Potentiation of the hyporeactivity induced by in vivo endothelial injury in the rat carotid artery by chronic treatment with fish oil.
1. The present study investigates whether or not chronic feeding of rats with a diet enriched in fish oil affects the reactivity of balloon-injured carotid arteries. The left carotid arteries were injured in vivo by the repeated passage of a balloon catheter. Both the right (control artery) and the left carotid arteries were excised 24 h after the injury, and suspended in organ chambers for the measurement of changes in isometric tension in the presence of indomethacin. 2. Phenylephrine evoked similar concentration-contraction curves in the right (control) carotid arteries without endothelium from control and fish oil-fed rats. Balloon injury decreased the contractility of carotid arteries to phenylephrine in both types of rats and the pEC50 for phenylephrine was significantly decreased in balloon-injured arteries from control rats compared to those obtained in arteries from fish oil-fed rats (pEC50 7.59 +/- 0.1 and 7.28 +/- 0.06, respectively) while maximal contractions were similar (1.93 +/- 0.15 g and 1.79 +/- 0.12 g, respectively). 3. The treatment of control right carotid arteries without endothelium with either NG-nitro-L-arginine (an inhibitor of nitric oxide synthase) or superoxide dismutase (which protects nitric oxide from degradation) did not affect significantly the contractions to phenylephrine in either group. In these preparations, methylene blue (an inhibitor of soluble guanylate cyclase) decreased slightly but significantly maximal contractions to phenylephrine in both groups. The treatment of balloon-injured carotid arteries with NG-nitro-L-arginine or methylene blue partly restored contractions to phenylephrine in arteries from both types of rat. Superoxide dismutase further depressed the contractility to the alpha l-adrenoceptor agonist in balloon-injured arteries from control diet-fed rats but had no effect in balloon-injured preparations from fish oil-fed rats.4. 3-Morpholino-sydnonimine (SIN-1, a donor of nitric oxide) evoked similar concentration-dependent relaxations in control and balloon-injured carotid arteries from both types of rat.5. Balloon injury caused an increase in the tissue content of cyclic GMP in carotid arteries from control diet-fed rats. This production of cyclic GMP was abolished by N0-nitro-L-arginine. Superoxide dismutase potentiated significantly the production of cyclic GMP caused by balloon injury in control but not in fish oil-fed rats.6 These observations confirm that in vivo balloon injury causes the production of nitric oxide in the injured blood vessel wall. This production of nitric oxide from L-arginine accounts for the decreased contractility to phenylephrine and the accumulation of cyclic GMP in balloon-injured arteries. They further indicate that chronic feeding of rats with fish oil potentiates the L-arginine-nitric oxide pathway in the injured vessel leading to an enhanced hyporeactivity to phenylephrine.
Joly
G A
GA
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, TX 77030, USA.
Schini
V B
VB
Hughes
H
H
Vanhoutte
P M
PM
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects*; D020212:Carotid Artery Injuries; D002404:Catheterization / Q000009:adverse effects; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries; D005227:Fatty Acids / Q000097:blood; D005395:Fish Oils / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D019335:Nitroarginine; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D005227:Fatty Acids; D005395:Fish Oils; D014665:Vasodilator Agents; D010656:Phenylephrine; D019335:Nitroarginine; D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D013482:Superoxide Dismutase; D006152:Cyclic GMP; D008751:Methylene Blue; D007213:Indomethacin