Nitric Oxide and Central Antihypertensive Drugs

• DOI: 10.1161/01.hyp.37.2.246
• Publication Date: 2012-06-12T00:25:31Z
• Authors: Guata Yoro Sy; Véronique Bruban; Pascal Bousquet; Josiane Feldman
• Keywords: Male; Nordefrin; 0303 health sciences; Imidazoles; Blood Pressure; Nitric Oxide; Rilmenidine; Cardiovascular System; Nitroarginine; Clonidine; 3. Good health; 03 medical and health sciences; Catecholamines; Heart Rate; Animals; Rabbits; Hypotension; Oxazoles; Antihypertensive Agents

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 γ-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 α-methyl-norepinephrine (α-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 α-MNA acted upon α2-adrenoceptors in the nucleus tractus solitarius. The influence ofNG-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 α-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 withNG-nitro-l-arginine (900 μg/kg IC) completely prevented the hypotensive effect of α-MNA but influenced the cardiovascular effects of neither clonidine nor rilmenidine. These results confirm that imidazoline drugs, such as clonidine, rilmenidine, and the catecholamine α2-adrenoceptor agonist α-MNA, have distinct mechanisms of action.