Cardiac Microvasculature in DOCA-Salt Hypertensive Rats

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Abstract
—The cardiac abnormalities associated with hypertension include left ventricular hypertrophy and vascular changes. The latter may affect the cardiac microvasculature and predispose to myocardial ischemia. To test the hypothesis that endothelin-1 contributes to changes in the microcirculation of the heart, we studied cardiac microvessels of the deoxycorticosterone acetate–salt (DOCA-salt) model of hypertension in the rat, in which the endothelin system is activated, and the effect of the endothelin-A (ET A ) subtype–selective endothelin receptor antagonist A-127722. A-127722 (30 mg · kg −1 · d −1 ) was administered for 4 weeks. Arterioles (≤20 μm in lumen diameter) were identified in the myocardium by use of immunolabeling with an anti–smooth muscle α-actin antibody, and capillaries with an anti-laminin antibody with nuclear counterstaining by nuclear fast red. Systolic blood pressure was 103±1.6 mm Hg in unilaterally nephrectomized rats (UniNx), 202±3.2 mm Hg in DOCA-salt ( P A antagonist–treated DOCA-salt ( P P A antagonist–treated DOCA-salt ( P P A antagonist–treated DOCA-salt ( P A receptor antagonism. This suggests a role for endothelin-1 in cardiac arteriolar growth and capillary rarefaction, which may have pathophysiological implications by contributing to myocardial ischemia in hypertension.