Acute administration of acyl, but not desacyl ghrelin, decreases blood pressure in healthy humans

Abstract

Objective: To compare the effects of acyl ghrelin (AG) and desacyl ghrelin (DAG) on blood pressure (BP), heart rate (HR) and other autonomic parameters in healthy humans and to elucidate the hormonal mechanisms through which AG could exert its cardiovascular effects.

Design: Seventeen healthy participants underwent frequent monitoring of systolic (sBP) and diastolic blood pressure (dBP), HR, respiratory rate (RR) and body surface temperature (Temp) during continuous infusion of AG, DAG, combined AG + DAG or saline control before and during an IV glucose tolerance test on 4 separate days. Plasma catecholamines, renin and aldosterone levels were also measured. Differences in outcome measures between treatment groups were assessed using mixed-model analysis.

Results: Compared to the saline control, AG and combined AG + DAG infusions decreased sBP, dBP, mean arterial blood pressure (MAP), HR and Temp. In contrast, DAG infusion did not alter BP, RR or Temp, but did decrease HR. The AG and AG + DAG infusions also raised plasma aldosterone levels compared to saline (P < 0.001) without affecting renin or catecholamine levels.

Conclusions: The decrease in BP, HR, RR and Temp with AG infusion suggests mediation through the autonomic nervous system. The lack of response to DAG suggests that these autonomic effects require activation of the ghrelin receptor.

Figure 1. Blood Pressure, Heart Rate, Respiratory Rate Responses to Drug Infusion

Systolic blood pressure (sBP; Fig. 1A), diastolic blood pressure (dBP; Fig. 1B), mean arterial pressure (MAP; Fig. 1C), heart rate (HR; Fig. 1D), body surface temperature (Temp; Fig. 1E), and respiratory rate (RR; Fig. 1F) values during acyl ghrelin (AG;1 μg/kg/h), desacyl ghrelin (DAG; 4 μg/kg/h), combined (COM) AG (1 μg/kg/h) and DAG (4 μg/kg/h), or saline infusions between 0 and 210 minutes in healthy men and women. An intravenous glucose tolerance test (IVGTT) was administered between 30 and 210 min after the peptide infusions began. Blood pressure is presented in mmHg, heart rate as beats per minute (bpm), Temp as °C, and RR as breaths per minute (breaths/min).

Figure 2. Study 1 Effects of AG and DAG on Catecholamines, Renin, and Aldosterone

Plasma aldosterone (pg/mL; Fig. 2A), renin (μIU/mL; Fig. 2B), norepinephrine (NE in pg/mL; Fig. 2C), and epinephrine (Epi in pg/mL; Fig. 2D) concentrations during a 210-min infusion of saline, acyl ghrelin (AG), desacyl ghrelin (DAG), or combined AG + DAG in 10 healthy men and women. The NE and Epi concentrations were only assayed until the 120 minute time point. An intravenous glucose tolerance test (IVGTT) was also performed between 30 and 210 min after the peptide infusions began. The area under the curve (AUC) is shown for NE, Epi, renin, and aldosterone.