Differences in vascular nitric oxide and endothelium-derived hyperpolarizing factor bioavailability in blacks and whites

Abstract

Objective: Abnormalities in nitric oxide (NO) bioavailability have been reported in blacks. Whether there are differences in endothelium-derived hyperpolarizing factor (EDHF) in addition to NO between blacks and whites and how these affect physiological vasodilation remain unknown. We hypothesized that the bioavailability of vascular NO and EDHF, at rest and with pharmacological and physiological vasodilation, varies between whites and blacks.

Approach and results: In 74 white and 86 black subjects without known cardiovascular disease risk factors, forearm blood flow was measured using plethysmography at rest and during inhibition of NO with N(G)-monomethyl-L-arginine and of K(+) Ca channels (EDHF) with tetraethylammonium. The reduction in resting forearm blood flow was greater with N(G)-monomethyl-L-arginine (P=0.019) and similar with tetraethylammonium in whites compared with blacks. Vasodilation with bradykinin, acetylcholine, and sodium nitroprusside was lower in blacks compared with whites (all P<0.0001). Inhibition with N(G)-monomethyl-L-arginine was greater in whites compared with blacks with bradykinin, acetylcholine, and exercise. Inhibition with tetraethylammonium was lower in blacks with bradykinin, but greater during exercise and with acetylcholine.

Conclusions: The contribution to both resting and stimulus-mediated vasodilator tone of NO is greater in whites compared with blacks. EDHF partly compensates for the reduced NO release in exercise and acetylcholine-mediated vasodilation in blacks. Preserved EDHF but reduced NO bioavailability and sensitivity characterizes the vasculature in healthy blacks.

Clinical trial registration url: http://clinicaltrials.gov/. Unique identifier: NCT00166166.

Keywords: African Americans; EDHF; exercise; nitric oxide; vasodilation.

Figure 1

Aspirin (975mg) was administered 1hour prior to commencement of the study. In separate protocols, FBF measurements were performed after either intra-arterial infusions of bradykinin (100, 200 and 400 ng/min), or intra-arterial acetylcholine (7.5, 15 and 30 μg/min), or handgrip exercise (15%, 30% and 45% of maximum grip strength) followed by endothelium-independent vasodilation with sodium nitroprusside (1.6, 3.2 μg/min). Measurements were repeated after NO blockade with L-NMMA, K⁺_Ca channel blockade with TEA, and after combined blockade with L-NMMA and TEA.

Figure 2

Change in resting FBF and FVR in response to (a) L-NMMA in 42 healthy AA and 46 white subjects, (b) in response to TEA in 41 healthy AA and 45 white subjects, and (c) to combined L-NMMA and TEA infusions in 38 healthy AA and 46 white subjects. Data is shown as mean ± SEM.

Figure 3

Forearm vasodilator response to (a) bradykinin, (b) acetylcholine, (c) hand-grip exercise, and (d) sodium nitroprusside in healthy African American and Caucasian subjects. Data shown as mean + SEM. Data shown as mean + SEM. *p<0.05; **p<0.01; ***p<0.001

Figure 4

Vasodilation with bradykinin before and after inhibition with (a) L-NMMA or (b) TEA in African American and Caucasian subjects. Change in FBF and FVR in response to bradykinin after inhibition with (a) L-NMMA in AA (n=34) and white (n=38) subjects, and (b) with TEA in AA (n=32) and white (n=28) subjects. Data is shown as mean ± SEM. *p<0.0001

Figure 5

Vasodilation with acetylcholine before and after inhibition with L-NMMA or TEA in African Americans and Caucasians subjects. Change in FBF and FVR in response to acetylcholine after inhibition with (a) L-NMMA in AA (n=26) and white (n=17) subjects, and (b) after inhibition with TEA in African American (n=26) and Caucasian (n=17) subjects. Data is shown as mean ± SEM. *p<0.01; **p<0.001; ***p<0.0001

Figure 6

Vasodilation with forearm exercise before and after inhibition with (a) L-NMMA or (b) TEA in African American and Caucasian subjects. Change in FBF and FVR in response to increasing handgrip exercise (15, 30 and 45% of maximal handgrip) alone and (a) after L-NMMA, 16μmol/min) in AA (n=24) and Caucasian (n=19) subjects, and (b) after TEA in AA (n=24) and Caucasian (n=19) subjects. Data shown as mean ± SEM. *p=0.01; **p<0.0001