Melanocortin‐4 receptors in the PVN and RVLM are important in mediating cardiovascular responses to acute stress (686.7)

Abstract

Our previous studies demonstrate an important role for the brain melanocortin system in regulating sympathetic nervous system activity and blood pressure (BP) as well as in modulating BP responses to stress. However, the brain regions involved in melanocortin‐4 receptors (MC4R)‐mediated modulation of cardiovascular responses to acute stress are unknown. In this study, we examined whether rescue of MC4R specifically in the paraventricular nucleus of the hypothalamus (PVN) or in the rostral ventrolateral medulla (RVLM) of whole‐body MC4R deficient mice (LoxTB‐MC4R mice) restores BP response to acute air‐jet stress. Using Cre‐loxP technology we selectively rescued MC4R in the PVN (LoxTB‐MC4R/Sim1, n=5) or RVLM (Cre‐RVLM/LoxTB‐MC4R mice, n=5). Mice were implanted with telemetry probes for measurement of mean arterial pressure (MAP). After a 10‐day recovery period, baseline MAP was measured for 3 consecutive days and during an acute air‐jet stress test. MAP was continuously measured for 30 minutes before, during and 30 minutes after the stress test. LoxTB‐MC4R mice were slightly heavier (53±2 vs 43±1 and 48±3 g), but had similar baseline MAP (109±1 vs 110±1 and 113±2 mmHg) compared to LoxTB‐MC4R/Sim1 and Cre‐RVLM/LoxTB‐MC4R mice. Acute air‐jet stress significantly increased MAP by 28±2 and 33±2 mmHg in loxTB‐MC4R/Sim1 and Cre‐RVLM/LoxTB‐MC4R compared to only 22±2 mmHg in loxTB‐MC4R mice. These results indicate that MC4Rs in PVN and RVLM neurons participate in the modulation of BP response to acute stress. (NHLBI‐PO1HL51971, NIGMS P20GM104357 and AHA SDG5680016)Grant Funding Source: AHA and NIH