Valsartan therapy in heart failure after myocardial infarction: The role of endothelial dependent vasorelaxation

Angiotensin II receptor blockade (ARB) increases vasorelaxation in heart failure by enhancing endothelial nitric oxide (NO). To determine the effects of valsartan on NO-mediated peripheral vascular function after myocardial infarction (MI), we treated adult male Sprague-Dawley rats immediately after MI with valsartan for 3 weeks (sham, n = 10; MI, n = 11) and 6 weeks (sham, n = 6; MI, n = 8). At both time points, valsartan lowered (P < 0.05) left ventricular (LV) systolic pressure (103 ± 4 and 107 ± 4 vs. 93 ± 3 and 85 ± 4 mm Hg, respectively) and LV end-diastolic pressure (25 ± 1 and 25 ± 2 to 13 ± 2 and 18 ± 3 mm Hg, respectively). Valsartan lowered (P < 0.05) LV dP/dt only at 6 weeks (4676 ± 168 and 4503 ± 232 vs. 4539 ± 281 and 3372 ± 417 mm Hg/sec); valsartan shortened (P < 0.05) the time constant of LV relaxation or tau only at 3 weeks (24.2 ± 1.8 and 26.5 ± 2.3 vs. 20.1 ± 0.7 and 23.8 ± 1.4 msec). At 6 weeks, the vasorelaxation response to acetycholine in aortic rings was decreased (P < 0.05) with MI and improved at acetycholine doses (10, 10, and 10; P < 0.06) with valsartan. Endothelial nitric oxide synthase (eNOS) protein was undetectable in aortic tissue from valsartan treated rats or from aortic tissue incubated with valsartan (2.5, 25, and 50 mg/mL). These data suggest that valsartan improves cardiac function after MI by modulating LV remodeling, decreasing LV end-diastolic pressure, and enhancing both LV diastolic and endothelial function. These effects are mediated, in part, by NO but upregulation of eNOS may not be required for improved systemic endothelial function in heart failure.