Abstract

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.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.