Induction of bradycardia in trout by centrally administered corticotropin-releasing-hormone (CRH)

The cardiovascular effects of centrally and peripherally administered synthetic salmon corticotropin-releasing-hormone (CRH), a member of a family of stress-related neuropeptides, were investigated in the unanesthetized trout, Oncorhynchus mykiss. In group 1, trout bearing a cannula in the dorsal aorta, neither intracerebroventricular (i.c.v.) nor intra-arterial (i.a.) injections of CRH produced any significant change in mean heart rate (HR) and mean dorsal aortic blood pressure. These results stand in contrast to the previously reported hypertensive effects of i.a. and i.c.v. injections of trout urotensin-I. In group 2, non-cannulated trout bearing two subcutaneous electrocardiographic electrodes, conditions that are considered to be less stressful to the animals, the baseline level of HR was significantly reduced compared to the corresponding value for cannulated trout. In these trout, no significant change occurred in the HR after i.c.v. administration of 1 pmol of CRH. However, i.c.v. injection of 5 pmol of CRH caused a 12% (P<0.01) decrease in HR during the 20-25 min post-injection period. In addition, the heart rate variability (HRV), a marker of vagal input to the heart, was increased by 120%. The CRH antagonist, CRH-(9-41)-peptide alone had no effect on HR or HRV but blocked CRH-induced bradycardia. In the non-cannulated trout, i.c.v. injection of trout urotensin-I (5 pmol) produced no significant change in HR and HRV. In contrast, i.c.v. administration of angiotensin II (5 pmol) elicited a highly significant 33% (P<0.001) increase in the mean HR as well as inducing a marked (64%) reduction in HRV. Our results suggest that picomolar doses of CRH act centrally to evoke a bradycardia by a probable mechanism that involves enhancement of the parasympathetic drive to the heart.