Aminoethylisothiourea (AET) is a potent inhibitor of inducible nitric oxide synthase (NOS). The present study was performed to investigate whether AET and its rearrangement products might modulate vascular contraction independently of its effects as a NOS inhibitor in rat small femoral arteries. AET caused an endothelium-independent increase in contraction induced by norepinephrine (NE). This effect was not affected by either N(omega)-nitro-L-arginine methyl ester, nitro-L-arginine, indomethacin or propanolol, but it was suppressed in Ca(2+)-free medium. AET enhanced extracellular Ca(2+) component of NE-induced contraction, and this effect was prevented by the receptor-mediated Ca(2+) entry blocker, 1-{beta-[3-(p-methoxyphenyl)-propyloxyl]-p-methoxyphenetyl}- 1H-imidaz ole hydrochloride (SK&F 96365), but not by the voltage-dependent Ca(2+) channel blocker, nitrendipine. AET did not alter the response to CaCl(2) in vessels exposed to KCl depolarization. The protein kinase C (PKC) inhibitor, 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) (GF 109203X), prevented the potentiating effect of AET on the NE response. AET failed to produce an increase in tone in the presence of NE and GTP in permeabilized arteries. Among the AET rearrangement products, mercaptoethylguanidine produced an endothelium-independent increase in the NE response. 2-aminothiazoline had no effect, and guanidinoethyldisulphide produced relaxation. The effect of mercaptoethylguanidine was dependent on extracellular Ca(+) and was prevented by GF 109203X. These results indicate that AET is able to potentiate the contraction to NE in rat femoral resistance arteries independently of its inhibitory effect on either NOS or cyclo-oxygenase. Its effect occurs via an enhancement of SK&F 96365-sensitive Ca(2+) entry. A PKC inhibitor-sensitive mechanism also appears to be involved in the AET effect. Mercaptoethylguanidine potentiates NE response through a mechanism similar to AET.