ALTERATIONS IN SMALL ARTERIOLES PRECEDE CHANGES IN LIMB SKELETAL-MUSCLE AFTER MYOCARDIAL-INFARCTION

We tested the hypothesis that alterations in arterioles in locomotor s keletal muscles in rats with myocardial infarction (MI), but before de velopment of congestive heart failure (CHF), precede structural and fu nctional changes commonly observed in limb muscle in association with CHF. Resting diameters of third- (A3) and fourth-order arterioles (A4) in extensor digitorum longus (EDL) muscle were significantly smaller in rats with nonfailing small and medium-sized MI compared with contro l animals. Dilation of A4 in response to 10(-4) M adenosine was signif icantly attenuated in both groups (P < 0.05), whereas dilation of A3 w as unaltered. Microvessels from both groups of infarcted rats constric ted to all doses of acetylcholine (10(-9), 10(-8), and 10(-7) M) and s howed a significantly exaggerated vasoconstrictor response to norepine phrine (10(-9), 10(-8), and 10(-7) M) compared with microvessels in co ntrol rats (P < 0.05). Peak isometric tension of combined tibialis ant erior and EDL muscles and muscle fatigue (final/peak tension x 100), m easured during 5-min isometric supramaximal twitch contractions at 4 H z, were similar in control and MI rats (218 +/- 7 vs. 213 +/- 15 g/g m uscle and 52 +/- 1 vs. 51 +/- 9%, respectively; n = 5 for both). There was also no difference with respect to the proportion of oxidative fi bers or capillary-to-fiber ratios. Our results indicate that, in rats with left ventricular dysfunction but without failure, decreased diame ter and perturbations in reactivity of small arterioles precede altera tions in skeletal muscle performance often seen at a later date in ass ociation with CHF. These findings are consistent with the notion of ab errant endothelial and smooth muscle function and may contribute to th e maintenance of blood pressure after MI but before CHF.