Stress-mediated heart rate dynamics after deletion of the gene encoding corticotropin-releasing factor receptor 2.

Abstract

The objective of the present study was to investigate the potential role of corticotropin-releasing factor receptor subtype 2 (CRFR2) in autonomic regulation of heart rate and heart rate variability under physiological conditions in conscious mice. Heart rate dynamics during novelty exposure and auditory fear conditioning were assessed by radiotelemetry. Heart rate responses and heart rate variability values were not different in CRFR2+/+ and CRFR2-/- mice during novelty exposure, which was associated with similar locomotor activity exhibited by both genotypes. The heart rate responses during retention of conditioned auditory fear were similar and the exponential relationship between heart rate and heart rate variability was independent of genotype. Pharmacological stimulation of the peripheral CRFR2beta by intraperitoneal injection of 200 ng human/rat corticotropin-releasing factor yielded a sustained tachycardia in wildtype control (CRFR2+/+) mice which was absent in CRFR2-deficient (CRFR2-/-) mice. Similarly, the tachycardia was effectively blocked by preinjection of the CRFR2 antagonist antisauvagine-30. In conclusion, the results indicate the involvement of CRFR2 in heart rate dynamics upon pharmacological stimulation but demonstrate that CRFR2 is not involved in baseline heart rate regulation and stress-mediated modulation of heart rate responses.