CARDIOVASCULAR EFFECTS OF RILMENIDINE, A NEW α<sub>2</sub>‐ADRENOCEPTOR AGONIST, AND CLONIDINE IN CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS

Clinical and Experimental Pharmacology and Physiology - Tập 16 Số 11 - Trang 837-848 - 1989
Frederick Sannajust1, C. Julien1, Christian Barrès1, Catherine Cerutti1, E. Koenig‐Bérardd̊2, J Sassard1
1Department of Physiology and Clinical Pharmacology, Faculty of Pharmacy, Lyon, France
2Institut de Recherches Internationales Servier, Neuilly-sur-Seine, France

Tóm tắt

SUMMARY1. The acute and chronic effects of rilmenidine, a partial agonist of α1‐ and α2‐adrenoceptors with antihypertensive properties, were compared to those of clonidine on blood pressure (BP), heart rate (HR) and the urinary excretion of catecholamines, which was used as an index of sympathetic activity.2. As these drugs are known to interfere centrally and peripherally with the sympathetic nervous system, long‐term arterial blood pressure recordings in freely moving unstressed adult spontaneously hypertensive rats (SHR) were used.3. Acute i.v. administrations of rilmenidine (0.3 mg/kg at 1200 h, 1.2 mg/kg at 1700 and 2200 h) and clonidine (12 μg/kg at 1200 h, 50 μg/kg at 1700 and 2200 h) induced short‐lasting increases in BP associated with a decrease in HR, which were followed by prolonged, dose‐dependent decreases in BP without bradycardia. The pressor effect was less marked and the associated bradycardia was more marked in active SHR with physiologically high sympathetic activity than in resting SHR.4. A 12‐day oral treatment with rilmenidine (6.0 mg/kg daily) or clonidine (150 μg/kg daily) induced moderate decreases in BP without change in HR. Rilmenidine but not clonidine decreased normetanephrine (NMN) excretion in active but not in resting SHR.5. Finally, during the 24 h following the cessation of the treatments, BP returned to normal, without significantly exceeding that of untreated controls. However, upswings in BP or HR were observed, more markedly and frequently after clonidine than after rilmenidine.6. In conclusion the effects of α2‐adrenoceptor agonists appear to be influenced by the pre‐existing sympathetic tone. The general agreement between these data and those observed in patients demonstrates that the use of conscious unstressed animals is of value to determine the cardiovascular effects of drugs which act on the sympathetic nervous system.

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Clinical and Experimental Pharmacology and Physiology

Tập 16 Số 11

837-848

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