Central ventilatory and cardiovascular actions of calcitonin gene-related peptide in unanesthetized trout

Abstract

SUMMARYCalcitonin gene-related peptide (CGRP) and its receptors are widely distributed in the tissues of teleost fish, including the brain, but little is known about the ventilatory and cardiovascular effects of the peptide in these vertebrates. The present study was undertaken to compare the central and peripheral actions of graded doses (5-50pmol) of trout CGRP on ventilatory and cardiovascular variables in unanesthetized rainbow trout. Compared with vehicle, intracerebroventricular injection of CGRP significantly elevated the ventilation frequency (f V ) and the ventilation amplitude (V AMP ) and, consequently, the total ventilation (V TOT ). The maximum hyperventilatory effect of CGRP (V TOT : +300%), observed at a dose of 50pmol, was mostly due to its stimulatory action on V AMP (+200%) rather than f V (+30%). In addition, CGRP produced a significant and dose-dependent increase in mean dorsal aortic blood pressure (P DA ) (50pmol: +40%) but the increase in heart rate (f H ) was not significant. Intra-arterial injections of CGRP were without effect on the ventilatory variables but significantly and dose-dependently elevated P DA (50pmol: +36%) without changing f H . At the highest dose tested, this hypertensive phase was preceded by a rapid and transient hypotensive response. In conclusion, our study suggests that endogenous CGRP within the brain of the trout may act as a potent neurotransmitter and/or neuromodulator in the regulation of cardio-ventilatory functions. In the periphery, endogenous CGRP may act as a local and/or circulating hormone preferentially involved in vasoregulatory mechanisms.

Evaluation of cardiovascular parameters in cynomolgus monkeys following IV administration of LBR-101, a monoclonal antibody against calcitonin gene-related peptide

“…Similar dual effects may also help to explain the paradoxical minor effect observed on the blood pressure (minor reduction vs. increase) and heart rate (decrease), since there seem to exist differences, in terms of vasodilation, between inhibiting CGRP only at the nerve endings or throughout the entire central and peripheral nervous systems. It has been suggested that CGRP in the central nervous system is associated with regulation of various hemodynamic parameters, 32 , 33 while peripheral inhibition of CGRP does not induce any hemodynamic changes, likely due to the number of overlapping compensatory mechanisms that are involved in the modulation of blood pressure 34 . In other words, CGRP can interfere with the control of blood pressure via modulating central synapses but, at the peripheral level, its inhibition would be counterbalanced by other hemodynamically active substances (nitric oxide, brain natriuretic peptide and catecholamines).…”

Brain neuropeptides in central ventilatory and cardiovascular regulation in trout

“…The anorexigenic action of centrally administered CGRP in the goldfish Carassius auratus has been previously described (Martinez-Alvarez et al, 2009). The cardio-ventilatory actions of centrally administered trout CGRP in trout has been recently described (Le Mével et al, 2012). …”