Nitric oxide and superoxide anions in vascular reactivity of renovascular hypertensive rats.
The present study intends to define the role of the endothelium derived relaxing factor nitric-oxide (EDRF-NO) and the reactive oxygen intermediates in hypersensitivity to 5-hydroxytryptamine (5-HT) observed in abdominal aorta rings of two kidney-two clip hypertensive rats. Methylene Blue (which blocks production of cGMP by EDRF-NO) and Nw-nitro-L-arginine (which inhibits EDRF-NO synthesis), both shifted 5-HT dose-response curves to the left and completely abolished the differences in sensitivity to the agonist. The aortic perfusion with Krebs-Alcohol 20% (v/v) suppressed vascular relaxation to Ach (10(-5) M) and also abolished differences in sensitivity to 5-HT. These results suggest that a lower availability of EDRF-NO accounts for a higher 5-HT sensitivity in vessels of hypertensive rats. On the contrary, ridogrel (inhibitor of tromboxane-synthase and blocker of PGH2 and TxA2 receptors) did not suppress the hypersensitivity to 5-HT. In addition, since the superoxide anion (O2-) inactivates EDRF-NO, the effects of Superoxide dismutase (SOD) and Catalase (CAT) added in the bath were analyzed. Significant changes in sensitivity (P < 0.005) were found only for vessels of hypertensive rats (SOD depressing and CAT increasing sensitivity to 5-HT). Complementary, SOD activity was evaluated in the aorta homogenates and was found to be significantly lower in the hypertensive rats [(differences between hypertensive and sham rats, mU.mg wet weight tissue-1: 7 days after clipping, -183 +/- 67 (n = 11), P < 0.02; 21 days, -160 +/- 70 (n = 9), p < 0.05]. Results would indicate: 1. Lower EDRF-NO availability in vessels of the hypertensive animals which would account for higher sensitivity to 5-HT; 2. Such a lower EDRF-NO might depend, in part, upon its greater inactivation by O2- anions; 3. A greater presence of O2- anions in the vessels of hipertensive rats that might be favored by the lower SOD activity concentration in the vascular wall.
Vega
G W
GW
Departamento de Ciencias Fisiológicas, Facultad de Medicina, Universidad de Buenos Aires, Paraguay, Argentina.
Rosón
M I
MI
Bellver
A
A
Celentano
M M
MM
de la Riva
I J
IJ
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000503:physiopathology; D002374:Catalase / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D006978:Hypertension, Renovascular / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010421:Pentanoic Acids / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D010421:Pentanoic Acids; D011725:Pyridines; D013481:Superoxides; D009569:Nitric Oxide; D012701:Serotonin; D007650:Ketanserin; D002374:Catalase; D013482:Superoxide Dismutase; D013930:Thromboxane-A Synthase; D003042:Cocaine; C060219:ridogrel; D008751:Methylene Blue