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

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.