Pcroxynilrite is formed cndogenously hy the near diffusion-limited reaction of nitric oxide with superoxide anion. Peroxynitrite nitrates free and protein-associated ivrosine residues to specifically form 3-nilro-L-tyrosine (NT). The similarity in chemical structure of NT to the endogenous catecholamines prompted investigation of: (i) the effects of administration of NT (2.5 (imol/kg, i.v.) on baseline mean arterial pressure (MAP) and hmdquarter (HQR). renal (RR), and mesenteric (MR) vascular resistances; (ii) the effects of administration of NT (2.5 u,mol/kg. i.v.) on the subsequent changes in MAP, HQR, RR. and MR induced hy the i. v. administration of the endogenous catecholamines norepmephrine (NE) and epinephrine (EPI), the specific a-adrenoceptor agonist phenylephrine (PE). and the specific β- adrenoceptor agonist isoprolcrenol (ISO); and dii) (he effects of administration of NT (2.5 fimol/kg, i.v.) on the subsequent changes m MAP. HQR, RR. and MR induced by the i. v. administration of the non-catecholanune vasoconstrictors angiotensin II (All) and argimne vasoprcssin (AVP); in penlobarbitalanesthetized rats. NT caused no immediate changes in MAP, HQR. RR, or MR, however, a progressive increase in MAP was noted to occur over time. NE and PE caused increases in MAP, RR, MR, and HQR, while EPI caused increases in MAP, RR, and MR and a decrease in HQR. ISO caused decreases in MAP, RR, MR. and HQR. These hemodynamic responses were all significantly attenuated following the administration of NT. Furthermore, the hemodynamic responses became further attenuated over time. AH and AVP induce increases in MAP, RR, MR, and HQR. The hemodynamic changes induced by AVP remain unchanged following the administration of NT, hut the responses to All were partially diminished. However, All hemodynamic responses are also partially attenuated by prazosin, a specific a ]-adrenoceptor antagonist. These studies demonstrate that (i) NT is a potent inhibitor of a- and β-adrenoceoptor-mediaied hemodynamic responses in vivo.
|Original language||English (US)|
|State||Published - Dec 1 1996|