Aging and menopause are associated with decreased nitric oxide bioavailability due to reduced L-arginine (L-ARG) levels contributing to endothelial dysfunction (ED). ED precedes arterial stiffness and hypertension development, a major risk factor for cardiovascular disease. This study investigated the effects of L-citrulline (L-CIT) on endothelial function, aortic stiffness, and resting brachial and aortic blood pressures (BP) in hypertensive postmenopausal women. Twenty-five postmenopausal women were randomized to 4 weeks of L-CIT (10 g) or placebo (PL). Serum L-ARG, brachial artery flow-mediated dilation (FMD), aortic stiffness (carotid-femoral pulse wave velocity, cfPWV), and resting brachial and aortic BP were assessed at 0 and 4 weeks. L-CIT supplementation increased L-ARG levels (Δ13 ± 2 vs. Δ−2 ± 2 µmol/L, p < 0.01) and FMD (Δ1.4 ± 2.0% vs. Δ−0.5 ± 1.7%, p = 0.03) compared to PL. Resting aortic diastolic BP (Δ−2 ± 4 vs. Δ2 ± 5 mmHg, p = 0.01) and mean arterial pressure (Δ−2 ± 4 vs. Δ2 ± 6 mmHg, p = 0.04) were significantly decreased after 4 weeks of L-CIT compared to PL. Although not statistically significant (p = 0.07), cfPWV decreased after L-CIT supplementation by ~0.66 m/s. These findings suggest that L-CIT supplementation improves endothelial function and aortic BP via increased L-ARG availability.

ObjectivePostmenopausal women (post-MW) have greater risk of heart failure due to aortic pulsatile overload on the left ventricle associated with increased backward wave pressure (Pb). Post-MW have exaggerated peripheral blood pressure (BP) response to exercise mediated by metaboreflex (postexercise muscle ischemia [PEMI]) overactivation. Increased forward wave pressure (Pf) and Pb are determinants of aortic pulse pressure (PP) during isometric handgrip exercis (IHG) in young adults. We hypothesized that aortic PP and pressure wave responses to PEMI are augmented in nonhypertensive post-MW compared with premenopausal women (pre-MW).MethodsAortic BP, Pf, Pb, and reflection magnitude were assessed at rest and during IHG and PEMI by applanation tonometry in 15 pre-MW and 16 post-MW.ResultsAortic systolic BP during PEMI similarly increased in both groups. The increase in diastolic BP was lower in post-MW (post-MW Δ6 ± 2 vs pre-MW Δ11 ± 2 mm Hg, P < 0.05). Aortic PP (post-MW Δ8 ± 2 vs pre-MW Δ3 ± 2), Pf (post-MW Δ6 ± 1 vs pre-MW Δ0 ± 1), and Pb (post-MW Δ5 ± 1 vs pre-MW Δ2 ± 1) augmented during PEMI in post-MW (P < 0.05 for all), but not in pre-MW. Reflection magnitude increased during PEMI only in pre-MW (pre-MW Δ7 ± 2 vs post-MW Δ-1 ± 2, P < 0.05) due to concurrent increases in Pf and Pb in post-MW.ConclusionsEven in nonhypertensive postmenopausal women, increases in Pf and Pb and decrease in aortic DBP are important factors that contribute to the augmented aortic PP response to PEMI.

Postmenopausal women (PMW) may experience endothelial dysfunction associated with arginine (ARG) deficiency relative to asymmetric dimethylarginine (ADMA) caused by oxidative stress. Endothelial dysfunction contributes to increased blood pressure (BP) responsiveness to sympathoexcitation induced by the cold pressor test (CPT). We investigated the effects of citrulline alone (CIT) and combined with the antioxidant glutathione (CIT+GSH) on vascular function. Forty-four healthy PMW were randomized to CIT (6 g), CIT+GSH (2 g + 200 mg: Setria®) or placebo (PL) for 4 weeks. Brachial artery flow-mediated dilation (FMD), aortic stiffness (pulse wave velocity, PWV), brachial and aortic BP reactivity to CPT, and serum fasting blood glucose (FBG), ARG, and ARG/ADMA ratio were measured. Baseline FBG was higher in CIT+GSH vs. PL. FMD increased after CIT+GSH vs. PL (p < 0.05). CIT and CIT+GSH increased ARG/ADMA (p < 0.05), but did not affect aortic PWV. CIT+GSH attenuated the brachial and aortic systolic BP and mean arterial pressure (MAP) responses to CPT vs. PL and CIT (p < 0.05). The improvements in FMD were related to baseline FMD (r = −0.39, p < 0.05) and aortic MAP response to CPT (r = −0.33, p < 0.05). This study showed that CIT+GSH improved FMD and attenuated systolic BP and MAP reactivity in PMW. Although CIT increased ARG/ADMA, it did not improve FMD in healthy PMW.

Recently, it has been reported that dietary supplementation with grape seed extract (GSE) ameliorates endothelial function and increase nitric oxide (NO) bioavailability. Thus, we investigated if elevated blood pressure and aortic stiffness (AoS) characterized in obese individuals are attenuated following acute GSE supplementation. Twenty men (obese510; normal body weight (NBW)510) participated in this study. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), and AoS were compared 2 h after ingestion of GSE or placebo (PL) on different days, 1 wk apart. Compared with the PL, GSE supplementation significantly decreased SBP (NBW: 10364 vs. 9963 mmHg; obese: 11863 vs. 11265 mmHg) and MAP (NBW: 7562 vs. 7262 mmHg; obese: 8663 vs. 8463 mmHg) in both groups, while there were no differences in HR, SV, DBP, TPR, and AoS. GSE supplementation significantly decreased CO in only obese group. In NBW group, TPR tended to be decreased, but there was no significant difference. Our study suggests that acute supplementation with GSE reduced both SBP and MAP via a reduction in CO in obese individuals and decreased peripheral vasoconstriction in NBW group.