Abstract 605: Calcitonin Gene Related Peptide (cgrp) And Its Role In Cardiovascular And Autonomic Regulation
Calcitonin gene related peptide (CGRP) is the most potent microvascular vasodilator known. It exerts effects centrally as well as in the gastrointestinal, respiratory and endocrine system. However, its role in cardiovascular regulation remains controversial. We studied the hemodynamic and autonomic function in CGRP knockout (KO) mice. Blood pressure (BP), heart rate (HR) and activity level were assessed at least one week after mice were implanted with telemeters. Ten CGRP KO and ten wild type (WT) mice (3-4month old) were used in this study. After the recording period, 24-hr urine and blood were collected for assessment of catecholamine and their metabolites. To study the baroreflex sensitivity, phenylephrine and sodium nitroprusside were administered in an acute study with seven mice from each group. We found higher blood pressure at rest during daytime in the CGRP KO mice (102.4 ± 1.652mmHg, vs. 110.5 ± 3.242mmKg, p = 0.039), though not in 24-hr mean arterial pressure (MAP) (105.0 ± 1.789mmHg, vs. 112.1 ± 3.123mmHg, p = 0.05). There was no difference in HR in the two groups (KO: 566.4 ± 12.09; WT: 581.9 ± 8.544, p = 0.31). Norepinephrine was greatly elevated in both plasma and 24-hr urine in KO mice (in urine: KO: 956.7 ± 90.65 pg/ml, WT: 618.1 ± 46.15pg/ml, p = 0.004; in plasma: KO: 2505 ± 596.3pg/ml, n=6, WT: 1168 ± 98.05 pg/ml, p = 0.04). Baroreflex sensitivity was higher in the KO mice (KO: 3.217 ± 0.6852 ms/mmHg, n=7, WT: 1.398 ± 0.2583 ms/mmHg, n=7, p=0.03). The activities level was slightly lower in the KO mice (KO: 6.717 ± 1.059 counts/min, WT: 10.59 ± 1.787 counts/min p = 0.08). However, KO mice that were 6-8 month old were heavier compared to WT mice of the same age (KO: 30.65 ± 0.6009 g, n=17, WT: 27.89 ± 0.6345 g, n=17, p = 0.004). While CGRP might seem to contribute less to the physiological regulation of blood pressure in young adult mice due to their better baroreflex function, it likely contributes to blood pressure and sympathetic activation in older mice. Therefore, further study in BP, HR and metabolic syndromes in old CGRP KO mice is required.
- © 2012 by American Heart Association, Inc.