Permissive effect of nitric oxide in arachidonic acid induced dilation in isolated rat arterioles.
OBJECTIVE
Prostaglandins and nitric oxide play an important role in the regulation of arteriolar tone. L-Arginine analogues inhibit nitric oxide formation, but may also inhibit arachidonic-acid induced dilation. Nitric oxide was found to stimulate cyclooxygenase activity in cultured endothelial cells. Therefore, we hypothesized that the non-specific inhibition of prostaglandin-related dilation by L-arginine analogues is a consequence of the absence of nitric oxide.


METHODS
To test this hypothesis, arteriolar segments from rat cremaster muscle were studied in a pressure myograph at 75 mmHg. Segments developed spontaneous tone, the diameter reduced from 179 +/- 3 to 98 +/- 3 microns (n = 41). In this condition, responses to exogenous arachidonic acid (1 microM) were recorded and compared with responses after addition of L-NNA, and addition of either SNAP, nitroprusside or 8-Br-cGMP in the presence of L-NNA.


RESULTS
Inhibition of basal nitric oxide production with L-NNA (0.1 mM) reduced arachidonic acid-induced dilation (from 52 +/- 9 to 31 +/- 6 microns). In the presence of L-NNA, responses to arachidonic acid were augmented when exogenous nitric oxide was also present (SNAP, 31 +/- 6 microns vs. 75 +/- 5 microns; nitroprusside, 31 +/- 8 microns vs. 42 +/- 7 microns). Responses were not augmented with the second messenger of nitric oxide-mediated dilation 8-Br-cGMP (37 +/- 9 microns vs. 32 +/- 9 microns).


CONCLUSIONS
These results indicate that nitric oxide directly increases arachidonic acid-induced dilation. Thus, the non-specific effect of L-arginine analogues can be explained by a permissive effect of nitric oxide on endothelial arachidonic acid metabolism.
Bakker
E N
EN
Laboratory for Physiology, Institute for Cardiovascular Research (ICaR-VU), Vrije Universiteit, Amsterdam, Netherlands.
Sipkema
P
P
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D001160:Arterioles; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009213:Myography; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D016718:Arachidonic Acid; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D006152:Cyclic GMP