EFFECT OF NG-MONOMETHYL-L-ARGININE ON ARCADE ARTERIOLES OF RAT SPINOTRAPEZIUS MUSCLES

The effect of the specific inhibitor of nitric oxide (NO) formation N(G)-monomethyl-L-arginine (L-NMMA) on resting arteriolar diameter and on actions of both endothelium-dependent and -independent vasoactive substances was investigated using intravital microscopy in rats. The spinotrapezius muscle of anesthetized normotensive rats was suspended in a Krebs-Henseleit bath containing tetrodotoxin (3 x 10(-7) M), indomethacin (2.8 x 10(-5) M), and propranolol (10(-6) M) to block sympathetic nerve conduction, prostacyclin formation, and beta-adrenergic receptors, respectively. Acetylcholine (ACh), nitroprusside (NP), norepinephrine (NE), phenylephrine (PE), and guanabenz (GB) were topically applied before and after superfusion of L-NMMA (10(-5) to 10(-4) M). Superfusion of L-NMMA reduced arteriolar diameter and caused dose-dependent increases in arteriolar tone. The onset of action of L-NMMA was nearly immediate. L-NMMA inhibited vasodilator responses to the endothelium-dependent vasodilator ACh but not to the endothelium-independent NP. NE induced dose-related vasoconstriction that was significantly potentiated by L-NMMA. These effects were partially reversed by addition of L-arginine (10(-3) M). Potentiation of vasoconstriction elicited by NE was still observed after inhibition of alpha-1-adrenoceptors with prazosin, but potentiation was abolished by the alpha-2-adrenoceptor antagonist yohimbine. L-NMMA potentiated arteriolar vasoconstriction elicited by the alpha-2-adrenergic receptor agonist GB but not by the alpha-1-adrenoceptor agonist PE. These findings with L-NMMA suggest that resting diameter of arterioles is modulated by endogenous NO biosynthesis and that endothelium-dependent vasodilators act through the formation of endogenous NO to exert their action in vivo. NE induces NO formation, most likely through activation of alpha-2-adrenoceptors on endothelial cells, attenuating the direct activation of vascular smooth muscle cells to constrict.