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.