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(Hypertension. 2001;37:246.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Nitric Oxide and Central Antihypertensive Drugs

One More Difference Between Catecholamines and Imidazolines

Guata Yoro Sy; Véronique Bruban; Pascal Bousquet; Josiane Feldman

From the Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.

Correspondence to Dr P. Bousquet, Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Faculté de Médecine, Université Louis Pasteur, 11 rue Humann, 67000 Strasbourg, France. E-mail Pascal.Bousquet{at}medecine.u-strasbg.fr

NO is known to be involved in the peripheral and central regulation of the cardiovascular function. It plays a neuromodulatory role via a direct action on presynaptic nerve terminals, stimulating the release of -aminobutyric acid, glutamate, and norepinephrine. Our aim was to study the possible role of NO in the cardiovascular effects of the central antihypertensive drugs clonidine, rilmenidine, and -methyl-norepinephrine (-MNA). Sites and mechanisms of the hypotensive action of these drugs were different; clonidine and rilmenidine acted on imidazoline receptors in the nucleus reticularis lateralis, whereas -MNA acted upon ₂-adrenoceptors in the nucleus tractus solitarius. The influence of N^G-nitro-L-arginine, an NO synthase inhibitor, on the central hypotensive effects of these drugs was investigated in pentobarbital-anesthetized rabbits. The intracisternal (IC) administration of -MNA (30 µg/kg) induced hypotension (79±2 versus 103±4 mm Hg) and bradycardia (222±8 versus 278±4 bpm) (P<0.05) (n=5). Clonidine (0.07 µg/kg IC) also induced hypotension (69±5 versus 99±4 mm Hg) and bradycardia (266±7 versus 306±10 bpm) (P<0.05) (n=5). In addition to clonidine, rilmenidine (1 µg/kg IC) induced hypotension (64±4 versus 97±4 mm Hg) and bradycardia (264±11 versus 310±4 bpm) (P<0.05) (n=5). Pretreatment with N^G-nitro-L-arginine (900 µg/kg IC) completely prevented the hypotensive effect of -MNA but influenced the cardiovascular effects of neither clonidine nor rilmenidine. These results confirm that imidazoline drugs, such as clonidine, rilmenidine, and the catecholamine ₂-adrenoceptor agonist -MNA, have distinct mechanisms of action.

Key Words: nitric oxide • blood pressure • clonidine • norepinephrine • central nervous system