Effects Of Enalapril On Interstitial PO2 And Contractile Function In The Edl Of Diabetic Rats

Abstract

Angiotensin converting enzyme inhibitors (ACEi) are standard of care for Type I diabetics. ACEi play a role in preventing diseases such as heart failure, kidney disease, and diabetic neuropathy. Diabetes causes changes within skeletal muscle that alter the balance between oxygen delivery (QO2) and oxygen consumption (VO2) as reflected by changes in the interstitial PO2 (PiO2). PURPOSE: To determine if treatment with the ACEi enalapril would attenuate the effects of diabetes on PiO2 and contractile function in the rat extensor digitorum longus muscle (EDL). METHODS: Female Sprague-Dawley rats (n=33, 282 ± 3 g) were randomly assigned to control (C, 11), diabetic (D, 11), or enalapril-treated diabetic groups (E, 11). Diabetes was induced using streptozotocin (50 mg/kg) and confirmed by urine glucose (>2000 mg/dl). The E group then began a 7 wk treatment regimen of enalapril in their drinking water (15 mg/kg/d). Rats were anesthetized (sodium pentobarbital, 50 mg/kg) and the EDL was exposed and connected to a muscle tension analyzer. PiO2 (phosphorescent quenching) and contractile function were assessed at rest and during the transition to steady-state contractions (1 Hz, 6V). RESULTS: D rats weighed less than C (D, 266 ± 5 vs 305 ± 8 g) and showed atrophy of the EDL (127 ± 10 vs 177 ± 8 mg), and E rats were not different from D (285 ± 10 g and 138 ± 9 mg). Enalapril resulted in a marked reduction in mean arterial pressure (C, 116 ± 2; D, 108 ± 2; E, 91 ± 2 mmHg). Resting PiO2 was lower in D compared to C (24 ± 1 vs. 28 ± 1 mmHg). At the onset of contractions, PiO2 fell more rapidly in D than C (i.e., faster on-kinetics) as reflected by the shorter mean response time (13 ± 2 vs. 22 ± 2 s). Resting PiO2 in E (30 ± 2 mmHg) was greater than D, and on-kinetics were slower (MRT, 19 ± 2 s) and not different from C. Peak twitch tension (per muscle mass) was greater in D compared to C (1.78 ± 0.04 vs. 1.36 ± 0.04 N/g), while twitch tension in E was similar to D (1.88 ± 0.04 N/g). Fatigue was greater in both the D and E groups relative to C (C, 5 ± 1; D, 12 ± 1, E, 11 ± 1 %). CONCLUSIONS: These results confirm previous reports of a diabetes-induced imbalance between QO2 and VO2 at rest and during contractions in diabetic rats. ACEi treatment prevented these changes but did not improve contractile function or fatigue resistance. These results support the notion that ACEi treatment improves the matching of QO2 and VO2 to skeletal muscle. (Supported by Graduate Program Committee, KCOM-ATSU.)