Endothelium-Derived Relaxing Factor-like Substance

We determined the effects of mono-L-arginine-containing compounds on pial arterioles of anesthetized piglets. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital microscopy. Diameter was determined during application of artificial cerebrospinal fluid containing no drugs and during application of 10-5 10-4, 10-3, and 10-2 M L-arginine (ARG), L-arginine ethyl ester (AEE), Na-benzoyl-Larginine (NBA), Nac.benzoyl-L-arginine ester ethyl (BAEE), and L-citrulline (CIT). Initial diameters were 100-200 ,um. All of these compounds dilated arterioles, but the threshold concentration needed to elicit dilation varied: 10M for NBA (n =5), 10-3 M for AEE (n =9) and BAEE (n=6), and 10-2 M for ARG (n-6) and CIT (n=4). Maximal responses were 15±8% for CIT, 17±4% for ARG, 19±8% for BAEE, 28±5% for NBA, and 27±6% for AEE. Indomethacin pretreatment (5 mg/kg i.v.) did not change arteriolar responses to AEE, NBA, and BAEE. However, coadministration of methylene blue (0.5x10-4 M or 0.5X10-3 M) abolished dilation to 10-3 M AEE or BAEE and attenuated dilation to 10'M NBA. In addition, coadministration of hemoglobin (0.4 x 10` M) abolished dilation to AEE, BAEE, or NBA. Last, intravenous (5 mg/kg) and coadministration (10-3 M) of NG-methyl-L-arginine blocked dilation to NBA or AEE. We conclude that mono-L-arginine-containing compounds produce pial arteriolar dilation in piglets, possibly involving an endothelium-derived relaxing factor. (Circulation Research 1990;67:1374-1380)