Hypertension increases oxidative stress, which can impair myocardial microvascular function and integrity. However, it is yet unclear whether long-term
antioxidant intervention in early
hypertension would preserve myocardial perfusion and vascular permeability responses to challenge. Pigs were studied after 12 weeks of
renovascular hypertension without (n=8) or with daily supplementation of
antioxidants (100 IU/kg
vitamin E and 1 g
vitamin C, n=6), and compared with normal controls (n=7). Myocardial perfusion and microvascular permeability were measured in vivo by electron beam computed tomography before and after 2 cardiac challenges (intravenous
adenosine and
dobutamine). Basal left ventricular muscle mass was also obtained. Mean arterial pressure was significantly increased in both groups of hypertensive animals (without and with
antioxidants, 123+/-9 and 126+/-4 mm Hg, respectively, versus normal, 101+/-4 mm Hg; both P<0.05), but muscle mass was not different among the groups. The impaired myocardial perfusion response to
adenosine observed in hypertensives (normal, +51+/-14%; P<0.05 versus baseline;
hypertension, +14+/-15%; P=0.3 versus baseline) was preserved in hypertensive pigs that received
antioxidants (+44+/-15%; P=0.01 compared with baseline). Long-term
antioxidant intervention also preserved subendocardial microvascular permeability responses in
hypertension. On the other hand,
antioxidant intervention had little effect on the
hypertension-induced myocardial vascular dysfunction observed in response to
dobutamine. This study demonstrates that the impaired myocardial perfusion and permeability responses to increased cardiac demand in early
hypertension are significantly improved by long-term
antioxidant intervention. These results support the involvement of oxidative stress in myocardial vascular dysfunction in
hypertension and suggest a role for
antioxidant strategies to preserve the myocardial microvasculature.