cardioselectivity. Such a regulation, which may represent a fundamental step in the mechanism leading to withdrawal syndrome, may, therefore, be suggested being quite widespread.

Acebutolol-Induced Decrease of Mononuclear Leukocyte β-Adrenoceptors in Hypertension

“…The same parallelism adds new support to the hypothesis that human MNL may be used as a tool to estimate receptor character istics of other human tissues which cannot be studied directly [8][9][10]15]. Present findings on the regulation of receptors by drugs with ISA may also be useful in the development of the pharmacological research strategics in this area.…”

“…Clinical signs of a with drawal syndrome were demonstrated with the nonselective blocker propranolol [ I ] as well as with the cardioselective ones atenolol [3] and meioprolol [4], Parallclly, up-regulation of [3-adrcnoceptors was observed both after the administration of propranolol in rat heart [5] and brain [6] and in human lymphocytes [7] and after atenolol treatment in human MNL [8], In contrast, the present findings demon strate a small decrease in MNL receptor den sity from patients treated with the partial ago nist acébutolol. Very interestingly, no signs of withdrawal syndrome were observed in sub jects treated with the (3-blocker oxprenolol.…”

“…The method has already been used in assays of P-adrenoceptors from either mouse subman dibular glands [13] or human MNL [8,10).…”

“…6], and human lymphocytes [7] after sudden interruption of therapy with the nonselective blocker propranolol. Recently, it has been demonstrated that P-adrenoceptors of human mononuclear leukocytes (MNL) undergo up-regulation by atenolol, in spite of its cardioselectivity, when given to hyper tensive patients at therapeutic concentra tions [8).…”

Beta-adrenergic signalling and threshhold adrenaline concentration for induction of fibrillation in the perfused heart pretreated with antihypertensive drugs

“…This is in line with clinical studies showing that some 20% of hypokalemic patients admitted to hospital for coronary infarction showed malignant arrhythmias [17]. This may be due to the fact that antihypertensive medication with β-blockers and calcium channel blockers [10,11], as well as ischemia [13], lead to adrenoceptor system hypersensitization, which may aggravate the myocardial malfunction owing to almost instant release of intrinsic myocardial noradrenaline [26,33], or by circulating adrenaline appearing some days after the occurrence of myocardial cell death [28].…”