Cardiovascular responses to microinjections of urocortin 3 into the nucleus tractus solitarius of the rat

Abstract

Nakamura T, Kawabe K, Sapru HN. Cardiovascular responses to microinjections of urocortin 3 into the nucleus tractus solitarius of the rat. Am J Physiol Heart Circ Physiol 296: H325-H332, 2009. First published December 5, 2008 doi:10.1152/ajpheart.01044.2008.-Urocortin 3 (Ucn3) is a new member of the corticotropin-releasing factor (CRF) peptide family and is considered to be a specific and endogenous ligand for CRF type 2 receptors (CRF2Rs). The presence of CRF 2 Rs has been reported in the nucleus tractus solitarius (NTS) of the rat. It was hypothesized that the activation of CRF 2Rs in the medial NTS (mNTS) may play a role in cardiovascular regulation. This hypothesis was tested in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (100 nl) of Ucn3 (0.03, 0.06, 0.12, and 0.25 mM) into the mNTS of anesthetized rats elicited decreases in mean arterial pressure (MAP: 5.0 Ϯ 1.0, 21.6 Ϯ 2.6, 20.0 Ϯ 2.8, and 12.7 Ϯ 3.4 mmHg, respectively) and heart rate (HR: 7.8 Ϯ 2.6, 46.2 Ϯ 9.3, 34.5 Ϯ 8.4, and 16.6 Ϯ 4.9 beats/min, respectively). Microinjections of artificial cerebrospinal fluid (100 nl) into the mNTS did not elicit cardiovascular responses. Maximum decreases in MAP and HR were elicited by 0.06 mM concentration of Ucn3. Cardiovascular responses to Ucn3 were similar in unanesthetized midcollicular decerebrate rats. A bilateral vagotomy completely abolished Ucn3-induced bradycardia. The decreases in MAP and HR elicited by Ucn3 (0.06 mM) were completely blocked by astressin (1 mM; nonselective CRFR antagonist) and K41498 (5 mM; selective CRF 2R antagonist). Microinjections of Ucn3 (0.06 mM) into the mNTS decreased the efferent greater splanchnic nerve activity. After the blockade of CRF2Rs in the mNTS, a Ucn3-induced decrease in the efferent sympathetic nerve discharge was abolished. These results indicate that Ucn3 microinjections into the mNTS exerted excitatory effects on the mNTS neurons via CRF2Rs, leading to depressor and bradycardic responses. blood pressure; corticotropin-releasing factor receptor antagonists; heart rate; sympathetic nerve activity; urocortin; nucleus tractus solitarius

The hypothalamic arcuate nucleus: a new site of cardiovascular action of angiotensin-(1–12) and angiotensin II

“…The procedures used in this study have been described in detail elsewhere (31,32). Briefly, rats were anesthetized with inhalation of isoflurane (2-3% in 100% O 2), one of the veins was cannulated, and urethane (1.2-1.4 g/kg) was injected intravenously in eight to nine aliquots at 2-min intervals.…”

“…Rectal temperature was maintained at 37.0 Ϯ 0.5°C. Blood pressure (BP) and HR were recorded by standard techniques (31,32).…”

“…Food and water were available to the animals ad libitum. Experiments were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and with the approval of the Institutional Animal Care and Use Committee of this university.The procedures used in this study have been described in detail elsewhere (31,32). Briefly, rats were anesthetized with inhalation of isoflurane (2-3% in 100% O 2), one of the veins was cannulated, and urethane (1.2-1.4 g/kg) was injected intravenously in eight to nine aliquots at 2-min intervals.…”

“…Rectal temperature was maintained at 37.0 Ϯ 0.5°C. Blood pressure (BP) and HR were recorded by standard techniques (31,32).Microinjections into the ARCN. Rats were placed in a prone position in a stereotaxic instrument with a bite bar 11 mm below the interaural line.…”

Muscimol microinjection into cerebellar fastigial nucleus exacerbates stress-induced gastric mucosal damage in rats

“…The discharge frequency of the GSN was measured as described [22] . It was recorded for 2 min by single barrel electrodes, wrapped with glass, before and after the microinjection of muscimol into the FN.…”