L-arginine analogues blunt prostaglandin-related dilation of arterioles
Koller, A.; Sun, D.; Messina, E.J.; Kaley, G.
American Journal of Physiology 264(4 Pt 2): H1194-H1199
1993
ISSN/ISBN: 0002-9513 PMID: 8476097 Document Number: 421543
The effects of arginine analogues, inhibitors of endothelium-derived nitric oxide synthesis, on dilation of arterioles in response to various vasoactive substances were studied. At 65 mmHg intravascular pressure, isolated arterioles of rat cremaster muscle developed tone spontaneously and achieved control diameters similar to those observed in vivo (84.1 +- 2.0 mu-m vs. passive diameter: 161.3 +- 3.4 mu-m). Acetylcholine (ACh, 5 times 10-8 M), sodium nitroprusside (SNP, 5 times 10-8 M), arachidonic acid (AA, 10-7 M), prostaglandin E-2 (PGE-2, 10-9 M), and adenosine (ADO, 10-6 M) were added to the Krebs bicarbonate buffer solution, suffusing the vessels. The peak vasodilator effects of all agents were studied before and after the administration of various doses of N-omega-nitro-L-arginine (L-NNA; 10-5, 10-4, and 10-3 M), which significantly reduced, in a dose-dependent manner, the basal diameter of arterioles by 3.6, 15.2, and 18.9%, respectively. The lowest concentration of L-NNA significantly inhibited arteriolar dilations to ACh by apprx 26%. Higher concentrations of L-NNA and N-omega-monomethyl-L-arginine (L-NMMA; 10-4 M) caused a further significant reduction in the dilation to ACh (to apprx 47%) and also significantly reduced dilator responses to AA and PGE-2. In the presence of the highest concentration of L-NNA (10-3 M), dilation to SNP and ADO were also significantly reduced. Removal of endothelium abolished dilation to ACh and AA but did not alter that to SNP, PGE-2, or ADO. In the absence of endothelium, L-NNA did not significantly affect basal arteriolar diameter, but at the highest concentration utilized (10-3 M), caused a reduction in the dilation to the agents studied. These findings suggest that in isolated skeletal muscle arterioles dilation to ACh is mediated entirely by endothelial factors, most prominently by nitric oxide (or a related compound). Higher doses Of L-arginine analogues, however, blunt the effects of dilator agents that are known not to be mediated by endothelium-derived relaxing factor. Thus the use of arginine analogues requires caution, appropriate controls, and careful interpretation of results.