Riedel M W, Anneser F, Haberl R L
Ludwig-Maximilians-Universität München, Klinikum Grosshadern, Germany.
Brain Res. 1995 Feb 6;671(1):21-6. doi: 10.1016/0006-8993(94)01292-p.
We evaluated the response of pial arterioles to L-arginine in anesthetized normotensive rats and spontaneously hypertensive rats equipped with a closed cranial window. Topical application of 10(-6)-10(-4) mol/l L-arginine, which is known to be the endogenous substrate for the synthesis of nitric oxide, induced dose-dependent arteriolar vasodilation. The response was more pronounced in hypertensive than in normotensive rats (at the concentration of 10(-4) mol/l L-arginine: 18.3 +/- 3.3% vs. 6.7 +/- 1.7%, respectively, means +/- S.E.). The stereoisomer D-arginine had no effect in hypertensive rats. Topical application of the nitric oxide synthase inhibitor N-nitro-L-arginine converted L-arginine-induced dilation to constriction in normotensive and hypertensive rats. The cyclooxygenase inhibitor indomethacin (5 micrograms/ml cerebrospinal fluid) also blocked the dilation in both strains. Photochemical endothelial injury blocked L-arginine-induced dilation in normotensive rats, but only partly antagonized the response in hypertensive animals. Intravenous or topical pretreatment with the free radical scavenger superoxide dismutase significantly reduced the dilating response to 10(-4) mol/l L-arginine in hypertensive rats. Superoxide dismutase did not significantly change the response to L-arginine in normotensive animals. It is concluded that nitric oxid formation in the endothelium and liberation of cyclooxygenase products cause L-arginine-induced dilation in normotensive rats. While nitric oxide and cyclooxygenase products are also involved in L-arginine-induced dilation in spontaneously hypertensive rats, superoxide radicals contribute to the enhanced response in this strain. This mechanism appears to be specific for the hypertensive animals and is only partly dependent on an intact endothelium.
