Obesity and hypertension share a well known association. However, the mechanisms underlying their relationship are not well understood. Our goal was to assess the feasibility of a longitudinal, interventional weight gain study with detailed cardiovascular measurements in humans. Sixteen healthy, normotensive, young, male volunteers (28 ± 7 years) were enrolled. Body composition, biochemical and cardiovascular data were obtained at baseline, and after an 8-week period of overfeeding (800-1000 kcal/day). Blood pressure (BP), cardiac output (CO) and peripheral vascular resistance (PVR) were determined, as were the minimum forearm vascular resistance (MFVR), forearm blood flow (FBF) response to mental stress and heart rate variability (HRV) parameters. Overfeeding resulted in a median weight gain of 5.6 kg [interquartile range (IQR) 4.6-6.4 kg; P < 0.001]. Seated systolic and diastolic BP were significantly increased by 10 ± 9 and 4 ± 6 mmHg, respectively, after weight gain ( P < 0.001 and P = 0.011, respectively). CO also increased and PVR decreased significantly as a result of weight gain ( P = 0.032 and P = 0.044, respectively). MFVR was also significantly decreased after weight gain ( P = 0.023). The FBF response to mental stress was blunted significantly ( P = 0.002), and sympathovagal balance and responsiveness to orthostatic challenge altered moderately after weight gain. Our overfeeding regimen resulted in moderate weight gain and significant increases in BP. An increase in CO is likely to be the dominant mechanism underlying the observed BP changes, with decreases in PVR partially compensating for these effects. Experimental weight gain, coupled with detailed cardiovascular phenotyping, is a feasible model to examine potential mechanisms underlying obesity-associated hypertension in young adults.
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