Department of Medicine, Epidemiology, Vanderbilt University School of Medicine, Nashville, TN, 37212-8802, USA.
Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Room 536 Robinson Research Building, Nashville, TN, 37212-8802, USA.
Clin Auton Res. 2024 Aug;34(4):427-436. doi: 10.1007/s10286-024-01050-3. Epub 2024 Aug 1.
Hypertension is one of the major causes of cardiovascular morbidity and mortality in the USA and disproportionately affects Black women. Endothelial-derived nitric oxide (eNO) substantially regulates blood pressure in humans, and impaired NO-mediated vasodilation has been reported in the Black population. Previous studies using an NO synthase inhibitor, N-monomethyl-L-arginine (L-NMMA) did not fully determine the NO contribution to blood pressure because of baroreflex buffering. Therefore, in the present study we used trimethaphan, a ganglionic blocker, to inhibit baroreflex buffering and study NO modulation of blood pressure in Black women during L-NMMA infusion.
L-NMMA at doses of 250 μg/kg per minute was infused in combination with trimethaphan at doses of 4 mg/min to eliminate baroreflex mechanisms. Heart rate (HR) was obtained with continuous electrocardiogram monitoring, and continuous blood pressure was measured with the volume clamp method. The increase in systolic blood pressure (SBP) during both infusions was used to estimate the contribution of NO to blood pressure.
Ten Black (age range 30-50 years, body mass index [BMI] 30-45 kg/m), and nine White women (age range 30-50 years, body mass index 30-45 kg/m) were enrolled in this study. During autonomic blockade, there was no difference in the decrease in SBP between Black and White women (- 20 ± 16.45 vs. - 24 ± 15.49 mm Hg, respectively; P = 0.659). When autonomic blockade was combined with L-NMMA, Black women had a significant increase in SBP compared to White women (54 ± 13.62 vs. 39 ± 09.64 mm Hg, respectively; P = 0.022, respectively).
Autonomic blood pressure regulation was similar between Black and White women. However, NO contribution to blood pressure was significantly greater in Black women compared to White women.
ClinicalTrials.gov: NCT01122407.
高血压是美国心血管发病率和死亡率的主要原因之一，且不成比例地影响黑人女性。内皮衍生的一氧化氮（eNO）在很大程度上调节人类的血压，而黑人人群中已经报道了一氧化氮介导的血管舒张功能受损。先前使用一氧化氮合酶抑制剂 N-单甲基-L-精氨酸（L-NMMA）的研究并未完全确定一氧化氮对血压的贡献，因为存在压力反射缓冲。因此，在本研究中，我们使用三甲噻酚，一种神经节阻滞剂，来抑制压力反射缓冲，并在黑人女性中研究 L-NMMA 输注期间一氧化氮对血压的调节作用。
以 250μg/kg/min 的剂量输注 L-NMMA，同时以 4mg/min 的剂量输注三甲噻酚，以消除压力反射机制。通过连续心电图监测获得心率（HR），并使用容积钳法连续测量血压。两种输注过程中收缩压（SBP）的升高用于估计一氧化氮对血压的贡献。
本研究纳入了 10 名黑人（年龄范围 30-50 岁，体重指数 [BMI] 30-45kg/m）和 9 名白人女性（年龄范围 30-50 岁，体重指数 30-45kg/m）。在自主神经阻断期间，黑人女性和白人女性 SBP 的下降没有差异（分别为-20±16.45mmHg 和-24±15.49mmHg；P=0.659）。当自主神经阻断与 L-NMMA 联合使用时，黑人女性的 SBP 与白人女性相比显著升高（分别为 54±13.62mmHg 和 39±09.64mmHg；P=0.022）。
黑人女性和白人女性的自主血压调节相似。然而，与白人女性相比，黑人女性的血压中一氧化氮的贡献明显更大。
ClinicalTrials.gov：NCT01122407。
