Chronic central ghrelin infusion reduces blood pressure and heart rate despite increasing appetite and promoting weight gain in normotensive and hypertensive rats

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2013-04, Vol.42, p.35-42
• Main Authors: Freeman, John N., Carmo, Jussara M. do, Adi, Ahmad H., da Silva, Alexandre A.
• Format: Article
• Language: English
• Subjects: animal disease models; Animals; appetite; Baroreceptor function; Blood pressure; Blood Pressure - drug effects; body weight changes; Bradycardia - chemically induced; Bradycardia - physiopathology; central nervous system; Eating - drug effects; Food intake; Ghrelin; Ghrelin - administration & dosage; Ghrelin - pharmacology; heart; Heart rate; Heart Rate - drug effects; hypertension; Infusions, Intraventricular; Leptin; Male; males; Pressoreceptors - metabolism; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; telemetry; weight gain; Weight Gain - drug effects
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2013.02.003

► Chronic CNS ghrelin infusion increases appetite and promote weight gain. ► Chronic CNS ghrelin infusion reduces BP and HR despite weight gain and hyperphagia. ► Ghrelin's effect on BP and HR is associated with reduced cardiac sympathetic tone. Acute studies showed that ghrelin acts on the central nervous system (CNS) to reduce blood pressure (BP), heart rate (HR) and sympathetic activity. However, the long-term CNS cardiovascular actions of ghrelin are still unclear. We tested whether chronic intracerebroventricular (ICV) infusion of ghrelin causes sustained reductions in BP, HR and whether it alters baroreceptor sensitivity (BRS) and autonomic input to the heart. A cannula was placed in the lateral ventricle of male Sprague–Dawley (SD) rats for ICV infusions via osmotic minipump (0.5μl/h). BP and HR were measured 24-h/day by telemetry. After 5 days of control measurements, ghrelin (0.21nmol/h) or saline vehicle were infused ICV for 10 days followed by a 5-day post-treatment period. Chronic ICV ghrelin infusion increased food intake (22±3 to 26±1g/day) leading to ∼50g body weight gain. BP fell slightly during ghrelin infusion while HR decreased by ∼26bpm. In control animals BP and HR increased modestly. ICV Ghrelin infusion caused a 50% reduction in sympathetic tone to the heart but did not alter BRS. We also tested if the depressor responses to ICV ghrelin infusion were enhanced in spontaneously hypertensive rats (SHR) due to their high basal sympathetic tone. However, we observed similar BP and HR responses compared to normotensive rats. These results indicate that ghrelin, acting via direct actions on the CNS, has a sustained effect to lower HR and a modest impact to reduce BP in normotensive and hypertensive animals despite increasing appetite and body weight.