Nitric Oxide and Central Antihypertensive Drugs

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Abstract
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 α 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 α-MNA (30 μg/kg) induced hypotension (79±2 versus 103±4 mm Hg) and bradycardia (222±8 versus 278±4 bpm) ( P P P N G -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 α 2 -adrenoceptor agonist α-MNA, have distinct mechanisms of action.