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

Abstract

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 CRF2Rs 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 +/- 1.0, 21.6 +/- 2.6, 20.0 +/- 2.8, and 12.7 +/- 3.4 mmHg, respectively) and heart rate (HR: 7.8 +/- 2.6, 46.2 +/- 9.3, 34.5 +/- 8.4, and 16.6 +/- 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 CRF2R 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.

• Authors: Takeshi Nakamura, Kazumi Kawabe, Hreday N Sapru
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 296 Issue 2 Pg. H325-32 (Feb 2009) ISSN: 0363-6135 [Print] United States
• PMID: 19060121 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Amphibian Proteins
• CRF receptor type 2
• Peptide Fragments
• Peptide Hormones
• Receptors, Corticotropin-Releasing Hormone
• Urocortins
• astressin
• sauvagine
• Corticotropin-Releasing Hormone

Topics

• Amphibian Proteins (pharmacology)
• Anesthesia, General
• Animals
• Blood Pressure (drug effects)
• Bradycardia (chemically induced, physiopathology)
• Corticotropin-Releasing Hormone (pharmacology)
• Decerebrate State
• Dose-Response Relationship, Drug
• Heart (innervation)
• Heart Rate (drug effects)
• Hypotension (chemically induced, physiopathology)
• Male
• Microinjections
• Peptide Fragments (pharmacology)
• Peptide Hormones (pharmacology)
• Rats
• Rats, Wistar
• Receptors, Corticotropin-Releasing Hormone (antagonists & inhibitors, metabolism)
• Respiration, Artificial
• Solitary Nucleus (drug effects, metabolism)
• Splanchnic Nerves (drug effects)
• Urocortins (administration & dosage, metabolism)
• Vagotomy