Growth hormone secretagogue receptor deficiency in mice protects against obesity-induced hypertension

Harris, Louise E.; Morgan, David G.; Balthasar, Nina

Abstract

Growth hormone secretagogue receptor (GHS-R) signaling has been associated with growth hormone release, increases in food intake and pleiotropic cardiovascular effects. Recent data demonstrated that acute GHS-R antagonism leads to increases in mean arterial pressure mediated by the sympathetic nervous system in rats; a highly undesirable effect if GHS-R antagonism was to be used as a therapeutic approach to reducing food intake in an already obese, hypertensive patient population. However, our data in conscious, freely moving GHS-R deficient mice demonstrate that chronic absence of GHS-R signaling is protective against obesity-induced hypertension. GHS-R deficiency leads to reduced systolic blood pressure variability (SBPV); in response to acute high-fat diet (HFD)-feeding, increases in the sympathetic control of SBPV are suppressed in GHS-R KO mice. Our data further suggest that GHS-R signaling dampens the immediate HFD-mediated increase in spontaneous baroreflex sensitivity. In diet-induced obesity, absence of GHS-R signaling leads to reductions in obesity-mediated hypertension and tachycardia. Collectively, our findings thus suggest that chronic blockade of GHS-R signaling may not result in adverse cardiovascular effects in obesity.

Citation

Harris, L. E., Morgan, D. G., & Balthasar, N. (2014). Growth hormone secretagogue receptor deficiency in mice protects against obesity-induced hypertension. Physiological Reports, 2(3), e00240-?. https://doi.org/10.1002/phy2.240

• Journal Article Type: Article
• Acceptance Date: Jan 26, 2014
• Online Publication Date: Mar 3, 2014
• Publication Date: 2014-03
• Publicly Available Date: May 26, 2023
• Journal: Physiological Reports
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 2
• Issue: 3
• Pages: e00240-?
• DOI: https://doi.org/10.1002/phy2.240
• Keywords: diet-induced obesity, ghrelin, growth hormone secretagogue receptor, hypertension
• Publisher URL: https://doi.org/10.1002/phy2.240