Mechanisms Underlying Obesity‐Related Hypertension: An Experimental Weight Gain Study in Humans

Abstract

BackgroundThe association between body size and blood pressure (BP) is well recognised. However, not all overweight individuals have elevated BP suggesting that important adaptive mechanisms are present in some. Cardiac output (CO, a key determinant of BP, is elevated in young overweight individuals, but is not associated with the level of BP. However, peripheral vascular resistance (PVR) is associated with the level of BP in these individuals, suggesting that the ability to modulate PVR in response to increased CO is important.ObjectiveWe hypothesized that weight gain increases CO in healthy humans and that the ability of the peripheral vasculature to adapt to this increase determines BP. Therefore, we undertook an exploratory study of experimental weight gain in healthy young adults.MethodsSixteen healthy non‐obese males were recruited (mean±SD age 29±6 years). All participants were overfed approximately 1000kcal/day, alongside their normal diet, for 6–8 weeks, until a weight gain of 5kg was achieved and held stable for at least 1 week. Detailed anthropometric characteristics, BP, CO and PVR were assessed at baseline and at completion of the overfeeding intervention.ResultsOverfeeding resulted in a significant increase in body weight (6.11±3.08kg, P<0.001), lean mass (3.61±3.40kg, P=0.001) and fat mass (2.64±2.89kg, P=0.002). The increases in systolic BP (2±9mmHg) and diastolic BP (2±6mmHg) were not significant (P<0.2 for both) and the increase in heart rate was of borderline significance (5±10bpm, P=0.055). As hypothesised, there was a significant increase in cardiac output (0.81±1.35L/min, P=0.031), which was accompanied by a decrease in PVR (129±205dynes.sec.cm5, P=0.024). Dichotomising individuals on the basis of a systolic BP response to weight gain of ≥5mmHg (BP responders) revealed small differences vs non‐responders in the change in CO (+1.34±0.99L/min vs +0.4±1.50L/min) and PVR (−111±142 dynes.sec.cm5 vs −143±251 dynes.sec.cm5), although neither comparison was statistically significant.ConclusionsModest weight gain in healthy, non‐obese men is associated with an increase in both lean and fat tissue mass. A compensatory reduction in PVR in response to elevated cardiac output is likely to explain the lack of change in BP. Examining ‘responders’ versus ‘non responders’ in terms of BP change in response to weight gain is likely to provide useful insights into obesity‐associated hypertension in a larger trial.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.