Tempol dose-dependently suppressed Ang II-induced phosphorylation of cardiovascular MAPKs and oxidative stress, but had no significant effect on the acute elevation of mean arterial blood pressure.
Does tempol treatment reduce cardiovascular MAPK activation and vasoconstriction induced by acute Ang II administration in conscious normotensive rats?
Acute administration of Ang II or phenylephrine increases oxidative stress leading to MAPK activation in cardiovascular tissues, but oxidative stress does not majorly contribute to the acute hypertensive response.
The relations among hypertensive response, oxidative stress, and mitogen-activated protein kinase (MAPK) in cardiovascular tissues have not been fully established. We investigated the involvement of reactive oxygen species on changes in the hemodynamics and cardiovascular MAPKs activities induced by acutely administered angiotensin II (Ang II) in conscious normotensive rats with or without treatment with a superoxide dismutase mimetic, 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol). Intravenous infusion of a pressor dose of Ang II rapidly increased mean arterial blood pressure (MBP) by 53+/-5 mm Hg. After a 30-minute treatment with Ang II, phosphorylated MAPKs (ERK1/2, JNK, p38) as well as thiobarbital reactive substances (T-BARS) were increased in the aorta and cardiac left ventricle. Tempol had no significant effect on the elevation of MBP elicited by Ang II; however, it dose-dependently suppressed the augmented phosphorylation of cardiovascular MAPKs and increased T-BARS levels in plasma and tissues induced by Ang II. An acutely administered pressor dose of phenylephrine, an alpha-adrenoceptor agonist, also showed tempol-sensitive cardiovascular MAPK activation and tempol-insensitive blood pressure elevation. These in vivo data indicate that acute administration of Ang II or phenylephrine provoked an increase in oxidative stress in the cardiovascular tissues leading to the activation of MAPKs, whether it was mediated by pressure overload or the direct action of these vasoconstrictors, and that oxidative stress might not have a major contribution to the acute hypertensive responses elicited by the vasoconstrictors.
Zhang et al. (Tue,) conducted a other in Normotensive rats. Tempol vs. Without tempol was evaluated on Changes in mean arterial blood pressure and cardiovascular MAPKs activities. Tempol dose-dependently suppressed Ang II-induced phosphorylation of cardiovascular MAPKs and oxidative stress, but had no significant effect on the acute elevation of mean arterial blood pressure.