Role of Calcitonin Gene-Related Peptide in Cooling-Induced Hemodynamic Perturbations in Rats: Investigation by Spectrum Analysis

Abstract

Calcitonin gene-related peptide (CGRP) and its receptors are widely distributed in the nervous and cardiovascular systems as a potent vasodilator; however, the underlying mechanisms of action of CGRP on cardiovascular regulation, such as cooling-elicited hemodynamic perturbation (CEHP), are still unclear. We used spectral and crossspectral analyses to explore such questions in this study. Conscious rats were pretreated with the CGRP antagonist CGRP_(8-37)-only, or following the removal of sympathetic influences using hexamethonium (HEX) or guanethidine (GUA) and then subjected the treated rats to a stressful cooling trial (CS). Cardiovascular indices were monitored via an implanted telemetric device throughout the experiment. The analyses included measurements of blood pressure (BP), heart rate (HR), cardiovascular variabilities (BPV, HRV), coherence linkage at very-low, low and high frequency regions (VLF: 0.02 to 0.2 Hz, LF: 0.2 to 0.6 Hz, and HF: 0.6 to 3.0 Hz), and dicrotic notch (Dn). Key findings of the hemodynamic indices and spectral changes in efferent sympathetic oscillations (LF) and myogenic oscillations (VLF) in comparison with the control vehicle were demonstrated: (I) under resting condition, CGRP_(8-37)- only increased the BP, HR and powers of VLF_(BPV), LF_(BPV). In contrast, the effects of CGRP_(8-37)-only were generally diminished or further reduced when the rats were pretreated with HEX or GUA. (II) Under CS condition, CGRP_(8-37)-only increased the HR but attenuated the power of LF_(BPV), converted the negative correlation (NC) into positive correlation (PC) for VLF_(HRV) with VLF_(BPV) (VLF pair) and LF_(HRV) with LF_(BPV) (LF pair). On the other hand, when pretreated with sympathetic removals, both HEX+CGRP_(8-37) and GUA+CGRP_(8-37) generally abolished the control coolinginduced pressor and tachycardia, attenuated or further reduced the effects of CGRP_(8-37)-only on VLF_(BPV), VLF_(HRV) and LF_(BPV). In addition, HEX+CGRP_(8-37) generally persisted the CGRP_(8-37)-only effect of PC for VLF and LF pairs, but GUA reversed the PC of VLF pair back to a NC tendency. Furthermore, cross-spectral analyses indicated that throughout the experiment, CGRP8-37-only enhanced the coherence linkage between BPV and HRV at the LF region but weakened that at the HF region. HEX+CGRP_(8-37) abolished the CGRP_(8-37)-only effect on the LF region but GUA+CGRP_(8-37) persisted the CGRP_(8-37)-only effects. Taken together, our results indicate that CGRP is dependent on the status of intrinsic sympathetic tonus to exert its function on cardiovascular regulation.