Nitric oxide and central antihypertensive drugs - One more difference between catecholamines and imidazolines

NO is known to be involved in the peripheral and central regulation of the cardiovascular function. It plays a neuromodulatory role via a direct actio n on presynaptic nerve terminals, stimulating the release of gamma -aminobu tyric acid, glutamate, and norepinephrine. Our aim was to study the possibl e role of NO in the cardiovascular effects of the central antihypertensive drugs clonidine, rilmenidine, and alpha -methyl-norepinephrine (alpha -MNA) . Sites and mechanisms of the hypotensive action of these drugs were differ ent; clonidine and rilmenidine acted on imidazoline receptors in the nucleu s reticularis lateralis, whereas alpha -MNA acted upon alpha (2)-adrenocept ors in the nucleus tractus solitarius. The influence of N-G-nitro-L-arginin e, an NO synthase inhibitor, on the central hypotensive effects of these dr ugs was investigated in pentobarbital-anesthetized rabbits. The intracister nal (IC) administration of alpha -MNA (30 mug/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 <mu>g/kg IC) also induced hypotension (69+/-5 ve rsus 99+/-4 mm Hg) and bradycardia (266+/-7 versus 306+/-10 bpm) (P<0.05) ( n=5). In addition to clonidine, rilmenidine (1 <mu>g/kg IC) induced hypoten sion (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 <mu>g/kg I C) completely prevented the hypotensive effect of alpha -MNA but influenced the cardiovascular effects of neither clonidine nor rilmenidine. These res ults confirm that imidazoline drugs, such as clonidine, rilmenidine, and th e catecholamine alpha (2)-adrenoceptor agonist alpha -MNA, have distinct me chanisms of action.