Cardiovascular actions of adrenocorticotropin microinjections into the nucleus tractus solitarius of the rat.

The presence of adrenocorticotropin (ACTH) containing cells and melanocortin (MC) receptors has been reported in the nucleus tractus solitarius (NTS) of the rat. The importance of the NTS in the regulation of cardiovascular function is also well established. Based on these reports, it was hypothesized that ACTH acting within the NTS may modulate the central regulation of cardiovascular function. To test this hypothesis, cardiovascular effects of ACTH in the NTS were investigated in intact urethane-anesthetized and unanesthetized decerebrate, artificially ventilated, adult male Wistar rats. Microinjections of ACTH (0, 0.5, 1, 2, and 4 mM) into the medial subnucleus of NTS (mNTS) elicited decreases in mean arterial pressure (MAP; 0+/-0, 24.4+/-3.5, 35.7+/-4.3, 44.5+/-5.8 and 53.7+/-5.6 mm Hg, respectively) and heart rate (HR; 0+/-0, 25.7+/-5.3, 35.5+/-6.4, 47.5+/-12.1 and 55.0+/-5.6 beats/min, respectively). The onset and duration of the responses to microinjections of ACTH (0.5-4 mM) were 5-10 s and 45-120 s, respectively. Control microinjections of artificial cerebrospinal fluid (aCSF) did not elicit any response. The volume of all microinjections was 100 nl. The concentrations of ACTH that elicited depressor and bradycardic responses when microinjected into the mNTS (e.g. 1 or 2 mM, 100 nl), did not elicit a response when injected i.v. (n=5) or i.c.v. (n=2) indicating that there was no leakage of the drug from the injection site in the mNTS. Microinjections of MC3/4 receptor antagonists (acetyl-[Nle(4), Asp(5), d-2-Nal(7), Lys(10)]-cyclo-alpha-MSH amide, fragments 4-10 (SHU9119) and agouti-related protein (83-132) amide) into the mNTS blocked the responses to ACTH. Microinjections of ACTH (2 mM) into the mNTS decreased efferent greater splanchnic nerve activity. Bilateral vagotomy significantly attenuated ACTH-induced bradycardia. These results indicated that: 1) microinjections of ACTH into the mNTS elicited depressor and bradycardic responses, 2) these responses were mediated via MC3/4 receptors, 3) the depressor effects were mediated via a decrease in the activity of the sympathetic nervous system, and 4) the bradycardic responses were vagally mediated.