N-Acetylcysteine Antagonizes the Development But Does Not Reverse ACTH-Induced Hypertension in the Rat

Abstract

We investigated the effect of antioxidant N-acetylcysteine (NAC) on adrenocorticotropic hormone (ACTH)-hypertension. Male Sprague-Dawley rats received NAC (10 mg/L) or water 4 days before ACTH/saline treatment for 13 days (prevention study). In a reversal study, NAC commenced on day 8 of ACTH/saline treatment and continued for 5 days. ACTH increased systolic blood pressure (SBP) in water drinking rats (111 +/- 1 to 131 +/- 3 mmHg, p < 0.001). In the prevention study, NAC + ACTH increased SBP (108 +/- 2 to 120 +/- 2 mmHg, p < 0.001) but less than ACTH alone (p' < 0.05). In the reversal study, NAC had no significant effect (132 +/- 4 to 124 +/- 3 mmHg, ns). Thus, NAC partially prevented but did not reverse ACTH-induced hypertension.

N-acetylcysteine-induced vasodilation involves voltage-gated potassium channels in rat aorta

“…strategies for treatment of cardiovascular diseases, especially hypertension-related diseases (Kaczorowski and Garcia 1999; Li et al 2005). In retrospect, the observation that Kv channels were involved in NAC-induced vasodilation may be responsible for the depressor effect of NAC in animal and human study, which was previously ascribed to its ROS scavenging properties (Girouard et al 2003;Lachmanova et al 2005;Rauchova et al 2005;Mondo et al 2006;Pechanova et al 2006;Zicha et al 2006;Krug et al 2008). Therefore, the use of NAC as a ROS scavenger potentially leads to an overestimation of the role of ROS in vasculture, especially in the study of hypertension-related diseases.…”

“…Due to its potent ROS scavenging capacities, NAC has largely been used in the study of various cardiovascular diseases, and proved to be effective as expected according to theory. For instance, it was demonstrated that NAC decreased blood pressure (BP) in various hypertensive animal models induced by N ω -Nitro-L-arginine methyl ester (L-NAME), adrenocorticotropic hormone (ACTH) or dexamethasone, as well as in spontaneous hypertensive rats (Rauchova et al 2005;Mondo et al 2006;Pechanova et al 2006;Krug et al 2008). There are also clinical studies demonstrating that NAC decreased systolic blood pressure (SBP) in hypertensive patients (Barrios et al 2002;Martina et al 2008).…”

Lipid Peroxidation and Antioxidants in Arterial Hypertension

“…Attenuated hypertension in young SHR [265] Prevented the development of glucocorticoidinduced hypertension [202] Prevented the development of adrenocorticotropic hormone-induced hypertension [266] Markedly reduced salt-sensitive hypertension [267] Prevented/ attenuated hypertension induced by nitric oxide synthesis inhibition [268] Failed to reduce blood pressure in adult SHR [265] Failed to attenuate glucorticoidinduced hypertension [202] Failed to reverse adrenocorticotropicinduced hypertension [266] Failed to prevent the development of hypertension induced by the blockade of nitric oxide synthesis [256] …”

Hypertension and other morbidities with Cushing&rsquo;s syndrome associated with corticosteroids: a review

“…Increased oxidative stress, reflected in increased superoxide production and elevated levels of plasma F2-isoprostanes, constitutes a common underlying disorder in both forms of CS and is prevented and reversed by antioxidants (folic acid, N -acetylcysteine, tempol, and apocynin) but not with BH4 or allopurinol 121–123. In both conditions, HT has been associated with decreased NO bioavailability, reflected in decreased plasma reactive nitrogen intermediates (nitrate/nitrite) 122,123…”