AGE-DEPENDENT AUGMENTATION OF CARDIAC ENDOTHELIAL NOS IN A GENETIC RAT MODEL OF HEART-FAILURE

Alterations in nitric oxide (NO) biosynthesis in the heart have been i mplicated in the pathophysiology of heart failure. We compared changes in cardiac nitric oxide synthase (NOS) activity and expression in gen etically heart failure-prone (SHHF) rats at 6, 12, and 18 mo of age wi th those in age-matched spontaneously hypertensive (SHR) and Sprague-D awley (SD) rats. Systolic blood pressure was significantly higher in S HHF and SHR rats compared with SD rats; however, it declined with age in SHHF rats only. Left. ventricular mass increased with age in SHR an d SHHF, but not in SD rats. Plasma nitrate and nitrite level was eleva ted in SHHF and SHR rats at 18 mo only. In left ventricular homogenate s from SHHF rats, Ca2+- dependent NOS activity increased markedly with age and was accompanied by enhanced expression of endothelial NOS (eN OS). In contrast, SHR rats showed a much smaller increase in Ca2+-depe ndent NOS activity over time without changes in eNOS expression; neith er parameter was altered with age in SD rats. Ca2+-independent NOS act ivity was not detected in any heart. This is the first report of a uni que alteration in myocardial NOS activity in hypertensive rats genetic ally prone to heart failure.